A method for determination of the genetic predisposition of a subject to sports development in sports disciplines, a method for individualised management of athletic training of a subject, a method for individualised management of dietary supplementation of a subject, and a method for injury susceptibility prediction of a subject

Abstract

The present invention relates to a method for determination of the genetic predisposition of a subject to sports development in sports disciplines. The method includes the steps of evaluation of a genetic sample of the subject for the presence of polymorphisms in genes determining the formation of physical traits associated with the subject sports development in sports disciplines to obtain a polygenic profile, analysis of polygenic profile to identify genetic variants responsible for predisposition to sports disciplines, and determination of the subject predisposition to practice a sports discipline based on the polygenic profile obtained. Moreover, the present invention relates to a method for individualised management of sports training of a subject, the present invention also relates to a method for individualised management of dietary supplementation of a subject, and the present invention also relates to a method for injury susceptibility prediction of a subject.

Description

DescriptionTitle of Invention: A method for determination of the genetic predisposition of a subject to sports development in sports disciplines, a method for individualised management of athletic training of a subject, a method for individualised management of dietary supplementation of a subject, and a method for injury susceptibility prediction of a subject

[0001] The present invention relates to a method for determination of the genetic predisposition of a subject to sports development in sports disciplines. Moreover, the present invention relates to a method for individualised management of sports training of a subject, the present invention also relates to a method for individualised management of dietary supplementation of a subject, and the present invention also relates to a method for injury susceptibility prediction of a subject Technical Field

[0002] The methods disclosed in the present application are based on the analysis of the genetic profiles of a subject Genetic testing is increasingly used to evaluate people's physical predisposition to sports development in many sports disciplines. Based on the evaluation of a genetic sample and analysis of a subject's genetic profile, predicting a subject's potential to thrive in a particular sports discipline is possible. Hence, with genetic testing, there is a possibility of evaluating whether a given subject exhibits the genetic potential to become an elite athlete. Such testing can therefore be incorporated into the selection process of a cadre of athletes in many sports disciplines. Moreover, based on the genetic profile obtained, it is possible to plan and manage the subject sports training, providing for the need to develop specific physical traits depending on the sports discipline practised and natural predispositions (i.e. anaerobic endurance, aerobic endurance, power). Based on the genetic profile, it is also possible to develop individualised dietary supplementation and predict the injury susceptibility of a subject. All these measures aim to improve a subject's sports development in sports disciplines.

[0003] Different variants of the same gene (genotypes) can determine the development of desirable physical traits in young athletes, making them a reliable predictor of the future success of an athlete. Nearly 300 genes are known at present, the variants of which can determine the development of specific physical and mental traits.Background Art

[0004] Methods for determination of genetic predisposition for sports development in sports disciplines and managing sports training are known.

[0005] Document W02004024947 discloses a method of predicting athletic performance in a subject based on the presence of one or more genetic variants in the ACTN3 genotype. In certain embodiments, screening is also conducted for the presence of genetic variants in the ACE genotype and the ADRA2A gene.

[0006] Document WO2020212936 discloses a method to predict the predisposition to an exercise performance trait in a human individual. The disclosed method is based on the evaluation of genetic variation in each of the following genes: ACTN3, COL5A1, MCT1, VEGF, HFE. Based on a polymorphism profile obtained and the value of the regression function, a human individual is classified given physical performance.

[0007] Document WO2011094815 discloses a method for identifying a genetic predisposition associated with exercise endurance. Polymorphisms in genes selected from the group consisting of ACE, ACTN3, ADBR2, AMPD1, CKM, EPAS1, GDF-8, HFE, NFATC4, NOS3, NRF2, PPARa, PPARS, PPARyCIA, PPARyCl, TFAM, UCP2, UCP3 and VEGF A are analysed.

[0008] Document CN103160597 discloses a method for prediction of bouncing potentials of excellent ice-snow sportsmen. The method uses polygenic profile analysis in the ACTN3 and ACE genes.

[0009] There are also known scientific publications on studies into the identification of genetic polymorphisms and their impact on sports performance. These studies are also used to design training programmes. For example, R. La Montagna et al (Journal of Cellular Physiology, 2019; 1-10) publication discloses that it is essential to study genetic variants in 5 genes: ACTN3, COL5A1, MCT1, VEGF and HFE. A. B. T. McAuley et al (European Journal of Sport Science, 2021) review article describes a study on the association of polymorphic variants in ACTN3 or ACE genes with athletic performance parameter.

[0010] Although methods for predicting physical predisposition for sports development in several sports disciplines are known, these methods still have some disadvantages and deficiencies, including inter alia a limited level of efficiency and reproducibility of prediction due to the number of genes tested and the limited number of subjects tested, which affects the unambiguity of the results obtained. Similar limitations exist for the methods for manage the individualised training of subjects, the dietary supplementation of subjects and the prediction of injury susceptibility.Summary of Invention

[0011] There is therefore a need to provide a method for determination of the genetic predisposition of a subject for sports development in sports disciplines, which willallow precise and effective identification of talent, particularly at a young age, in a particular sports discipline.

[0012] Moreover, there is a need to provide a method for individualised management of a subject's sports training based on a polygenic profile, wherein the method allows for identifying set of physical exercises that a subject should perform to improve their sports performance. Said method will allow for training to be optimised based on a subject's natural predisposition to develop specific physical traits.

[0013] Additionally, there is a need to provide a method for individualised management of dietary supplementation of a subject so that the diet can be suitably matched to the subject energy needs. There is also a need to provide a method for prediction of the injury susceptibility of a subject so that prevention against soft tissue injury of the subject can be achieved. The above-mentioned objects are achieved by a method for determination of genetic predisposition according to claim 1, a method for management of sports training according to claim 4, a method for management of dietary supplementation according to claim 12 and a method for injury susceptibility prediction according to claim 13. Preferable embodiments are the subject of the dependent claims.

