Biomarkers for inducing left ventricular hypertrophy by hypertension

Abstract

The invention belongs to the field of biological medicines, and particularly relates to a group of biomarkers for inducing left ventricular hypertrophy by hypertension. In particular, the marker is one or more of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3 and Cdca3, and the molecular marker is one or more of the following molecular markers: the molecular marker is one or more of the following molecular markers: Ankrd1, Birc5, Nuf2, C1qtnf6 and Cdca3; up-regulation of any one or more of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3 and Cdca3 represents that a hypertensive patient suffers from left ventricular hypertrophy, or represents that a subject suffers from left ventricular hypertrophy induced by the hypertensive patient.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and specifically relates to a group of biomarkers for hypertension-induced left ventricular hypertrophy. Background Art

[0002] It is known that both hypertension and left ventricular hypertrophy are independent risk factors for cardiovascular and cerebrovascular diseases (such as coronary atherosclerotic heart disease, congestive heart failure, stroke, or transient ischemic heart disease and even sudden death). Left ventricular hypertrophy (LVH) is a myocardial change phenomenon characterized by thickening of the ventricular wall, increased myocardial weight, and myocardial remodeling. The lower left heart chamber, also known as the left ventricle, is the main pumping chamber of the heart. When left ventricular hypertrophy occurs, the thickened heart wall may become stiff, and the blood pressure in the heart increases, making it more difficult for the heart to pump blood effectively. Hypertension is the most important cause of left ventricular hypertrophy; in addition, factors such as the elderly, obesity, genetics, alcohol consumption, and high-salt diet are also risk factors for left ventricular hypertrophy. The weighted risk of hypertension with left ventricular hypertrophy will be exacerbated and promote the occurrence and progression of cardiovascular and cerebrovascular diseases. Therefore, hypertension with left ventricular hypertrophy is a target organ damage that must be concerned about.

[0003] Asia is a region with a high prevalence of hypertension. The age-adjusted prevalence of hypertension is 20% - 30%. Affected by various factors, the incidence of hypertension combined with left ventricular hypertrophy and left heart failure has been increasing year by year, and the growth rate is faster than that in Western countries. Patients with hypertension combined with left ventricular hypertrophy face greater risks of cardiovascular events, arrhythmia, atrial fibrillation, cerebrovascular events, and all-cause death.

[0004] The immune response plays an important role in hypertension-induced left ventricular hypertrophy, but there is still a lack of systematic and comprehensive methods to study the mechanism relationship and new therapeutic targets between them. Summary of the Invention

[0005] The present invention aims to provide marker genes for diagnosing / predicting hypertension-induced left ventricular hypertrophy, so as to achieve early diagnosis of hypertension-induced left ventricular hypertrophy. The specific technical solutions are as follows:

[0006] In a first aspect, the present invention provides the use of a reagent for detecting the expression level of a biomarker in the preparation of a product for diagnosing and predicting a disease,

[0007] wherein the disease is hypertension-induced left ventricular hypertrophy (LVH),

[0008] and the biomarker is one or more of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3.

[0009] Preferably, the biomarker is a combination of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3.

[0010] Specifically, Ankrd1 is Ankyrin repeat domain 1 (ANKRD1), with Ensembl ID ENSG00000148677.

[0011] Specifically, Birc5, also known as survivin, is an apoptosis inhibitor protein, with Ensembl ID ENSG00000089685.

[0012] Specifically, NUF2 is a core component of the NDC80 complex, with Ensembl ID ENSG00000143228.

[0013] Specifically, C1qtnf6 is a C1q / tumor necrosis factor-related protein 6, with Ensembl ID ENSG00000133466.

[0014] Specifically, the Ensembl ID of Fcgr3 (FCGR3B) is ENSG00000162747.

[0015] Specifically, Cdca3 is cell division cycle associated protein 3, with Ensembl ID ENSG00000111665.

[0016] Specifically, the upregulation of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3 all indicates the occurrence of left ventricular hypertrophy in hypertensive patients, or indicates the occurrence of left ventricular hypertrophy induced by hypertensive patients in a subject. That is, by detecting a sample from a subject, if any one or more of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3 are upregulated, it can be diagnosed as a patient or predicted to have a high risk of disease.

