Muscle characteristic analysis method

Abstract

To provide a method for determining skin characteristics with a higher degree of reliability from the relationship between previously unknown SNPs and skin characteristics, a computer for determining skin characteristics, and a program for controlling the computer. The present invention provides a method for determining skin characteristics, which includes the steps of detecting at least one SNP selected from a group consisting of specific SNPs, and determining the skin characteristics based on the detected SNP.

Description

Technical Field

[0001] The present invention relates to a method for determining human skin characteristics based on genetic factors by SNP analysis, a computer for determining skin characteristics, and a program for controlling the computer. Based on the determined skin characteristics, it becomes possible to provide beauty guidance services and select cosmetics and supplements.

Background Art

[0002] Skin characteristics vary widely from person to person. In order to provide cosmetics suitable for each individual's skin characteristics, individual counseling has mainly been carried out in the past. The counseling has been based on the questionnaire results by the customer's self-diagnosis and the objective information of the skin, such as the texture measured by equipment, skin barrier function, moisture content, elasticity, viscosity, etc.

[0003] However, the customer's self-diagnosis is only a subjective judgment and does not accurately reflect the customer's skin characteristics. In addition, the objective information measured by equipment only quantifies the state at the time of inspection for the skin condition that can change daily, and it has been difficult to predict possible future skin troubles.

[0004] If it is possible to predict possible future skin troubles in advance, preventive measures can be taken, which is very useful.

[0005] In recent years, skin tests based on SNP analysis of genes have been proposed. In particular, regarding genes encoding proteins directly involved in skin quality, the relationship between SNPs and skin quality has been studied (Patent Documents 1 to 4). As a result, methods for predicting skin characteristics and skin problems have been provided based on SNP analysis results. In these studies, SNPs have been investigated for genes that have been shown to be directly involved in skin quality, such as wrinkles and spots. Examples of such target genes include MC1R, MMP1, SOD2, GPX1, ASIP, etc. On the other hand, since genes that affect skin characteristics of the skin are diverse, it is necessary to investigate the relationship between SNPs and skin characteristics in more genes.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Non-Patent Documents

[0007]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0008] An object of the present invention is to investigate the relationship between SNPs that have not been known so far and skin characteristics, and to develop a method for determining skin characteristics with higher reliability. [Means for Solving the Problems]

[0009] The inventors of the present invention attempted statistical analysis of the relationship with skin characteristics by targeting SNPs not only in proteins whose relationship with skin characteristics has been known so far but also in a wider range of proteins in 200 subjects. As a result, SNPs related to skin characteristics, particularly wrinkles, skin color, and skin function, were identified, leading to the present invention.

[0010] Therefore, the present invention is the following invention: The step of detecting at least one SNP selected from the group consisting of rs1030868, rs1050565, rs10515552, rs10741657, rs11057830, rs1107946, rs1256062, rs12785878, rs12931267, rs1501299, rs17822931, rs1799750, rs1800414, rs1800629, rs2046571, rs2241145, rs2246416, rs2285053, rs2287074, rs2987983, rs3760776, rs3829251, rs6058017, rs74653330, rs7501331, rs8326, rs833061, rs11234027, rs16891982, rs17577, rs1799724, rs1800012, rs2010963, rs2108622, rs2232228, rs3785079, rs7799039, rs10882272, rs1485766, rs1540771, rs7201, rs964184, rs1993116, rs2060793, rs2282679, rs12272004, rs2227564, rs2298585, rs4065, rs4880, rs492602, rs12051272, rs1126643, rs2234693, rs3865188, rs11568737, rs1801133, rs2228479, rs41281112, rs1061622, rs8110862, rs9340799, rs12377462, rs1667255, rs12913832, and rs4654748 The step of determining skin characteristics based on the detected SNP relates to a method for determining skin characteristics, including the above steps.

[0011] In yet another aspect, the present invention is a computer for determining skin characteristics, comprising the following: Information regarding at least one SNP selected from the group consisting of rs1030868, rs1050565, rs10515552, rs10741657, rs11057830, rs1107946, rs1256062, rs12785878, rs12931267, rs1501299, rs17822931, rs1799750, rs1800414, rs1800629, rs2046571, rs2241145, rs2246416, rs2285053, rs2287074, rs2987983, rs3760776, rs3829251, rs6058017, rs74653330, rs7501331, rs8326, rs833061, rs11234027, rs16891982, rs17577, rs1799724, rs1800012, rs2010963, rs2108622, rs2232228, rs3785079, rs7799039, rs10882272, rs1485766, rs1540771, rs7201, rs964184, rs1993116, rs2060793, rs2282679, rs12272004, rs2227564, rs2298585, rs4065, rs4880, rs492602, rs12051272, rs1126643, rs2234693, rs3865188, rs11568737, rs1801133, rs2228479, rs41281112, rs1061622, rs8110862, rs9340799, rs12377462, rs1667255, rs12913832, and rs4654748, and information on skin characteristics related to the SNP, stored in a storage unit An input unit for inputting the DNA information of a user A detection unit for detecting the presence of the stored SNP in the input DNA information An output unit for outputting information on skin characteristics related to the detected SNP Relating to a computer including the above. In a further aspect of the present invention, it also relates to a method for controlling such a computer and / or a control program, and further to a storage medium storing such a control program.