[0014] The object of the invention is a method for determination of the genetic predisposition of a subject for sports development in sports disciplines. The method includes the following steps:

[0015] a) evaluation of a genetic sample of a subject for the presence of polymorphisms in genes determining the formation of physical traits associated with a subject sports development in sports disciplines to obtain a polygenic profile, wherein analysis of polymorphisms in genes selected from a group comprising ACTN3, ACE, HIFla, MCT1, UCP2, PPARA, AMPD1, COMT, MMP3 and / or COL5A1,

[0016] b) analysis of a polygenic profile to identify genetic variants responsible for predisposition to sports disciplines,

[0017] c) determination of the subject predisposition to practice a sports discipline based on the polygenic profile obtained.

[0018] Preferably, the object is a method in which the analysis of the genetic profile is performed using rough set analysis based on a machine learning algorithm, wherein the information system S is defined by the formula, where U indicates set of subjects, Q indicates set of values obtained from genetic tests, V indicates set of attribute values from set of and where f is aninformation function such thatfor eachwherein based on the values of set U, the indistinguishability relation is generated, defined by the formulaare the objects belonging to the product of the Cartesian set of universe,are each attribute from set is the information function for the pair: object x andattribute α, where specific pairs of objects are in a relation with each other NRS( B ) when they have the same values for all attributes from set B.

[0019] Preferably, the object is a method in which the resulting polygenic profile includes the following genetic variants:

[0020] In a further aspect, the object of the invention is a method for individualised management of the sports training of a subject including the following steps:

[0021] a) evaluation of a genetic sample of a subject for the presence of polymorphisms in genes selected from a group comprising ACTN3, ACE, HIFla, MCT1, UCP2, PPARA, AMPD1, COMT, MMP3 and / or COL5A1 to obtain a genetic profile,

[0022] b) analysis of a polygenic profile to identify genetic variants responsible for the development of physical-mental traits, wherein said traits include power, aerobic endurance, anaerobic endurance, muscular eccentric work, exercise energy, and the ability to process information under stress-inducing conditions,

[0023] c) definition of a training programme for the subject providing for the need to develop the listed physical traits based on the genetic profile obtained.

[0024] Preferably, the object is a method for individualised sports training management of a subject in which the polygenic profile obtained includes the following genetic variants:

[0025] Preferably, the object is a method for individualised sports training management of a subject in which, for training in power development, detection of polymorphisms is performed in genes selected from a group comprising ACTN3, ACE, HIFla, UCP2, and / or PPARA.

[0026] Preferably, the object is a method for individualised sports training management of a subject in which, for training in the development of aerobic endurance, detection of polymorphisms is performed in genes selected from a group comprising ACE, HIFla, and / or PPARA.

[0027] Preferably, the object is a method for individualised sports training management of a subject in which, for training in the development of anaerobic endurance, detection of polymorphisms is performed in the MCT1 gene.

[0028] Preferably, the object is a method for individualised sports training management of a subject in which, for training in eccentric muscle work, detection of polymorphisms is performed in genes selected from a group comprising ACTN3 and / or ACE.

[0029] Preferably, the object is a method for individualised sports training management of a subject in which, for training in exercise energy, detection of polymorphisms is performed in genes selected from a group comprising ACTN3, ACE and / or HIFla.

[0030] Preferably, an object is a method for individualised management of sports training of a subject in which, for training in information processing under stress-inducing conditions, detection of polymorphisms is performed in the COMT gene. In a further aspect, an object of the invention is a method for individualised management of dietary supplementation of a subject including the following steps:

[0031] a) evaluation of a genetic sample of a subject for the presence of polymorphisms in genes selected from a group comprising UCP2, PPARA, and / or AMPD1 to obtain a genetic profile,

[0032] b) analysis of a polygenic profile to identify genetic variants responsible for regulating ATP and reactive oxygen species levels in a subject,

[0033] c) determination of the dietary supplementation of the subject for mitochondria- directed antioxidants and D-ribose, xylitol and / or other sugars based on the genetic profile obtained.

[0034] In a further aspect, the object of the invention is a method for prediction of the injury susceptibility of a subject including the following steps:

[0035] a) evaluation of a genetic sample of a subject for the presence of polymorphisms in genes selected from a group comprising COL5A1 and / or MMP3 to obtain a genetic profile,

[0036] b) analysis of a polygenic profile to identify genetic variants responsible for susceptibility to soft tissue injury,

[0037] c) determination whether a subject is susceptible to soft tissue injuries.Description of Embodiments

[0038] Due to the invention, efficient, precise and reproducible identification of talents in sports disciplines fields is possible. The invention also provides a high versatility of identification given different sports fields, e.g. volleyball, football, basketball and others. Furthermore, the individualised training management according to the invention allows for optimise the sports performance of a subject by appropriately selecting a set of physical exercises given the training requirements, e.g. endurance training, power training and the like. The appropriate selection of training parameters will then lead to their adjustment given the sports discipline practised by the subject. Moreover, individualised management of a subject dietary supplementation will identify the need for dietary supplements given mitochondria-directed antioxidants and D-ribose, xylitol and / or other sugars, which will lead to the regulation of ATP level, which will then be matched for the sports discipline practised by the subject In addition, predicting the injury susceptibility of a subject will allow suitable training to be planned for the subject and provide the prevention of soft tissue injuries in the subject.

[0039] The method for determination of the genetic predisposition of a subject for sports development in sports disciplines according to the invention is divided into steps.

[0040] In the first step of the method according to the invention, a genetic sample taken from a subject is evaluated for the presence of polymorphisms in specifically selected genes. Thus, a polygenic profile of the subject is obtained.

[0041] Detection of polymorphisms is performed in genes selected from a group comprising ACTN3, ACE, HIFla, MCT1, UCP2, PPARA, AMPD1, COMT, MMP3 and / or COL5A1. In the preferred variant, detection is performed in each gene listed. Thismeans that the polygenic profile obtained by the method according to the invention consists of the listed genes, i.e. combinations of the listed genes. Detection can also be performed in one specifically identified gene or any combination of the listed genes. This means such variants are also disclosed herein where detection is performed in any combination of the listed genes.