[0017] Specifically, the "increase" or "upregulation" amount or level of the biomarker refers to the amount being equal to or greater than the biomarker expression level in the healthy control group, and the biomarker is overexpressed at least 1.5 times relative to the control expression level, such as at least 1.6 times, 1.7 times, 1.8 times, 1.9 times, 2.0 times, 2.1 times, 2.2 times, 2.3 times, 2.4 times, 2.5 times, 2.6 times, 2.7 times, 2.8 times, 2.9 times, 3.0 times, 3.1 times, 3.2 times, 3.3 times, 3.4 times, or 3.5 times or more.

[0018] The sample of a subject of the term "healthy control group" means a subject or group of subjects diagnosed by a doctor as not suffering from a clinical disease related to left ventricular hypertrophy induced by hypertensive patients based on qualitative or quantitative test results.

[0019] The terms "subject" and "patient" are used interchangeably herein. In certain embodiments, the subject has a disease, or is at risk of having the above disease, which is left ventricular hypertrophy induced by hypertension.

[0020] Preferably, the sample of the subject may refer to a composition obtained from or derived from a subject (e.g., an individual of interest), which contains cells and / or other molecular entities to be characterized and / or identified according to physical, biochemical, chemical, and / or physiological characteristics. Samples include, but are not limited to, tissue samples (e.g., heart tissue samples), primary or cultured cells or cell lines, cell supernatants, cell lysates, platelets, serum, plasma, vitreous humor, lymph fluid, synovial fluid, follicular fluid, semen, amniotic fluid, milk, whole blood, blood-derived cells, urine, cerebrospinal fluid, saliva, sputum, tears, sweat, mucus, tumor lysates, and tissue culture media, tissue extracts such as homogenized tissue, tumor tissue, cell extracts, and combinations thereof.

[0021] More preferably, the sample is a tissue sample, and more preferably, a heart tissue sample.

[0022] Preferably, the reagents for detecting the expression level of the biomarker include reagents for detecting the biomarker by sequencing technology, nucleic acid hybridization technology, nucleic acid amplification technology, and protein immunization technology.

[0023] Furthermore, the reagents include:

[0024] Probes that specifically recognize the biomarker; or

[0025] Primers that specifically amplify the biomarker; or

[0026] Binding agents that specifically bind to the biomarker.

[0027] Preferably, the product includes a kit, a chip, a test strip, high-throughput sequencing, a system, a device, an apparatus.

[0028] Preferably, the reagent may further include an auxiliary detection reagent for mRNA expression level, and the auxiliary detection reagent for mRNA expression level includes, but is not limited to: reaction reagents for visualizing the amplicon corresponding to the primer, such as reagents for visualizing the amplicon by agarose gel electrophoresis, enzyme-linked gel method, chemiluminescence method, in situ hybridization method, fluorescence detection method, etc.; RNA extraction reagent; reverse transcription reagent; cDNA amplification reagent; standard product for preparing the standard curve; positive control product.

[0029] Preferably, the reagent may further include a reagent for assisting in detecting protein expression levels, and the reagent for assisting in detecting protein expression levels includes, but is not limited to, a blocking solution, an antibody diluent, a washing buffer, a color development terminating solution, and a standard product used for preparing a standard curve.

[0030] On the other hand, the present invention provides a method for diagnosing / predicting left ventricular hypertrophy induced by hypertension, the method comprising obtaining expression level data of a biomarker and comparing the data with a threshold value, and when the data is higher than the threshold value, it represents that the subject is a patient or has a high risk of disease.

[0031] The biomarker is one or more of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3.

[0032] It should be noted that the value of the threshold (also known as the cutoff value) may depend on a specific measurement technique. The values given in the specific embodiments of the present invention particularly relate to the measured values using RNA sequencing and qPCR methods. If different methods are used, analog conversion may be required. However, such conversion is within the skill scope of those skilled in the art.

[0033] On the other hand, the present invention provides a computer-readable storage medium having a computer program stored thereon, and when the computer program is executed by a processor, the foregoing method for diagnosing / predicting left ventricular hypertrophy induced by hypertension is implemented.

[0034] Preferably, the computer-readable medium may include a computer storage medium (or non-transitory medium) and a communication medium (or transitory medium). It can be understood that the computer storage medium includes volatile and non-volatile, removable and non-removable media implemented in any method or technology for storing information such as computer-readable instructions, data structures, program modules, or other data. The computer storage medium includes, but is not limited to, RAM, ROM, EEPROM, flash memory or other memory technologies, CD-ROM, digital versatile disc (DVD) or other optical disc storage, magnetic cassette, tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store the desired information and can be accessed by a computer.