[0012] Furthermore, the present invention also relates to a method for determining skin characteristics, and a method for providing a cosmetic, a supplement, and / or a beauty method based on the skin characteristics determined by a computer that determines the skin characteristics.

Advantages of the Invention

[0013] According to the present invention, it becomes possible to determine skin characteristics, and it becomes possible to provide a cosmetic, a supplement, and / or a beauty method based on the determined skin characteristics.

Brief Description of the Drawings

[0014]

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DETAILED DESCRIPTION OF THE INVENTION

[0015] The present invention relates to a method for determining skin properties, including a step of detecting SNPs associated with skin properties, and a step of determining skin properties based on the detected SNPs. Here, the SNPs associated with skin properties include the following: At least one SNP selected from the group consisting of rs1030868, rs1050565, rs10515552, rs10741657, rs11057830, rs1107946, rs1256062, rs12785878, rs12931267, rs1501299, rs17822931, rs1799750, rs1800414, rs1800629, rs2046571, rs2241145, rs2246416, rs2285053, rs2287074, rs2987983, rs3760776, rs3829251, rs6058017, rs74653330, rs7501331, rs8326, rs833061, rs11234027, rs16891982, rs17577, rs1799724, rs1800012, rs2010963, rs2108622, rs2232228, rs3785079, rs7799039, rs10882272, rs1485766, rs1540771, rs7201, rs964184, rs1993116, rs2060793, rs2282679, rs12272004, rs2227564, rs2298585, rs4065, rs4880, rs492602, rs12051272, rs1126643, rs2234693, rs3865188, rs11568737, rs1801133, rs2228479, rs41281112, rs1061622, rs8110862, rs9340799, rs12377462, rs1667255, rs12913832, and rs4654748 is used.

[0016] In the present invention, SNPs are represented by rs numbers (Reference SNP ID numbers). For detailed information (positions on chromosomes and mutations) of SNPs corresponding to each rs number, they are managed by the National Center for Biotechnology Information (NCBI) in the United States and can be referred to on the NCBI homepage (http: / / www.ncbi.nlm.nih.gov / ).

[0017] The detection of SNPs may be performed by any known method. As an example, nucleic acids of a subject are purified from a biological sample of the subject, such as saliva, blood, mucosa, tissue pieces, hair, etc., based on a conventional method, and SNPs are detected in the purified nucleic acids. Therefore, the method for determining skin characteristics of the present invention may further include a sample preparation step and a nucleic acid purification step. The nucleic acid may be DNA or RNA. In the case of RNA, it is preferable to perform reverse transcription after purification to prepare DNA. In the SNP detection step, any method can be used as long as it enables the detection of SNPs in the purified nucleic acid. It is also possible to detect SNPs by determining the sequence around the position of the target SNP, or by using a method based on the PCR method, a method using a DNA probe, or a method using mass spectrometry. Examples of the method based on the PCR method include the SNP typing method, the TaqMan PCR method, the single-base extension method, the Pyrosequencing method, and the Exonuclease Cycling Assay method. Examples of the method using a DNA probe include the Invader method (Genome-wide polymorphism analysis (SNP), Nippon Yakurigaku Zasshi, 125, 148-152, 2005). SNPs may be accompanied by another SNP in linkage disequilibrium. By detecting the SNP in linkage disequilibrium with the target SNP, the target SNP can be detected. Therefore, in the present invention, the detection of SNPs is not limited to directly detecting the target SNP, and detecting the target SNP by detecting the SNP in linkage disequilibrium is also included.

[0018] In addition, the presence of SNPs can also be detected based on the nucleotide sequence of an individual whose sequence has already been determined. In this case, the presence of SNPs can be detected by examining the sequence at the position where SNPs are present within the data of the already determined nucleotide sequence. Therefore, in this case, the detection of SNPs may be performed by inputting the nucleotide sequence data into a computer in which SNP information is stored. In a more preferred embodiment, the input is made from a terminal via the Internet, SNPs are detected on the server, and the detection results can be output to the terminal via the Internet.

[0019] The subject whose skin characteristics are detected according to the present invention may be of any race. On the other hand, since the types and abundances of SNPs can vary among races, it is preferable to identify the race and then identify the SNPs. In particular, when skin characteristics are detected with respect to human skin color, the subject race is preferably Mongoloid.

[0020] As skin characteristics, it is possible to determine at least one selected from the group consisting of skin shape characteristics, skin texture, and skin color characteristics. The relationship between SNPs and these skin characteristics is such that the presence of SNPs in a heterozygous or homozygous state can act negatively or positively on these skin characteristics. An SNP score can be calculated based on the number of SNPs that act negatively and the number of SNPs that act positively. As an example, the SNP score can be calculated by subtracting the number of SNPs that act negatively from the number of SNPs that act positively. As another example, conversely, the SNP score may be calculated by subtracting the number of SNPs that act positively from the number of SNPs that act negatively. By determining in advance the relationship between the skin characteristics and the SNP score, the skin characteristics in the subject can be determined based on the calculated SNP score.