[0042] In the second step of the method according to the invention, an analysis of the polygenic profile of the subject is performed to identify the genetic variants responsible for predisposition to the listed disciplines.

[0043] Preferably, the polygenic profile includes the following genetic variants within the genes listed:

[0044] This means that the result of the second step of the method according to the invention is the identification of a polygenic profile of a subject including genetic variants within the analysed genes, i.e. specific polymorphisms at specific positions in the analysed genes.

[0045] In the third step of the method according to the invention, the predisposition of a subject to practise a particular sports discipline is determined based on the polygenic profile obtained. Preferably, the mathematical analysis disclosed herein, in particular providing for machine learning, is used for this purpose. This means that the result of the third step of the method according to the invention is to indicate, based on the identified polygenic profile of the subject, for which sports discipline the subject is genetically predisposed. Thus, the method according to the invention provides for determination in which sports discipline a given subject should be developed in order to increase his or her chances of success in this sports discipline, e.g. by being included among the elite athletes.

[0046] The genetic variants within the genes listed above apply to all sports as defined in the present application.

[0047] The method for individualised management of a subject sports training is divided into steps.

[0048] In the first step of the method for training management according to the invention, a genetic sample taken from a subject is evaluated for the presence of polymorphisms in genes selected from the group comprising ACTN3, ACE, HIFla, MCT1, UCP2, PPARA, AMPD1, COMT, MMP3 and / or COL5A1 to obtain a genetic profile. Thus, the genetic profile of the subject is obtained.

[0049] In a preferred variant, detection is performed in each listed gene. This means that the genetic profile obtained by the method for training management according to the invention consists of the listed genes. Detection may also be performed in one specifically identified gene or any combination of the listed genes. This means such variants are also disclosed herein where detection is performed in any combination of the listed genes.

[0050] In the second step, an analysis of a genetic profile is performed to identify genetic variants specifically responsible for the physical traits development. The physical traits listed influence the development of a subject in sport, particularly in a given sports discipline. The physical traits listed include power, aerobic endurance, anaerobic endurance, muscular eccentric work, exercise energy, ability to process information under stress-inducing conditions.

[0051] Preferably, the genetic profile includes the following genetic variants within the genes listed:

[0052] In the third step of the method according to the invention, a training programme is defined for the subject providing for the need to develop the said physical traits based on the genetic profile obtained. Preferably, mathematical analysis, in particular providing for machine learning, is used for this purpose.

[0053] The method for training management according to the invention thus allows for determine and match the training programme of a subject by identifying which physical traits he / she should develop to improve his / her athletic performance. For example, the method for training management according to the invention allows for determine that a subject should be classified to perform intensive exercises related to the development of aerobic endurance due to identified genetic limitations in this respect

[0054] In the preferred variant, for training in power development, detection of polymorphisms is performed in genes selected from a group comprising ACTN3, ACE, HIFla, UCP2, and / or PPARA. In the more preferred variant, detection is performed in each gene listed, meaning that for power development training, detection of polymorphisms is performed in genes selected from the group consisting of ACTN3, ACE, HIFla, UCP2 and PPARA. In the most preferred variant, for power development training, detection includes genetic variants consisting of the following group:

[0055] In the preferred variant, for training in aerobic endurance development, detection of polymorphisms is performed in genes selected from a group comprising ACE, HIFla, and / or PPARA. In the more preferred variant, detection is performed in each gene listed, meaning that for training in aerobic endurance development, detection of polymorphisms is performed in genes selected from the group consisting of ACE, HIFla and PPARA. In the most preferred variant, for training in aerobic endurance development, detection includes genetic variants consisting of the following group:

[0056] In the preferred variant, for eccentric work training, detection of polymorphisms is performed in genes selected from the group comprising ACTN3, and / or ACE. In the more preferred variant, detection is performed in each gene listed, meaning that for eccentric work training, detection of polymorphisms is performed in genes selected from the group consisting of ACTN3 and ACE. In the most preferred variant, for eccentric work training detection includes genetic variants consisting of the following group:

[0057] In the preferred variant, for training in the development of anaerobic endurance, detection of polymorphisms is performed in the MCT1 gene. In the most preferred variant, for training in the development of anaerobic endurance, detection includes a genetic variant

[0058] In the preferred variant, for training in exercise energy, detection of polymorphisms is performed in genes selected from the group comprising ACTN3, ACE and / or HIFla. In the more preferred variant, detection is performed in each gene listed, meaning that for training in exercise energetics, detection of polymorphisms is performed in genes selected from the group consisting of ACTN3, ACE and HIFla. In the most preferred variant, for training in exercise energetics, detection includes genetic variants consisting of the following group:

[0059] In the preferred variant, for training in information processing under stress-inducing conditions, detection of polymorphisms is performed in the COMT gene. In the most preferred variant, for training in the development of anaerobic endurance, detection includes a genetic variant

[0060] The method for individualised management of a subject dietary supplementation is divided into steps.

[0061] In a first step of a method for management of dietary supplementation of a subject according to the invention, a genetic sample taken from the subject is evaluated for the presence of polymorphisms in genes selected from the group comprising UCP2, PPARA, and / or AMPD1 to obtain a genetic profile. Thus, a genetic profile of the subject is obtained.

[0062] In a preferred variant, detection is performed in each listed gene. This means that the genetic profile obtained by the method for training management according to the invention consists of the listed genes, detection may also be performed in one specifically identified gene or any combination of the listed genes. This means the present disclosure also discloses such variants where detection is performed in any combination of the listed genes.

[0063] In the second step, an analysis of a genetic profile is performed to identify genetic variants specifically responsible for regulating ATP and reactive oxygen species levels in the subject.

[0064] In the third step of the method according to the invention, the dietary supplementation of a subject for mitochondria-directed antioxidants and D-ribose, xylitol and / or other sugars is determined based on the genetic profile obtained

[0065] Preferably, mathematical analysis, in particular providing for machine learning, is used to carry out the method and object.