[0035] On the other hand, the present invention provides a disease diagnosis / prediction device, the device comprising: a memory and a processor;

[0036] The memory is used for storing program instructions;

[0037] The processor is used to call program instructions, and when the program instructions are executed, it is used to perform the following operations: obtain the gene expression data of the biomarker of the sample to be tested, input the gene expression data into the diagnostic / predictive model constructed by the biomarker, and obtain the diagnostic / predictive result of the sample to be tested;

[0038] The disease is left ventricular hypertrophy induced by hypertension,

[0039] The biomarker is one or more of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3.

[0040] As used in the present invention, "diagnosis" refers to the discovery, judgment, or recognition of the health status or condition of an individual based on one or more symptoms, data, or other information related to the individual. The health status of an individual can be diagnosed as healthy / normal (i.e., free of disease or disorder), or can be diagnosed as unhealthy / abnormal (i.e., having a disease or disorder). The term "diagnosis" includes the early detection of diseases related to diseases; the characterization or classification of diseases; the discovery of the progression, cure, or recurrence of diseases; and the discovery of the response of an individual to a disease after treatment or treatment. In the present invention, the diagnosis of left ventricular hypertrophy induced by hypertension includes distinguishing between individuals with hypertension accompanied by left ventricular hypertrophy and individuals with hypertension without left ventricular hypertrophy, and also includes distinguishing between individuals without left ventricular hypertrophy induced by hypertension and individuals with left ventricular hypertrophy induced by hypertension.

[0041] Advantages and beneficial effects of the present invention:

[0042] The present invention discovers a biomarker for diagnosing left ventricular hypertrophy induced by hypertension. Using this biomarker, diseases can be diagnosed in a timely manner, or the risk of getting sick can be predicted in advance, achieving early detection and early treatment. Description of the Drawings

[0043] Figure 1 It is a graph showing the blood pressure comparison results between the angiotensin II group and the control group.

[0044] Figure 2 It is the magnetic resonance imaging of the angiotensin II group and the control group.

[0045] Figure 3 It is a comparison of the detection results of cardiac structure indexes between the angiotensin II group and the control group.

[0046] Figure 4 It is a graph of the principal component analysis results.

[0047] Figure 5 It is a graph of the differential analysis results.

[0048] Figure 6 It is a clustering dendrogram.

[0049] Figure 7 Graph showing the correlation analysis results between different modules and immune-related parameters.

[0050] Figure 8 It is a Venn diagram of the random forest algorithm and the SVM-RFE algorithm

[0051] Figure 9 It is a result graph of the Lasso regression algorithm.

[0052] Figure 10 It is a diagnostic nomogram for left ventricular hypertrophy composed of key genes.

[0053] Figure 11 It is a calibration curve of the diagnostic nomogram for left ventricular hypertrophy.

[0054] Figure 12 It is the expression levels of key genes obtained by RNA-seq sequencing between two groups.

[0055] Figure 13 It is the ROC curve of a single key gene for diagnosing left ventricular hypertrophy obtained by RNA-seq sequencing.

[0056] Figure 14 It is the expression levels of key genes obtained by qPCR between two groups.

[0057] Figure 15 It is the ROC curve of a single key gene for diagnosing left ventricular hypertrophy obtained by qPCR.

[0058] Figure 16 It is the correlation between the gene expression levels obtained by qPCR and the left ventricular hypertrophy index. Specific implementation manners

[0059] The present invention will be further described below in conjunction with embodiments. The following description is only for the preferred embodiments of the present invention and does not limit the present invention in other forms. Any person skilled in the relevant art may use the disclosed technical content to make equivalent embodiments with equivalent changes. Any simple modification or equivalent change made to the following embodiments based on the technical essence of the present invention without departing from the content of the present invention's solution falls within the protection scope of the present invention.

[0060] Example 1: Establish a model of hypertensive left ventricular hypertrophy

[0061] Wild-type C57BL / 6J male mice (Beijing Vital River Laboratory Animal Technology Co., Ltd., Beijing, China) were housed under specific pathogen-free conditions. The mice were implanted subcutaneously with an osmotic minipump (Alzet MODEL 1007D; DURECT, Cupertino, CA, USA) and injected with normal saline or "pressor dose" angiotensin II (1500 ng / kg / min) for 7 consecutive days. Seven days after the infusion of angiotensin II or normal saline, cine magnetic resonance imaging (CINE) of the heart was performed using a PharmaScan 70 / 16US (7.0T, Bruker, Switzerland) magnetic resonance imaging scanner.