[0021] When the skin characteristic is a skin shape characteristic, the following: At least one SNP selected from the group consisting of rs1256062, rs10515552, rs1107946, rs12785878, rs12931267, rs1501299, rs1799750, rs1800629, rs2285053, rs3760776, rs12051272, rs1030868, rs10741657, rs11057830, rs11234027, rs1126643, rs11568737, rs1485766, rs1540771, rs16891982, rs17577, rs1799724, rs1800012, rs1801133, rs1993116, rs2010963, rs2060793, rs2108622, rs2228479, rs2232228, rs2234693, rs2241145, rs2246416, rs2287074, rs3785079, rs3829251, rs3865188, rs4065, rs41281112, rs492602, rs6058017, rs7501331, rs7799039, rs8326, and rs964184 is used. The skin shape characteristics can be further subdivided into wrinkles, texture, and firmness. When the skin shape characteristic is wrinkles, at least one SNP selected from the group consisting of the following: rs1800629, rs1107946, rs1501299, rs10515552, rs12785878, rs12051272, rs1126643, rs1256062, rs1485766, rs1799750, rs2234693, rs2246416, rs3760776, rs3865188, rs4065, rs6058017, and rs964184 is used. When the skin shape characteristic is texture, at least one SNP selected from the group consisting of the following: rs1256062, rs1799750, rs12931267, rs11057830, rs1107946, rs11234027, rs16891982, rs17577, rs1799724, rs1800012, rs2010963, rs2108622, rs2232228, rs3785079, rs3829251, rs7501331, rs7799039 is used.When the muscle shape characteristic is firmness, at least one SNP selected from the group consisting of the following: rs1256062, rs3760776, rs12931267, and rs2285053 is used. The relationship between these SNPs and the genes in which the SNPs are present is as follows. [Table 1] Among these SNPs, when a SNP with a negative (-) indication of the above action is present in heterozygous or homozygous form, it can be determined that wrinkles are less likely to form. On the other hand, when a SNP with a positive (+) indication of the above action is present in heterozygous or homozygous form, it can be determined that wrinkles are likely to form.

[0022] The SNP score for wrinkle determination is represented by the following formula as an example, and based on such a SNP score, the wrinkle state can be determined. [Equation] [Equation] [Equation] On the other hand, the SNPs selected for the determination of the SNP score (wrinkles) may be arbitrarily removed.

[0023] When the muscle characteristic is the skin color characteristic, the following: At least one SNP selected from the group consisting of rs1030868, rs10741657, rs1107946, rs12785878, rs1799750, rs2046571, rs2241145, rs2246416, rs2285053, rs2287074, rs3760776, rs3829251, rs6058017, rs74653330, rs8326, rs833061, rs10515552, rs10882272, rs11057830, rs11234027, rs1126643, rs12272004, rs1256062, rs12913832, rs1485766, rs1501299, rs1540771, rs17577, rs1799724, rs1800629, rs1993116, rs2010963, rs2060793, rs2227564, rs2228479, rs2232228, rs2282679, rs2298585, rs2987983, rs3785079, rs3865188, rs4065, rs41281112, rs4654748, rs4880, rs492602, rs7201, rs9340799, and rs964184 is used. Skin color characteristics can be further subdivided into skin base color, skin color in the ultraviolet-exposed area, freckles, brightness, and yellowness. When the skin color characteristic is the skin base color, at least one SNP selected from the group consisting of rs3760776, rs2246416, rs2241145, rs10741657, rs6058017, rs2287074, rs74653330, rs1256062, rs17577, rs3865188, rs41281112, and rs8326 is used. When the skin color characteristic is the skin color in the ultraviolet-exposed area of the skin, at least one SNP selected from the group consisting of rs2241145, rs6058017, rs1799750, rs1030868, rs2287074, rs2046571, rs2285053, rs10741657, rs2246416, rs1107946, rs7201, and rs74653330 is used.When the skin color characteristic is a stain, at least one SNP selected from the group consisting of the following: rs1030868, rs12785878, rs1799750, rs2046571, rs2241145, rs3829251, rs8326, rs833061, rs10515552, rs10741657, rs10882272, rs11057830, rs11234027, rs12272004, rs1256062, rs1485766, rs1501299, rs1540771, rs1799724, rs1800629, rs1993116, rs2010963, rs2060793, rs2227564, rs2232228, rs2246416, rs2282679, rs2298585, rs2987983, rs4065, rs4880, rs492602, rs6058017, rs7201, and rs964184 is used. When the skin color characteristic is brightness, at least one SNP selected from the group consisting of the following: rs2285053, rs6058017, rs74653330, rs2246416, rs11057830, rs1126643, rs1799724, rs2228479, rs2232228, rs4654748, rs833061, and rs9340799 is used. When the skin color characteristic is yellowness, at least one SNP selected from the group consisting of the following: rs10741657, rs6058017, rs2241145, rs2285053, rs1799750, rs1030868, rs2246416, rs1107946, rs1126643, rs12913832, rs17577, rs3785079, rs492602, rs74653330, rs833061, and rs9340799 is used.

[0024] The relationship between the SNP related to the skin color characteristic and the gene in which the SNP exists is as follows:

Table 2

[0025] Among these SNPs, SNPs with a negative (-) indication of the above effect can be determined to tend to decrease when the respective measured values of skin color characteristics are present in heterozygous or homozygous form, while SNPs with a positive (+) indication of the above effect can be determined to tend to increase when the respective measured values of color characteristics are present in heterozygous or homozygous form. Skin color characteristics can be further subdivided into, for example, freckles (freckles, average freckle area), melanin content (cheek melanin, inner upper arm melanin), skin color (brightness of cheek, yellowness of cheek), etc. according to the above table. When SNPs indicated as positive for freckles are present in heterozygous or homozygous form, there is a tendency for freckles to be more likely to appear and their size to be larger. When SNPs indicated as positive for melanin content are present in heterozygous or homozygous form, there is a tendency for the melanin content to increase. When SNPs indicated as positive for skin color are present in heterozygous or homozygous form, there is a tendency for the skin color to become darker.