[0066] For example, the method for management of dietary supplementation according to the invention allows for determine that a subject should supplement sugars or antioxidants prior to intense exercise. This will allow the subject to improve his / her ability to sports development in the respective sports discipline.

[0067] A method for prediction of the injury susceptibility of the subject is divided into steps.

[0068] In the first step of a method for prediction of the injury susceptibility of a subject according to the invention, a genetic sample taken from the subject is evaluated for the presence of polymorphisms in genes selected from the group comprising COL5A1 and / or MMP3 to obtain a genetic profile. Thus, the genetic profile of the subject is obtained.

[0069] In a preferred variant, detection is performed in each listed gene. This means the genetic profile obtained by the method for injury susceptibility prediction according to the invention consists of the listed genes. Detection can also be performed in one specifically identified gene.

[0070] In the second step, an analysis of a genetic profile is performed to identify genetic variants specifically responsible for susceptibility to soft tissue injuries.

[0071] In the third step of the method according to the invention, it is determined whether a subject is susceptible to soft tissue injuries based on the genetic profile obtained

[0072] Preferably, mathematical analysis, in particular providing machine learning, is used to carry out the method and object

[0073] The method for injury susceptibility prediction according to the invention thus allows for determining whether a subject is susceptible and to what extent to non-contact soft tissue injuries. It also allows for adjusting sports development training and preventing injuries in the future.

[0074] The list of genes (their respective combination) and polymorphisms was compiled based on the experience of the inventors and partial information contained in the state of the art. Said polymorphisms are responsible for the determination of related traits and influencing the sports development of a subject in sports disciplines. However, such a set of genes, providing for the aforementioned set of genetic variants, has not yet been researched for its predictive capacity for sports development. Even more so, methods based on mathematical analysis, in particular machine learning methods, have not been used to identify genetic predispositions.

[0075] As yet known genetic tests in sport are mainly used to indicate simple relationships between a specific polymorphism and general conditioning for professional sporting activities. Although single gene polymorphisms have been identified in the state of the art as factors influencing the physical traits development in athletes (e.g. ACTN3 or ACE), single polymorphisms are not able to act as reliable predictors. This is because of the complexity of traits determination of the sports development of subjects at the highest level. It is therefore necessary to develop, polygenic profiles that consider the interaction of the products of particular genes with each other at the cellular level.

[0076] The model used in the present invention presents a complex approach that allows for considering interactions between polymorphisms, to distinguish traits suitable for a specific role in a team in a given sport and to predict the expected progress of subjects, i.e. their sports development. This allows for the creation of decision rules to determine a subject potential for sports development and to manage the training process.

[0077] The analysis methods used in the present invention are based on mathematical analysis with machine learning. These methods allow for intuitive modelling of the relationships between the many considered traits but do not require a prior ("upfront") imposition of a relationship structure. Thus, genetic determinants can be easily linked to training achievements, body measurements or psychological test results. Since the analysis model used in the present invention is not a rigid model, a sufficiently large sample size allows for the use of measurements collected diversely.

[0078] Using unsupervised machine learning methods, called segmentation or clustering, the present invention identified previously undescribed relationships between theoccurrence of polymorphisms in selected genes and the results of specific conditions, such as increased endurance or running speed. Combined with training results, this ensued in a method for analysis of an athlete's progress and his / her sports development

[0079] The method according to the present invention allows for identifying the predisposition of subjects, allowing to focus on the elements for which the subject is conditioned. This allows for maximising the sporting potential of the subject.

[0080] The analysis methods used in the present invention are based on rough set theory. This theory allows sets to be defined using their lower and upper rough calculation rather than strictly defined boundaries. This approach is useful for finding hidden relationships between data.

[0081] The basic term of rough sets is the ordered fourfoldexpressing an information system where U indicates a finite set of objects (e.g. subjects), Q indicates a finite set of attributes (e.g. genetic tests), V is set of attribute values from set of and finally f is an information function such that / for each u

[0082] An indistinguishability relation is defined between the rough sets. It is to be generated by objects to set U. This helps in the automatic extraction of knowledge and thus in the generation of decision rules from the data. In a formal method, this relation is expressed as follows: Letbe an information system and let A∈B.

[0083] The indistinguishability relation NR on set of objects U generated by set of attributes B is defined asare the objects belonging to the product of the Cartesian set of universe, A∈B are each attribute set B, is the information function for the pair: object x and attribute α .

[0084] Subject pairs of objects are in a A7 / ?,(B) relationship with each other when they have the same values for all attributes in set B. For example, set B may be the potential of a subject for sports development. Then, subjects with the same potential but different other parameters are in an indistinguishability relationship with each other. The use of fuzzy sets and indistinguishability rules facilitates the selection of functional decision rules and synergies between attributes of different types.

[0085] In order to make certain decision rules effective, they are selected from the reducts, i.e. the minimum set describing the objects of interest. From a formal point of view, it is said that attribute is redundant if

[0086] Otherwise namely when attribute a is essential. Then setB ∈ A is called a reduct A if and only if The use of reducts allowsa precise description of the relationships between objects and the selection of minimum decision rules reducing costs.

[0087] The methods for the analysis of the sports development of a subject using genetic testing and machine learning algorithms developed in the present invention have a higher sensitivity compared to previously used methods. The method according to the invention allows the precise identification of the sports development potential of subjects and the appropriate selection of training processes.

[0088] The same relationships and mathematical analyses disclosed above apply to the other methods according to the invention.

[0089] The ACTN3 gene is the gene encoding the protein a-actinin-3. This protein, found only in type II (fast contracting) muscle fibres, acts as a stabiliser of actin filaments therein. The ACTN3 gene is responsible for fast muscle contraction and protection against muscle damage, such as resistance to muscle damage from eccentric training. The marker is the R577X mutation, which results in an earlier occurrence of the so- called STOP codon and thus a lack of a-actinin-3 production.