[0062] After the experimental treatment, the mice were anesthetized, the heart was punctured and rinsed with 20 ml of normal saline to remove the blood from the systemic blood circulation. The left ventricle was removed and prepared for further RNA-seq analysis.

[0063] The blood pressure of the mice in the angiotensin II model group and the control group was measured, and the results were as Figure 1 shown. In the angiotensin II model group, the blood pressure increased significantly. Magnetic resonance imaging showed obvious left ventricular hypertrophy in the angiotensin II model group ( Figure 2 ).

[0064] The cine cardiac images were manually measured and calculated using RadiAnt DICOM Viewer 2021.2 software, and further measurement and statistical analysis of cardiac structure and function parameters were performed. One frame of the image at the end-diastolic and end-systolic phases of each layer was selected at the short-axis level of the ventricle. The contour curve of the endocardium of the left ventricle (LV) was manually drawn with a mouse. The papillary muscles were drawn into the blood pool at the papillary muscle level, excluding the left ventricular outflow tract level. The following formula was used for calculation:

[0065]

[0066] Calculate the end-diastolic volume (EDV) and end-systolic volume (ESV) of the left ventricle. Measure the end-diastolic diameter (EDD) and end-systolic diameter (ESD) of the left ventricle at the papillary muscle level; measure the end-diastolic anterior wall thickness (EDAWT), end-diastolic posterior wall thickness (EDPWT), end-systolic anterior wall thickness (ESAWT), and end-systolic posterior wall thickness (ESPWT) at this level.

[0067] The data were statistically analyzed using GraphPad Prism 9.5.1 software. Each parameter was expressed as the mean ± standard deviation. The two-sample t-test was used for comparison between groups. P < 0.05 indicated a significant difference between groups.

[0068] In the angiotensin II-induced model group, the end-diastolic volume, end-systolic volume, end-diastolic diameter, and end-systolic diameter of the left ventricle at the papillary muscle level decreased significantly; the end-diastolic anterior wall thickness, end-diastolic posterior wall thickness, end-systolic anterior wall thickness, and end-systolic posterior wall thickness increased significantly ( Figure 3 ).

[0069] Example 2: Transcriptome sequencing and screening of key genes

[0070] The RNA extraction, quality control, sample preparation, library construction, and sequencing techniques for RNA-Seq were provided by Beijing EK Biotech Co., Ltd.

[0071] The sequencing samples included the angiotensin II perfusion group and the control group, with 16 biological replicates in each group. The RNA concentration, OD260 / 280, and OD260 / 230 of the samples were detected by Nanodrop, and the RNA fragment lengths were detected by Agilent 2100. After the samples passed the detection, Oligo(dT) magnetic beads were used to enrich mRNA. The enriched mRNA was fragmented, and random hexamer primers were added for reverse transcription to synthesize first-strand cDNA. Then, buffer, dNTPs, and DNA polymerase I were added to synthesize second-strand cDNA. Subsequently, the double-stranded cDNA was purified using AMPure XP beads. The synthesized double-stranded cDNA was purified, end-repaired, A-tailed, adapter-ligated, and size-selected using AMPure XP beads. Finally, a cDNA library was constructed by PCR amplification.

[0072] The constructed cDNA library was detected for the effective concentration by Q-PCR and the inserted fragment size by Agilent 2100. The libraries were pooled according to the effective concentration of the libraries and data requirements and sequenced on the machine. Using the Illumina second-generation high-throughput sequencing platform and the PE150 paired-end sequencing method, the basic principle is sequencing by synthesis. The sequencing fragments underwent amplification reactions in fluorescently labeled dNTPs, DNA polymerase, and adapter primers, and the sequencer converted the fluorescent signals released by the labeled dNTPs during the extension of the complementary strand in the sequencing clusters into sequencing peaks to obtain the sequence information of the sequencing fragments.

[0073] In quality control, reads containing adapters, with an N ratio greater than 10%, and with more than 50% of bases having a quality value Q<20 were removed. The transcriptome was aligned in the STAR software, and searches, clustering, and stitching were performed based on the continuously maximum mappable seeds in the uncompressed suffix array. The gene expression levels were quantified in the HISeq software using the union model, and the quantification unit was FPKM. The sequencing samples were grouped and clustered by the PCA algorithm.