[0026] More specifically, for freckles, when having SNPs indicated as negative (-), there is a tendency for freckles to become lighter, and when having SNPs indicated as positive (+), there is a tendency for freckles to become darker. For the average freckle area, when having SNPs indicated as negative (-), there is a tendency for the average freckle area to become narrower, and when having SNPs indicated as positive (+), there is a tendency for the average freckle area to become wider. For cheek melanin and inner upper arm melanin, when having SNPs indicated as negative (-), there is a tendency for the melanin content to decrease, and when having SNPs indicated as positive (+), there is a tendency for the melanin content to increase. For the brightness of the cheek, when having SNPs indicated as negative (-), the brightness of the cheek becomes darker, and when having SNPs indicated as positive (+), the brightness of the cheek becomes brighter. For the yellowness of the cheek, when having SNPs indicated as negative (-), the yellowness becomes lighter, and when having SNPs indicated as positive (+), there is a tendency for the yellowness to become darker.

[0027] Freckles mainly refer to the deposition of pigments that occur mainly on the face. The main cause of freckles is ultraviolet rays. Ultraviolet rays increase the activity of melanocytes, resulting in an increased amount of melanin production compared to other parts. In addition to ultraviolet rays, stress, lack of sleep, and imbalance of female hormones also affect the formation of freckles. Freckles include inflammatory pigmentation, senile lentigines, melasma, and ephelides. The average freckle area indicates the size when freckles occur. Freckles can be determined visually or by any other method. For example, the index value of freckles can be determined using equipment such as Visia Evolution.

[0028] The inner side of the upper arm is a place that is less affected by ultraviolet rays. Therefore, SNPs related to the amount of melanin on the inner side of the upper arm indicate the genetic tendency regarding the skin color, in other words, the skin color in a state without the influence of ultraviolet rays. For example, it can be said that a subject with a genetically high amount of melanin on the inner side of the upper arm has a dark skin color. On the other hand, the face is a place that is constantly affected by ultraviolet rays. Therefore, SNPs related to the amount of melanin on the face indicate the ease of darkening due to the influence of ultraviolet rays.

[0029] The brightness and yellowness of the cheeks are related to skin dullness. The causes of dullness include the amount of melanin, blood circulation, dryness, and aging (protein denaturation such as glycation and carbonylation). The brightness and yellowness of the cheeks can be measured using a spectrophotometer.

[0030] The SNP score for determining skin color characteristics is represented by the following formula as an example, and based on such an SNP score, skin color characteristics can be determined.

Number

Number

Number

Number

Number

Number

[0031] When the skin characteristic is skin texture, the following: At least one SNP selected from the group consisting of rs2987983, rs1050565, rs11057830, rs12931267, rs17822931, rs1800414, rs1800629, rs2285053, rs3760776, rs3829251, rs74653330, rs7501331, rs1030868, rs10515552, rs1061622, rs10882272, rs1107946, rs1126643, rs2241145, rs2282679, rs41281112, rs6058017, rs7201, rs7799039, rs8110862, rs9340799, rs12377462, rs1485766, rs1501299, rs16891982, rs17577, rs1800012, rs2228479, rs3785079, rs1667255, rs2046571, rs2227564, rs2246416, rs4065, rs4880, rs492602, and rs964184 is used. Skin quality can be further subdivided into sebum amount, moisture amount, and skin barrier function. When the skin quality is sebum amount, at least one SNP selected from the group consisting of the following: rs2987983, rs74653330, rs12931267, rs10882272, rs1667255, rs2046571, rs2227564, rs2246416, rs4065, rs4880, rs492602, rs6058017 and rs964184 is used. When the skin quality is moisture amount, at least one SNP selected from the group consisting of the following: rs7501331, rs3760776, rs3829251, rs17822931, rs1126643, rs12377462, rs1485766, rs1501299, rs16891982, rs17577, rs1800012, rs2228479, rs2282679, rs3785079, rs7201, and rs9340799 is used.When the skin quality is the skin barrier function, at least one SNP selected from the group consisting of the following: rs1050565, rs17822931, rs1800414, rs2285053, rs3829251, rs1800629, rs11057830, rs1030868, rs10515552, rs1061622, rs10882272, rs1107946, rs1126643, rs2241145, rs2282679, rs41281112, rs6058017, rs7201, rs74653330, rs7799039, rs8110862, and rs9340799 is used. The relationship between these SNPs and the genes in which the SNPs are present is as follows:.

Table 3

[0032] The SNP score related to skin function determination is represented by the following formula, and based on such SNP score, the skin function can be determined. Each characteristic of the subdivided skin function can be determined based on the following SNP score.

Number

Number

Number

Number

Number

[0033] In another aspect of the present invention, the present invention relates to a computer for determining skin characteristics. Such a computer can execute the method for determining skin characteristics described above. In a further method of the present invention, the present invention also relates to a method or program for controlling a computer for determining skin characteristics of the present invention, and a storage medium storing the program. The computer of the present invention includes a storage unit, an input unit, an output unit, and a processing unit.