[0090] The ACE gene is the gene encoding the angiotensin-converting enzyme protein. The ACE gene broadly determines athletic predisposition; in particular, it is a genetic marker accounting for predisposition to long-distance sports, to greater gains in muscle strength as a result of endurance training and to better oxygen supply / utilisation under conditions of oxygen deprivation. The marker is the I / D polymorphism. The I / D polymorphism results from the presence of a specific mutation involving the presence (I, insertion) or absence (D, deletion) of the so-called Alu sequence in intron 16 of the ACE gene.

[0091] The HIFla gene encodes hypoxia-inducible factor alpha 1. The HIFla gene has a strong influence on the formation of type IIx muscle fibres.

[0092] The MCT1 gene encodes monocarboxylate transporter 1. The MCT1 gene is responsible for the transport of lactic acid at the cellular level. Its respective variant (AA vs TA / TT) allows for faster elimination of this metabolite from the blood after anaerobic exercise (e.g. sprint or Wingate test).

[0093] The UCP2 gene encodes mitochondrial uncoupling protein 2. The main function of UCP2 is to control mitochondrial-derived reactive oxygen species. The UCP2 gene is expressed in many tissues, with the highest expression in skeletal muscles.

[0094] The PPARA gene encodes alpha receptors activated by peroxisome proliferators. It is responsible for carbohydrate, fat and protein metabolism.

[0095] The AMPD1 gene contains instructions for the production of an enzyme called adenosine monophosphate (AMP) deaminase. This enzyme is found in muscles used for movement (skeletal muscles), where it plays a role in energy production.

[0096] The COMT gene contains instructions for the production of an enzyme called catechol-O-methyltransferase. This enzyme facilitates the control of levels of hormones such as dopamine, epinephrine and norepinephrine.

[0097] The MMP3 gene encodes matrix metalloproteinase-3. This enzyme is responsible for the degradation of various types of collagen, proteoglycans, fibronectin, laminin and elastin. MMP3 can also activate other genes in the MMP family, making it a key gene in connective tissue restoration.

[0098] The COL5A1 gene encodes alpha- l(V)-collagen found mainly in ligaments and tendons. The COL5A1 gene is responsible for the mechanical properties of tendons and influences the predisposition to musculoskeletal injury.

[0099] A subject is understood to be any animal, preferably a mammal, e.g. human, dog, horse, etc. More preferably, a subject is a human being.

[0100] A genetic sample is understood to be any material (e.g. fluid) taken from a subject that carries genetic information. Examples of such materials are e.g. liquid materials such as blood or saliva or solid materials such as hair or skin.

[0101] Sports development is understood as the performance of sporting exercises aimed at preparing a subject to participate and compete in sporting events (e.g. tournaments, competitions, etc.). In particular, the sports development of a subject identified at an early step of development as a talent in a given sport means that, through sporting training, the subject passes through successive steps of development to become a better athlete (e.g. participates in sporting competitions at championship level, belongs to the elite of athletes in a given field in a given geographical area, etc.).

[0102] Sports disciplines are defined as sports disciplines in which subjects have the opportunity to compete. These sports can be both team and individual sports disciplines, can be summer, winter and year-round sports, can be Olympic and nonOlympic sports disciplines. In particular, the present invention relates to sports such as volleyball, football, basketball, handball, American football, rugby, hockey, cricket, tennis, and golf. The list is non-limiting in nature.

[0103] Physical-mental training is understood as training involving both the physical and mental qualities of a subject. Physical training includes training in power, aerobic endurance, anaerobic endurance, eccentric muscle work and exercise energy. Mental qualities include training in the ability to process information under stressful conditions.

[0104] Training the ability to process information under stress-inducing conditions is understood as training in connection with a potential disruption of informationprocessing and concluding stress. The result is a recommendation either for cyclic repetition of elements of the technique of the respective sport under stress-inducing conditions - up to the development of reflex action, or for the development of creativity in the selection of elements of the technique of the respective sport under stress-inducing conditions.Examples

[0105] Example 1: A general example embodiment of a method for the determination of a genetic physical predisposition of a subject for sports development in sports disciplines.

[0106] The method according to the invention includes the step of evaluation of a genetic sample of a subject for the presence of polymorphisms traits associated with sports development in sports disciplines in order to obtain a polygenic profile. Detection of polymorphisms is performed in genes selected from a group comprising ACTN3, ACE, HIFla, MCT1, UCP2, PPARA, AMPD1, COMT, MMP3 and / or COL5A1.

[0107] The evaluation is made on the basis of a sample of genetic material collected from the subject, such as a swab from the subject mouth. Subsequently, DNA is isolated according to the protocol provided by the manufacturer of the commercial DNA isolation kit. Amplification of polymorphic regions in the subject is performed by PCR. After this, Sanger sequencing is performed. These methods are well known in the field.

[0108] The next step concerns polygenic profile analysis, where the following genetic variants are identified:

[0109] Based on the polygenic profile obtained, the predisposition of the test subject to play a specific sports discipline is determined. For this purpose, the mathematical analysis model disclosed above based on rough set theory using machine learning methods is used.

[0110] The results obtained allow to determine whether a subject shows a predisposition for specific sports disciplines, i.e. whether his / her genetic profile fits the genetic profile of elite athletes in his / her discipline as described below.

[0111] From the experimental data obtained for representative sports disciplines (volleyball, basketball, football), it is apparent that the method according to the invention applies to sports which are characterised by requirements for competition and competitiveness. Examples of such sports disciplines are listed above.

[0112] Example 2: Method for determination of a genetic physical predisposition of a subject for sports development in volleyball

[0113] According to Example 1, genetic material was collected from subjects and genetic analyses were performed by determining the polygenic profiles of the subjects. The study group consisted of 29 professional volleyball World Champions from 1974, 2014 and 2018. The control group consisted of 32 youth volleyball players, including: 10 youngsters, 12 cadets and 10 juniors.