[0074] The principal component analysis (PCA) of the RNA-seq data was performed using the R software package "scatterplot3d". The R software packages "limma" and "egdeR" were used to determine the differentially expressed genes between the two groups, with the thresholds of adjusted P<0.05 and the absolute value of log(Foldchange(FC))>0.5. The principal component clustering analysis showed that the gene expression characteristics of the angiotensin II modeling group were significantly different from those of the control group ( Figure 4 ). A total of 1215 differentially expressed genes were obtained through differential analysis ( Figure 5 ).

[0075] Weighted gene co-expression network analysis (WGCNA) was performed using the R package "WGCNA" to identify key modules related to the immune system. First, the cases were hierarchically clustered. Then, the optimal soft power β was selected through scale independence analysis and average connectivity analysis, and gene modules were established. The relationships between the modules and the experimental group, immune score, stromal score, and microenvironment score were explored. The module with the closest relationship to the trait was selected, and a scatter plot of module membership and gene importance was drawn. The clustering dendrogram of WGCNA analysis is shown in Figure 6 as follows, and the correlations between different modules and immune-related parameters are shown in Figure 7 as follows, where turquoise has the most significant positive correlation with experimental grouping, immune score, stromal score, and immune microenvironment score.

[0076] The genes in the target module were tested using support vector machine recursive feature elimination (SVM-RFE) and random forest algorithms through the R package "caret" ( Figure 8 ). Then, through the R package "glmnet", the intersection of the central genes obtained by the two algorithms was screened using the least absolute shrinkage and selection operator (LASSO) regression method. The Venn diagram of the random forest algorithm and the SVM-RFE algorithm shows the genes screened by both. The result graph of screening key genes by the Lasso regression algorithm is shown in Figure 9 as follows. The nomogram for diagnosing left ventricular hypertrophy composed of key genes is shown in Figure 10 as follows. The calibration curve for evaluating the nomogram for diagnosing left ventricular hypertrophy composed of key genes is shown in Figure 11 as follows.

[0077] Example 3: Detect the gene expression level of samples and verify the diagnostic function

[0078] In addition, 30 mice were taken from each of the model group and the control group, and models were constructed according to the method of Example 1 to verify the diagnostic functions of Ankrd1, Birc5, C1qtnf6, Fcgr3, Cdca3, and Nuf2.

[0079] Total RNA was extracted from left ventricular samples of the left ventricular hypertrophy group and the control group using the RNeasy kit according to the manufacturer's instructions (Beyotime, Shanghai, China 456, R0027). Reverse transcription of 1 μg of total RNA was performed using SuperScript II reverse transcriptase (TaKaRa, Japan RR047). Real-time quantitative PCR analysis was performed using SYBR Green Mix (TaKaRa, Japan, RR820) and the ABI 7900HT Real-Time PCR system according to the manufacturer's instructions. It was divided into a two-step PCR standard amplification program, including the first step of pre-denaturation (98 °C for 30 seconds) and the second step of PCR amplification (95 °C for 5 seconds, 60 °C for 30 seconds, 40 cycles), and relative quantification was performed using 2-ΔΔCT;

[0080] The amplification primers for QPCR are as follows:

[0081] Internal reference gene Gapdh:

[0082] Forward primer is 5’-TGGCATTGTGGAAGGGCTCAT-3’ (SEQ ID NO: 1);

[0083] Reverse primer is 5’-CAGCTTTCCAGAGGGGCCAT-3’ (SEQ ID NO: 2);

[0084] Ankrd1:

[0085] Forward primer is 5’-GCTGGTAACAGGCAAAAAGAAC-3’ (SEQ ID NO: 3);

[0086] Reverse primer is 5’-CCTCTCGCAGTTTCTCGCT-3’ (SEQ ID NO: 4);

[0087] Birc5:

[0088] Forward primer is 5’-GAGGCTGGCTTCATCCACTG-3’ (SEQ ID NO: 5);

[0089] Reverse primer is 5’-CTTTTTGCTTGTTGTTGGTCTCC-3’ (SEQ ID NO: 6);

[0090] C1qtnf6:

[0091] Forward primer is 5’-CATCATGGGGATAGCCAGCC-3’ (SEQ ID NO: 7);

[0092] The reverse primer is 5’-GGAGGCCACAGATTCTCCA-3’ (SEQ ID NO: 8);