[0034] The storage unit has a memory device such as RAM, ROM, flash memory, a fixed disk device such as a hard disk drive, or a portable storage device such as a flexible disk, an optical disk, etc. The storage unit stores data and instructions input from the input unit, calculation processing results performed by the processing unit, and programs, databases, etc. used for various processes of the computer. The computer program may be installed via a computer-readable recording medium such as a CD-ROM, a DVD-ROM, or via the Internet. The computer program is installed in the storage unit using a known setup program or the like. In the present invention, the storage unit includes the following: Stores information on at least one SNP selected from the group consisting of rs1030868, rs1050565, rs10515552, rs10741657, rs11057830, rs1107946, rs1256062, rs12785878, rs12931267, rs1501299, rs17822931, rs1799750, rs1800414, rs1800629, rs2046571, rs2241145, rs2246416, rs2285053, rs2287074, rs2987983, rs3760776, rs3829251, rs6058017, rs74653330, rs7501331, rs8326, rs833061, rs11234027, rs16891982, rs17577, rs1799724, rs1800012, rs2010963, rs2108622, rs2232228, rs3785079, rs7799039, rs10882272, rs1485766, rs1540771, rs7201, rs964184, rs1993116, rs2060793, rs2282679, rs12272004, rs2227564, rs2298585, rs4065, rs4880, rs492602, rs12051272, rs1126643, rs2234693, rs3865188, rs11568737, rs1801133, rs2228479, rs41281112, rs1061622, rs8110862, rs9340799, rs12377462, rs1667255, rs12913832, and rs4654748, and information on muscle characteristics associated with the SNP. The information on these SNPs may further store information on SNPs in linkage disequilibrium with the SNP. The information on SNPs includes sequence information, and the information on muscle characteristics associated with the SNP records the type and action of the muscle characteristics, the SNP score, and the multiplier in the case of homozygous presence.

[0035] The input unit includes an interface. The interface may be connected to an operation unit such as a keyboard and a mouse, a communication unit such as a LAN and a port, and an external storage device such as a CD-ROM, a DVD-ROM, a BD-ROM, and a memory stick. Information regarding the SNP and information on skin characteristics related to the SNP may be input from the input unit and stored in the storage unit. Also, the array information of the target is input from the input unit. The input array information may be temporarily stored in the storage unit or sent directly to the processing unit. The array information of the target may be the entire genomic sequence of the target or only a partial sequence of interest. An instruction for processing in the processing unit can be given from the input unit via the operation unit.

[0036] The processing unit detects the presence of SNPs in the array information of the target. More specifically, the processing unit can detect the presence of SNPs in the array information of the target from the SNP array information stored in the storage unit and the array information of the target input from the input unit. The presence of SNPs can be detected by comparing the SNP array information stored in the storage unit with the array information of the target input from the input unit, or by searching for the SNP array information stored in the storage unit in the array information of the target input from the input unit. The processing unit executes various arithmetic operations according to the program stored in the storage unit. The arithmetic operations are performed by the CPU included in the processing unit. This CPU includes functional modules for controlling the input unit, the storage unit, and the output unit, and can perform various controls. Each of these units may be composed of an independent integrated circuit, microprocessor, firmware, etc. Information regarding the presence of SNPs detected by the processing unit may be temporarily stored in the storage unit, or the processing unit can directly read out from the storage unit the information on skin characteristics related to the SNP based on the presence of the SNP. Also, when multiple SNPs are present, an SNP score can be calculated based on the SNP information. Next, the processing unit processes the read-out information on skin characteristics to output it from the output unit.

[0037] The output unit is configured to output the skin characteristic information and / or SNP scores stored in the storage unit for the SNPs detected by performing arithmetic processing in the data processing unit. The output unit may be a display device such as a liquid crystal display that directly displays the result of the arithmetic processing, an output means such as a printer, or an interface unit for outputting to an external storage device or outputting via a network.

[0038] In a preferred aspect of the present invention, the computer of the present invention constitutes a server, and the input unit and the output unit are each connected to a network via an interface unit. In this case, genomic information or sequence information of a part of the genome can be provided from an individual terminal connected to the network, and the presence of SNPs processed by the server in the provided sequence information can be detected, the skin characteristics can be determined, and the determined skin characteristics can be output to the terminal.

[0039] Although it is possible to determine skin characteristics by detecting a single SNP, from the viewpoint of achieving better sensitivity, it is preferable to detect a plurality of SNPs and determine skin characteristics. In order to determine skin characteristics based on the detection of a plurality of SNPs, as an example, it is performed by clarifying whether the SNP has a positive or negative effect on the skin characteristic and assigning points according to its presence to calculate an SNP score. By determining in advance the relationship between the SNP score and the skin characteristic, the skin characteristic can be determined from the SNP score.

[0040] In the examples, based on the SNP information obtained from 200 volunteers and the relationship with skin characteristics, the relationship between the SNP score and skin characteristics is shown (Figs. 3 to 16). These SNP scores vary depending on the population and the SNPs selected. Although not intended to be limiting, for example, for wrinkles, when the SNP score is 2 or more, more preferably 3 or more, it can be determined that wrinkles are likely to occur due to aging. For example, for freckles, when the SNP score is 2 or more, more preferably 4 or more, it can be determined that freckles are likely to occur due to aging. For example, for skin texture, when the SNP score is 2 or more, more preferably 3 or more, it can be determined that the skin texture is likely to deteriorate due to aging.