[0114] The results obtained were part of the data set #1 of volleyball players. A detailed analysis of the distribution of the volleyball profile in data set #1 is presented in the table below:

[0115] Then, to verify the effectiveness of the method according to the invention, i.e. the effectiveness of the prediction, the obtained profile was tested on an independent group of volleyball players. This group included: 10 most outstanding players of the SMS Spala volleyball club (championship group 2) and 26 youth players, participants of the 2013 Olympic Hopes Tournament (youth group 2). The results obtained constituteddata set #2. A detailed analysis of the volleyball profile distribution in data set #2 is presented in the table below:

[0116] As can be seen from the above analysis, the profile obtained by the method according to the invention characterised the master group and distinguished it significantly from the youth group (for data set #1: p=0.00039, Fisher's exact test; for data set #2: p=0.0262, Fisher's exact test).

[0117] At the same time, an analysis of the frequency of the profile obtained by the method according to the invention in the championship group and championship group "2" showed that the profile does not differentiate between these groups (p=0.4798, Fisher's exact test), which further confirms the effectiveness of its use as a predictor of success in volleyball.

[0118] Details of the analysis are shown in the table below:

[0119] Conclusions

[0120] Among the Polish national volleyball team of the best volleyball players trained over the last 50 years, there is a clear overrepresentation of specific variants of the studied genes occurring with the polymorphisms defined in the present invention. This indicates, a significant contribution of the studied genes in shaping physical traits relevant to professional volleyball at the highest level. In particular, in the case of retina, the polygenic profile should be developed based on detection of polymorphisms in the following genes: ACTN3, ACE, HIFla, MCT1, UCP2, PPARA, AMPD1, COMT, MMP3 and COL5A1. The polygenic profile obtained allows to conclude thatthe best professional volleyball players are characterised by a predisposition for both the development of high muscular power and athletic body performance.

[0121] Example 3: Method for determination of the genetic physical predisposition of a subject for sports development in football

[0122] According to Example 1, genetic material was collected from subjects and genetic analyses were performed by determination of the polygenic profiles of the subjects. The study group consisted of 13 professional footballers, including 5 Polish national football players. The control group consisted of 25 youth group players, including 23 players from the Legia Warszawa football academy and 2 players playing for a Polish third-class club.

[0123] The results obtained were analysed given the frequency of the profile in both study groups. Detailed data are presented in the table below:

[0124] As can be seen from the above analysis, the profile obtained by the method according to the invention characterised the professional group and distinguished it significantly from the youth group (p=0.0009, Fisher's exact test).

[0125] Then, in order to verify the effectiveness of the method according to the invention, i.e. the effectiveness of prediction, the obtained profile was tested. The test of the effectiveness of the prediction using the obtained profile consisted of analysing the market value of the analysed youth players between 2012 and 2021. All (100%) of the players fitting the profile achieved a valuation of EUR 200,000 or more. Among the players not fitting the profile, sixteen per cent (16%) of the players reached or exceeded the reference value of EUR 200,000 (valuation of footballers according to transfermarkt.de).

[0126] This analysis was performed not only at the level of individual players but also of entire groups. A detailed analysis of the groups of young footballers fitting and not fitting the profile is presented in the table below. Statistical analysis was performed using one-way analysis of variance (ANOVA).

[0127] Conclusions

[0128] Among professional football players, there is a clear overrepresentation of specific variants of the studied genes occurring with the polymorphisms defined in the present invention. This indicates that the test genes are significantly involved in shaping physical traits relevant to professional football at the highest level. Specifically, for football, the polygenic profile should be developed based on the detection of polymorphisms in the following genes: ACTN3, ACE, HIFla, MCT1, UCP2, PPARA, AMPD1, COMT, MMP3 and COL5A1. The resulting polygenic profile allows to conclude that the best professional football players are characterised by a predisposition for both the development of high muscular power and body performance. The analysis of the effectiveness of the prediction also based on the market value of the players proves that the polygenic profile of a professional footballer determined by the method according to the invention is an effective tool for predicting the sport development of future professional footballers.

[0129] Example 4: Method for determination of the genetic physical predisposition of a subject for sports development in basketball

[0130] According to Example 1, genetic material was collected from subjects and genetic analyses were performed by determining the polygenic profiles of the subjects. The study group consisted of 11 Polish basketball representatives for the Tokyo 2020 Olympic Games. The control group consisted of 55 non-basketball youth group players: 32 volleyball players and 23 football players.

[0131] The results obtained were analysed given the frequency of the profile in both study groups. Detailed data are presented in the table below:

[0132] As can be seen from the above analysis, the profile obtained by the method according to the invention characterised the professional group and distinguished it significantly from the youth group. Statistical analysis showed significant differences in the incidence of the profile in the group of professional basketball players and the youth group, both using the Chi-square test (p=0.002372) and Fisher's exact test (p=0.012), which indicates that the profile obtained using the method according to the invention effectively differentiates Olympic-level basketball players from young players starting their sports careers in other disciplines.

[0133] Conclusions

[0134] Among professional basketball players, there is a clear overrepresentation of specific variants of the studied genes occurring with the polymorphisms defined in the present invention. This indicates that the test genes are significantly involved in shaping physical traits relevant to professional basketball at the highest level. Specifically, for basketball, the polygenic profile should be developed based on the detection of polymorphisms in the following genes: ACTN3, ACE, HIFla, MCT1, UCP2, PPARA, AMPD1, COMT, MMP3 and COL5A1. The polygenic profile obtained allows to conclude that the best professional basketball players are characterised by a predisposition for both the development of high muscular power and athletic performance.

[0135] Example 5: General example of the implementation of a method for individualised sports training management of a subject

[0136] The method for individualised training management according to the invention includes the step of evaluation of a genetic sample of a subject for the presence of polymorphisms. Detection of polymorphisms is performed in genes selected from a group comprising ACTN3, ACE, HIFla, MCT1, UCP2, PPARA, AMPD1, COMT, MMP3 and / or COL5A1.

[0137] The analysis of a genetic profile identifies genetic variants such as for the profile analysis in the method for determination of the genetic predisposition of the subject for sports development in sports disciplines (according to Example 1).

[0138] The evaluation is conducted based on a sample of genetic material taken from the subject following the requirements described in Example 1.