[0093] Fcgr3:

[0094] The forward primer is 5’-CAGAATGCACACTCTGGAAGC-3’ (SEQ ID NO: 9);

[0095] The reverse primer is 5’-GGGTCCCTTCGCACATCAG-3’ (SEQ ID NO: 10);

[0096] Cdca3:

[0097] The forward primer is 5’-GAGTAGCAGACCCTCGTTCAC-3’ (SEQ ID NO: 11);

[0098] The reverse primer is 5’-TCTCTACCTGAATAGGAGTGCG-3’ (SEQ ID NO: 12);

[0099] Nuf2:

[0100] The forward primer is 5’-TCCCCAGATACAATGTAGCTGA-3’ (SEQ ID NO: 13);

[0101] The reverse primer is 5’-CCGGACTCCATACACTAACTGT-3’ (SEQ ID NO: 14);

[0102] Data processing and visualization were performed using R software (version 3.2) and GraphPad Prism 8.0. Continuous variables were analyzed using the Wilcoxon rank-sum test or the Kruskal-Wallis test. Spearman correlation analysis was used. The significance of large-scale multiple testing was corrected using the Benjamini-Hochberg method. The ROC curve was plotted using the "ROC curve" function in IBM SPSS Statics (version 25).

[0103] The comparison of the expression levels of key genes obtained by RNA-seq between the two groups is as Figure 12 shown, and the ROC curve is as Figure 13 shown. The comparison of the expression levels of key genes obtained by qPCR between the two groups is as Figure 14 shown, and the ROC curve is as Figure 15 shown. Figure 16 This is the correlation between the gene expression levels obtained by qPCR and the left ventricular hypertrophy index.

Claims

1. Use of a reagent for detecting the expression level of a biomarker in the preparation of a product for diagnosing or predicting a disease, wherein the disease is left ventricular hypertrophy induced by hypertension, and the biomarker is one or more of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3; Preferably, the biomarker is a combination of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3.

2. According to the use of claim 1, an upregulation of any one or more of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3 indicates that a hypertensive patient has developed left ventricular hypertrophy, or indicates that a subject has developed left ventricular hypertrophy induced by a hypertensive patient.

3. According to the use of claim 1, the detection is performed on a subject sample, and the sample includes tissue samples, cells or cell lines, cell supernatants, cell lysates, platelets, serum, plasma, vitreous humor, lymph fluid, synovial fluid, follicular fluid, semen, amniotic fluid, milk, whole blood, urine, cerebrospinal fluid, saliva, sputum, tears, sweat, mucus, tumor lysates, and tissue culture media, and combinations thereof. Preferably, the sample is a tissue sample; More preferably, a heart tissue sample.

4. According to the use of claim 1, the reagent includes reagents used in detecting the biomarker by sequencing technology, nucleic acid hybridization technology, nucleic acid amplification technology, and protein immunization technology.

5. According to the use of claim 4, the reagent is a reagent used in sequencing technology and nucleic acid amplification technology for detecting the biomarker.

6. According to the use of claim 1, the reagent includes: a probe that specifically recognizes the biomarker; or a primer that specifically amplifies the biomarker; or a binder that specifically binds to the biomarker.

7. According to the use of claim 6, the reagent further includes an auxiliary reagent for detecting mRNA expression level; Preferably, the reagent further includes an auxiliary reagent for detecting protein expression level.

8. According to the use of claim 1, the product includes a kit, a chip, a test strip, high-throughput sequencing, a system, a device, an apparatus.

9. A computer-readable storage medium having a computer program stored thereon, wherein when the computer program is executed by a processor, a method for diagnosing / predicting left ventricular hypertrophy induced by hypertension is implemented, and the method includes obtaining expression level data of a biomarker and comparing the data with a threshold, and when the data is higher than the threshold, it indicates that the subject is a patient or has a high risk of disease, wherein the biomarker is one or more of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3.

10. A disease diagnosis / prediction device, the device includes: a memory and a processor; the memory is used for storing program instructions; the processor is used for calling the program instructions, and when the program instructions are executed, it is used for performing the following operations: obtaining gene expression data of a biomarker of a sample to be tested, inputting the gene expression data into a diagnosis / prediction model constructed by the biomarker, and obtaining a diagnosis / prediction result of the sample to be tested; The disease is left ventricular hypertrophy induced by hypertension, The biomarker is one or more of Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3.

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