[0041] When skin characteristics are determined by the skin characteristic determination method of the present invention, counseling can be performed based on information about such skin characteristics. Therefore, one aspect of the present invention also relates to a counseling method. In such counseling, advice can be provided regarding lifestyle habits and the selection of cosmetics and supplements to be used. As an example, among the skin color characteristics, the amount of melanin in the upper arm is related to the natural skin color of the person, and the amount of melanin on the face is related to the skin color affected by ultraviolet rays. Therefore, through SNP analysis, a subject with a low amount of melanin in the upper arm and an increased amount of melanin on the face can be determined to be a subject who is fair-skinned but vulnerable to ultraviolet rays and thus requires more care against ultraviolet rays. For such a subject, it is possible to propose a lifestyle habit of avoiding ultraviolet rays and to propose using cosmetics containing a stronger ultraviolet protection agent.

[0042] When it is determined that wrinkles are likely to occur, it is possible to provide cosmetics or supplements containing components that can enhance the production of collagen fibers and elastic fibers such as collagen and elastin, and / or components that can suppress the degradation of elastic fibers, such as matrix metalloproteinase inhibitors. Such components include extracellular matrix degradation inhibitors, for example, matrix metalloproteinase inhibitors, and more specifically, collagenase inhibitors. Specific components include retinol, chickpea extract, mangosteen extract, etc. (Advances in Evaluation Techniques and Future Prospects of Cosmetic Usefulness, Yakujutsu Shimbunsha, (2001), Section 7, Anti-wrinkle Cosmetics, pp. 162-177).

[0043] When it is determined that problems related to skin color characteristics such as spots are likely to occur, it is possible to provide cosmetics or supplements containing components having a UV-cutting effect, a melanin production inhibitory effect, and / or a promoting effect on keratin turnover. Such components include, for example, UV protectants, vitamin C derivatives, hydroquinone, tranexamic acid, potassium 4-methoxysalicylate, arbutin, kojic acid, lucinol, vitamin C derivatives, etc. (Advances in Evaluation Techniques and Future Prospects of Cosmetic Usefulness, Yakujutsu Shimbunsha, (2001), Section 6, Whitening Cosmetics, pp. 144-161). Also, it is possible to propose appropriate makeup bases, cosmetics, and makeup methods.

[0044] When it is determined that skin functions such as texture, firmness, sebum, moisture content, and skin barrier function are inferior, it is possible to provide cosmetics or supplements containing components that can enhance the skin functions. Agents for improving texture and firmness, sebum-reducing agents, moisture content-increasing promoters, skin barrier function-improving agents, etc. are each known. Such components include, for example, moisturizers, tranexamic acid, chickpea extract, etc.

[0045] In another aspect of the present invention, it also relates to a kit for determining skin characteristics. The kit includes the following: At least one SNP selected from the group consisting of rs1030868, rs1050565, rs10515552, rs10741657, rs11057830, rs1107946, rs1256062, rs12785878, rs12931267, rs1501299, rs17822931, rs1799750, rs1800414, rs1800629, rs2046571, rs2241145, rs2246416, rs2285053, rs2287074, rs2987983, rs3760776, rs3829251, rs6058017, rs74653330, rs7501331, rs8326, rs833061, rs11234027, rs16891982, rs17577, rs1799724, rs1800012, rs2010963, rs2108622, rs2232228, rs3785079, rs7799039, rs10882272, rs1485766, rs1540771, rs7201, rs964184, rs1993116, rs2060793, rs2282679, rs12272004, rs2227564, rs2298585, rs4065, rs4880, rs492602, rs12051272, rs1126643, rs2234693, rs3865188, rs11568737, rs1801133, rs2228479, rs41281112, rs1061622, rs8110862, rs9340799, rs12377462, rs1667255, rs12913832, and rs4654748, or an SNP in linkage disequilibrium therewith, and a nucleic acid reagent for detecting the same. Such a kit may further include a nucleic acid extraction reagent and a purification reagent. It may also include an instruction manual for explaining the relationship between the detected SNP and the skin condition.

[0046] As such a nucleic acid reagent, as an example, it includes primers capable of selectively amplifying SNPs, DNA polymerase, dNTPs, and optionally an amplification buffer. Primers capable of amplifying SNPs can be arbitrarily designed for each SNP.

[0047] When using a nucleic acid probe as a nucleic acid reagent, the kit may further include a probe detection reagent. Such a nucleic acid probe may use an unfixed probe, or a probe fixed on a DNA chip can be used to simultaneously detect a plurality of SNPs. Such a nucleic acid probe may be labeled so as to be able to detect a specific SNP.

[0048] All documents mentioned in this specification are hereby incorporated by reference in their entirety.

[0049] The embodiments of the present invention described below are for illustrative purposes only and do not limit the technical scope of the present invention. The technical scope of the present invention is limited only by the description of the claims. Changes to the present invention, for example, addition, deletion, and substitution of the constituent elements of the present invention, can be made on the condition that the gist of the present invention is not deviated from.