[0139] Based on the genetic profile obtained and genetic variants, physical and mental traits (physical-mental characteristics) are identified that should be trained by the subject to improve sporting ability (performance in a given sport). For this purpose,the mathematical analysis model disclosed above based on rough set theory using machine learning methods is used. The physical-mental traits that are identified and intended to determine training thanks to the genetic profile obtained by the method according to the invention are power, aerobic endurance, anaerobic endurance, muscle eccentric work, exercise energetics, ability to process information under stressinducing conditions.

[0140] With this data, a training programme is determined for the subject providing for the need to develop the listed physical traits based on the genetic profile obtained.

[0141] Example 6: Method for individualised training management according to the invention

[0142] Following Example 5, genetic material was collected from the subjects and genetic analyses were performed to determine the genetic profiles of the subjects.

[0143] The analyses performed allowed to identify relationships of the type: gene vs. natural ability to train a specific physical-mental trait. The following results were obtained ("+" indicates that a gene is important in individualising the training of a particular physical-mental trait):

[0144] Based on the profiles obtained, subjects with a natural predisposition to develop the physical and mental traits mentioned herein were identified and training optimisation was performed for these subjects.

[0145] The study group was football players from the football academy of the club Rakdw Czestochowa. Twenty-four young footballers aged 13 were qualified for the study.

[0146] The study group was genetically profiled and, based on their profiles, their training was optimised for the listed physical and mental characteristics.

[0147] The effectiveness of the individualised method for training management was examined based on parameters of motor characteristics including maximal oxygenconsumption (max VO2), development of muscular explosive power (5 m sprint), capillary lactate levels and heart rate after an intermittent 30-15 performance test

[0148] The test group was trained according to the method according to the invention for 8 weeks using genetic profiling and according to the standard method (i.e. without optimised training based on genetic profiling). All monitored parameters were measured before the first training cycle (initial measurement), after the first training cycle (standard training without genetic profiling) and after the second training cycle (individualised training with genetic profiling according to the invention).

[0149] Results

[0150] Statistical analysis of the data obtained disclosed significant improvements in all parameters measured:

[0151] An increase in maximum aerobic velocity (reflecting the max VO2 parameter) of 0.26 m / s (from 4.68 m / s to 4.94 m / s).

[0152] Increase in maximum terminal speed (30-15 test, Vmax) by 1.2 km / h (from 20.2 km / h to 21.3 km / h).

[0153] Reduction in time to cover a distance of 5 m (explosive muscle power) by 39 ms (from 1124 ms to 1085 ms).

[0154] Reduction in acidity after the 30-15 IFT test by 24% (from 13.3 mmol / 1 to 10.1 mmol / 1).

[0155] The individualised training cycle led to significant improvements in all key areas of the young athletes' development. In contrast, heart rate did not change after the second training cycle compared to the first training cycle. This indicates that the training load remained unchanged, despite a significant increase in the development of the athletes after the implementation of the method according to the invention.

[0156] Finally, the data obtained by the method according to the invention were compared with the historical data obtained by standard training. Unexpectedly, it turned out that the measured parameters were at least twice as preferred for training optimised according to the method disclosed herein (i.e. with genetic profiling).

[0157] Hence, based on the results obtained and genetic profiling, training is planned and optimised according to the following scheme:

[0158] Example 7: Example embodiment of a method for individualised management of dietary supplementation of a subject

[0159] The method for individualised management of dietary supplementation according to the invention includes a step of evaluation of a genetic sample of a subject for polymorphisms. Detection of polymorphisms is performed in genes selected from a group comprising UCP2, PPARA, and / or AMPD1.

[0160] The analysis of a genetic profile identifies genetic variants such as for the profile analysis in the method for determination of the genetic predisposition of a subject for sports development in sports disciplines (according to Example 1).

[0161] The evaluation is made based on a sample of genetic material taken from the subject following the requirements described in Example 1.

[0162] Based on the resulting genetic profile and genetic variants, the genetic variants responsible for the regulation of ATP and reactive oxygen species levels in the subject are identified.

[0163] Specifically, dietary supplementation is being pursued for impaired AMP breakdown reactions to IMP and urea to replenish ATP levels during anaerobic exercise. In this case, the subject is analysed for polymorphism in the AMPD1 gene (rs 17602729). If a subject has the mutation, supplementation with sugars, particularly d-ribose or xylitol, is recommended. In particular, such supplementation is recommended before intense exercise.

[0164] Dietary supplementation is also performed because of potentially increased levels of oxygen free radicals in the mitochondria due to increased ATP production. In this case, the subject is analysed for polymorphism in the UCP2 and / or PPARA gene. If a subject has a mutation, supplementation with antioxidants, particularly those that accumulate in the mitochondria (e.g. MitoQ and / or SkQl), is recommended. In particular, such supplementation is recommended before intensive physical exercise

[0165] This determines a subject supplementation programme based on the genetic profile obtained and improves motor parameters given power and aerobic endurance and / or anaerobic endurance.

[0166] Example 8: Example embodiment of a method for prediction of susceptibility to noncontact soft tissue injuries ("contusions") of a subject

[0167] The method for prediction of injury susceptibility according to the invention includes the step of evaluation of a genetic sample of a subject for the presence of polymorphisms. Detection of polymorphisms is performed in genes selected from the group comprising COL5A1 and / or MMP3.

[0168] The analysis of a genetic profile identifies genetic variants such as for the profile analysis in the method for determination of the genetic predisposition of a subject for sports development in sports disciplines (according to Example 1).

[0169] The evaluation is made based on a sample of genetic material taken from the subject following the requirements described in Example 1.

[0170] Based on the genetic profile and genetic variants obtained, the genetic variants responsible for susceptibility to soft tissue injuries are identified.

[0171] The final step of the method evaluates whether the subject is susceptible to soft tissue injuries.