Examples

[0050] Measurement of muscle characteristic values As skin characteristic values, 200 female volunteers aged 35 to 59 were targeted, and the wrinkle state, spot state, skin color (amount of facial melanin, amount of melanin in the underlying skin (inner upper arm), brightness, yellowness), and skin state (moisture content, barrier function, sebum amount, firmness, texture state) of the skin were measured. For each measurement, for the wrinkle state and the spot state, Visia Evolution (manufactured by Canfield Scientific) was used, and the index values of wrinkles and spots were calculated from the photographed images by a dedicated analysis method and used for the analysis. Skin color was analyzed using a spectrocolorimeter CM-700d (Konica Minolta), and the amount of melanin, brightness (L * · colorimetric value), and yellowness (b *· The colorimetric values were measured. In addition, the skin color of the inner side of the upper arm, which is a part not exposed to sunlight, was also measured, and the amount of melanin was calculated. The skin condition was measured using a dedicated commercially available device for the water content of the stratum corneum (Corneometer), transepidermal water loss (barrier function) (Vapometer), sebum amount (Sebumeter), and skin elasticity (Cutometer). The texture condition was measured using Skinvisiom II, an original measuring device, and dedicated analysis software to measure the degree of texture disorder.

[0051] Genetic analysis (SNP genotyping) Saliva was used as the gene analysis specimen. Saliva was collected using Oragene (registered trademark) DNA OG - 500 (DNA Genotek Inc.) to stabilize the DNA. DNA was purified from the saliva, and SNP genotyping was performed using a DNA array to obtain information on pre - selected SNPs. The SNPs to be analyzed were selected based on past dermatological findings as those expected to affect skin characteristic values.

[0052] Methods of statistical processing The relationship between skin characteristic values and SNP genotypes was determined by performing multiple comparisons, multiple regression analysis, statistical analysis of odds ratios, cases where prediction intervals were set with an optimal regression model, and control analysis. Furthermore, the relationship between multiple SNP genes related to skin characteristics was evaluated by performing covariance structure analysis (SEM) and decision tree analysis, and an attempt was made to standardize the influence of SNP genes on skin characteristic values.

[0053] Multiple comparison analysis Regarding the pairs of skin characteristic values and gene SNPs, an analysis was conducted to determine which genotype SNPs differed in the distribution of skin characteristic values. For quantitative data, a multiple comparison test was performed using Tukey multiple comparisons. For qualitative data, a chi - square test and Fisher's exact probability test were applied. The SNPs selected by the multiple comparison analysis are shown in Table 4 below.

Table 4

[0054] Multiple regression analysis As a result of the simple regression analysis, it was shown that many characteristic values were correlated with age (data not shown). Therefore, in order to separate the aging effect and the genetic effect, a multiple regression analysis was performed with genetic factors and age (numerical values) as variables. For the relationships in which the coefficients of the genetic factors were significant, the standardized partial regression coefficients and p-values were calculated. An SNP with a positive sign of the standardized partial regression coefficient indicates that the skin characteristic value increases due to the mutation, and a negative sign indicates that the skin characteristic value decreases due to the mutation. The SNPs selected by the multiple regression analysis are shown in Table 5 below.

[0055]

Table 5

[0056] Odds ratio A threshold was set to divide the skin characteristic data into two groups, and a contingency table was created in combination with the SNP genotypes. Since the skin characteristic values change with age, the threshold also changed with age. Here, the top 1 / 4 in rank of the skin characteristic values within a certain age range was defined as the high group, and the bottom 1 / 4 as the low group, and a comparison was made between these two groups. The selection criteria for the control group and the risk group were as follows: when the skin characteristic value increases with aging, the increasing group was set as the risk group; conversely, when it decreases, the decreasing group was set as the risk group for analysis. For each SNP, samples of two genotypes were selected, a 2×2 contingency table was created for the control group and the risk group, and a statistical test was performed. The "same age" in the selection of the control group and the risk group was defined as ±5 years of one's own age. The combinations of skin characteristic values and SNPs that were significant in the Fisher's exact probability test among the odds ratios of the wild type and the heterozygous or homozygous types are shown in Table 6 below.

[0057]

Table 6

[0058] Covariance structure analysis (SEM) analysis SEM analysis is a method for modeling the relationship between continuous variables and is a model analysis that integrates multiple regression analysis and factor analysis. Categorical variables can be applied if they are replaced with dummy variables. Model variables are observed variables and latent variables (construct concepts). Skin characteristic value data, age, and SNP polymorphism data are observed variables, and SNP polymorphism data was treated as one dummy variable after being replaced with Wild→0, Hetero→1, Homo→2. The model notation of SEM used the lavaan notation that enables flexible model description.

[0059] Procedures of analysis (1) Define the model. (2) Estimate the model parameters (population parameters) so as to maximize the variance structure of the sample data. (3) Check the goodness-of-fit index of the model (an index indicating how well the variance structure of the sample data was explained). (4) Check the magnitude and reliability (p-value) of the model parameters. (5) If the goodness-of-fit and parameters are good, the analysis ends. (6) If there is a model variable with good goodness-of-fit but low reliability, the analysis in (1) to (4) was performed and compared using the model excluding it. If the goodness-of-fit is poor, the model was improved with reference to the modification index (an index indicating what kind of relationship should be added to the model to improve the goodness-of-fit), and the analysis in (1) to (4) was performed and compared.

[0060] Decision tree analysis In decision tree analysis, the continuous skin characteristic value was used as the target variable, and the branching condition was determined so as to minimize the ratio of the between-class variance and within-class variance of the target variable in the two divided groups. Since age was included in the branching factor, age-group analysis was not performed, and modeling was carried out for all samples. The model variables were (1) Target variable (dependent variable): Skin characteristic value (continuous value) (2) Explanatory variables (independent variables): Age classes in 5-year increments, SNP polymorphism were used. Procedures of analysis (1) Determine the combination of the target variable (skin characteristic value) and the explanatory variable (SNP). (2) In the decision tree analysis, continue splitting so that the complexity (CP: Complexity Parameter) decreases. Initially, analyze under the condition of continuing to split as long as the CP decreases. (3) Calculate the error rate of the model for each branching condition using the n-fold cross-validation method. The n-fold cross-validation method divides the data into n sets, uses n - 1 of these sets to create a decision tree, discriminates the remaining 1 set of data, and calculates the error rate of the result. Perform n evaluations by swapping the test data. (4) Adopt the Min + 1SE method as the stopping condition. (5) Use the tree created up to the splitting point of the stopping condition as the decision tree.

[0061] The genes selected from the SEM analysis and the decision tree analysis are shown in Table 7 below.

Table 7

[0062] Examination of standardization Regarding the quantification of the influence of SNPs on skin characteristic values from the previous analysis results, we examined the relationship between SkinXX and SnpYY taken up in this section by simply counting points. An increasing factor is +1 and a decreasing factor is -1. For each characteristic value, select the SNPs shown below, and the calculation formula for the score, the frequency distribution of the score, and the BoxPlot of the skin characteristic values for each score are shown in Figures 3(A) to 16(A).

[0063] The SNPs selected for quantification are shown in Table 8 below.

Table 8-1

Table 8-2

[0064] Analysis of SIM Among the skin characteristics, the analysis of freckles is based on the following formula:

Number

[0065] Analysis of SIM average area Among the skin characteristics, the analysis of the average freckle area was performed using the following formula:

Number

[0066] Analysis of buccal melanin Among the skin characteristics, the analysis of the cheek melanin was performed using the following formula:

Number

[0067] Analysis of medial upper arm melanin Among the skin characteristics, the analysis of the inner upper arm melanin was performed using the following formula:

Number

[0068] Analysis of cheek brightness Among the skin characteristics, the brightness of the cheek was analyzed using the following formula:

Number

[0069] Analysis of cheek yellowness Among the skin characteristics, the yellowness of the cheek was analyzed using the following formula:

Number

[0070] Analysis of wrinkles Among the skin characteristics, the wrinkle analysis was performed using the following formula:

Number

[0071] Analysis of texture Among the skin characteristics, the texture analysis was performed using the following formula:

Number

[0072] Analysis of firmness Among the muscle characteristics, the analysis of stiffness was performed using the following formula:

Equation

[0073] Analysis of sebum - forehead Among the muscle characteristics, the analysis of sebum - forehead was performed using the following formula:

Equation

[0074] Analysis of moisture content - cheek Among the muscle characteristics, the analysis of moisture content - cheek was performed using the following formula:

Equation

[0075] Analysis of moisture content - arm Among the muscle characteristics, the analysis of moisture content - arm was performed using the following formula:

Equation

[0076] Analysis of barrier - cheek Among the skin characteristics, the barrier - cheek analysis was performed using the following formula:

Equation

[0077] Analysis of barrier - arm Among the skin characteristics, the barrier - arm analysis was performed using the following formula:

Equation

[0078] Case where prediction intervals are set with the optimal regression model, control analysis The number of subjects was increased to the number of subjects shown in Table 9 below, and further analysis was carried out. Regarding the pairs of skin characteristic values and genotype SNPs, it was analyzed which genotype SNPs differed in the distribution of skin characteristic values. For each skin characteristic, the optimal regression model shown in Table 10 was set from the plot of age and each measured value, and the width prediction interval of the standard deviation (σ) was determined. The sample group that deviated above the width prediction interval was defined as the high - value group, and the sample group that deviated below was defined as the low - value group. The high - value group and the low - value group were regarded as "cases", and the others were regarded as "controls", and the chi - square test was applied, and the selected SNPs are shown in Table 11 below. The detection of the influence of SNPs was analyzed in two ways: dominance (dominant) and recessiveness (recessive). Dominance was defined as (wild + hetero) vs homo, and recessiveness was defined as wild vs (hetero + homo).

Table 9

[0079]

Table 10

Table 11-1

Table 11-2

Table 11-3

Table 11-4

Table 11-5

Claims

**Claim 1** A step of detecting rs2246416 as an SNP, A step of determining skin color characteristics based on an SNP group including the detected SNP A method for determining skin color characteristics, comprising the above steps. **Claim 2** The determination method according to Claim 1, wherein the skin color characteristics are selected from the group consisting of skin base color, skin color of the UV-exposed area, freckles, brightness, and yellowness. **Claim 3** A beauty counseling method based on skin characteristics determined by the method according to Claim 1 or 2. **Claim 4** A method for providing a cosmetic, characterized by selecting a cosmetic according to the skin characteristics determined by the method according to Claim 1 or 2. **Claim 5** A method for providing a supplement for beauty, characterized by selecting a supplement according to the skin characteristics determined by the method according to Claim 1 or 2.

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