[0172] Specifically, the implementation of the modality provides an evaluation result of whether a subject is susceptible to non-contact soft tissue injuries. The outcome of the evaluation is a determination of whether the risk is low, high or very high. Polymorphicity analysis in the COL5A1 gene (rs 12722) and / or MMP3 (rs679620) is used for the evaluation.

[0173] Eight football players with recurrent non-contact soft tissue injuries (injury-prone players) and seven football players with no documented recurrent non-contact soft tissue injuries (non-injury-prone players) were included in the study to confirm the effectiveness of the method according to the invention.

[0174] The results obtained were analysed given the frequency of the genetic profile in both study groups. The results obtained are presented in the table:

[0175] The injury-prone group was analysed in detail concerning the type of injury and the age at which the injury occurred. This analysis indicates that the genetic profile obtained by the method according to the invention is a good predictor of injury occurrence and can reduce the number of injuries if appropriate training and supplementation prophylaxis is introduced in subjects. The details are shown in the table ("+" indicates an athlete with a non-contact soft tissue injuries susceptibility profile according to the invention):Industrial Applicability

[0176] The methods according to the invention can be used to generate genetic profiles and identify sports talents at the earliest possible step of their development, manage their sports development and develop training processes. The methods according to the invention can also be used to establish a polygenic profile template used for a first broad selection among candidates for professional athletes, e.g. volleyball players, football players, basketball players, etc.

[0177] The methods according to the invention are also used to develop the individualised training of the subject and dietary supplementation, which has a positive effect on his sports development given sporting-mental characteristics. Thanks to the present invention, it is also possible to prevent injuries to the subject such as tendon ruptures and tendinopathies, ligament ruptures or muscle ruptures.

[0178] Furthermore, it is to be understood that the applications of the invention listed and described above are only given by way of example. All example embodiments and variants thereof are given herein only as non-limiting indications of the invention and may in no way limit the scope of protection, which is defined by the claims of the patent It should be understood that any technical solution used in the methods, nucleic acid molecules and / or kits according to the invention can be carried out by means of equivalent technologies without exceeding the scope of protection.

[0179] In addition, the use of the singular form when referring to individual elements of the invention also includes their plural form and vice versa, unless the context indicates otherwise.

Claims

Claims

1. A method for determination of the genetic predisposition of a subject for sports development in sports disciplines, the method including the following steps: a) evaluation of a genetic sample of the subject for the presence of polymorphisms in genes determining the formation of physical traits associated with the subject sports development in sports disciplines to obtain a polygenic profile, wherein analysis of polymorphisms is performed in genes selected from a group comprising ACTN3, ACE, HIFla, MCT1, UCP2, PPARA, AMPD1, COMT, MMP3 and / or C0L5A1, b) analysis of polygenic profile to identify genetic variants responsible for predisposition to sports disciplines, c) determination of the subject predisposition to practice a sports discipline based on the polygenic profile obtained, wherein the analysis of genetic profile is performed using rough set analysis based on a machine learning algorithm, wherein the information system S is defined by the formulawhere U indicates set of subjects, Q indicates set of values obtained from the genetic tests, V indicates set of attribute values from set of and where f is aninformation function such that for each uwherein based on the values of set U, the indistinguishability relation is generated, defined by the formulawhereare the objects belonging to the product of the Cartesian set of universe, A∈B are each attribute of set B, is the information function for the pair: object x andattribute α, where specific pairs of objects are in a relation with each other NRS(B ) when they have the same values for all attributes from set B, wherein the resulting polygenic profile includes the following genetic variants:

2. A method for individualised management of a subject sports training including the following steps: a) evaluation of a genetic sample of a subject for the presence of polymorphisms in genes selected from a group comprising ACTN3, ACE, HIFla, MCT1, UCP2, PPARA, AMPD1, COMT, MMP3 and / or COL5A1 to obtain a genetic profile, b) analysis of a genetic profile to identify genetic variants responsible for the development of physical-mental traits, the traits identified including power, aerobic endurance, anaerobic endurance, muscle eccentric work, exercise energy, ability to process information under stress-inducing conditions, c) determination of a training programme for the subject providing for the need to develop the listed physical traits based on the genetic profile obtained.

3. The method according to claim 2, wherein the resulting genetic profile includes the following genetic variants:

4. The method according to claim 2 or 3, wherein for training in the power development, detection of polymorphisms is performed in genes selected from a group comprising ACTN3, ACE, HIFla, UCP2, and / or PPARA.

5. The method according to claim 2 or 3, wherein for training in the development of aerobic endurance, detection of polymorphisms is performed in genes selected from the group comprising ACE, HIFla, and / or PPARA.

6. The method according to claim 2 or 3, wherein for training in the development of anaerobic endurance, detection of polymorphisms is performed in the MCT1 gene.

7. The method according to claim 2 or 3, wherein for training in eccentric muscle work, detection of polymorphisms is performed in genes selected from the group comprising ACTN3 and / or ACE.

8. The method according to claim 2 or 3, wherein for training in exercise energy, detection of polymorphisms is performed in genes selected from the group comprising ACTN3, ACE and / or HIFla.

9. The method according to claim 2 or 3, wherein for training in information processing under stress-inducing conditions, detection of polymorphisms is performed in the gene COMT.

10. A method for individualised management of a subject dietary supplementation including the following steps: a) evaluation of a genetic sample of a subject for the presence of polymorphisms in genes selected from a group comprising UCP2, PPARA, and / or AMPD1 to obtain a genetic profile, b) analysis of a genetic profile to identify genetic variants responsible for regulating ATP and reactive oxygen species levels in a subject, c) determination of dietary supplementation of a subject for mitochondria-directed antioxidants and D-ribose, xylitol and / or other sugars based on the genetic profile obtained.

11. A method for injury susceptibility prediction of a subject including the following steps: a) evaluation of a genetic sample of a subject for the presence of polymorphisms in genes selected from a group comprising COL5A1 and / or MMP3 to obtain a genetic profile, b) analysis of a genetic profile to identify genetic variants responsible for susceptibility to soft tissue injuries, c) determination of whether a subject is susceptible to soft tissue injuries.

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