CN105112415A - Genetic locus rs780092 for evaluating type 2 diabetes mellitus risk and detection kit - Google Patents

Abstract

The invention discloses a kit for assessing the risk of type 2 diabetes based on the rs780092 site of the GCKR gene. The present invention also provides an application of a substance for detecting the single nucleotide polymorphism of the rs780092 site in the preparation of a product for evaluating or assisting in evaluating the risk of type 2 diabetes of a person to be tested. The present invention clarifies the influence of blood lipid-related genetic locus rs780092 on the risk of type 2 diabetes, and incorporates it into the risk assessment system, and evaluates the influence of elevated blood lipids on the risk of type 2 diabetes in different individuals according to the blood lipid-related genetic locus rs780092 , in a large-scale prospective cohort, investigated factors applicable to type 2 diabetes risk assessment in a Chinese population. The invention has great significance for solving the problems of comprehensiveness, individualization and accuracy of blood lipid and type 2 diabetes risk assessment.

Description

Genetic locus rs780092 and detection kit for risk assessment of type 2 diabetes

technical field

The invention belongs to the field of biomedicine, and relates to a genetic locus rs780092 and a detection kit for assessing the risk of developing type 2 diabetes.

Background technique

The prevalence of diabetes in my country is showing a rapid upward trend, and it has become another important chronic non-communicable disease that seriously endangers people's health after cardiovascular and cerebrovascular diseases and tumors. The results of a large-scale epidemiological survey published in JAMA, the Journal of the American Medical Association in September 2013 showed that the prevalence of diabetes in people over the age of 18 in my country was 11.6%, which has become the country with the largest number of diabetic patients in the world. Among them, type 2 diabetes accounts for more than 90%. At present, my country has entered a period of high burden of chronic diseases, with the characteristics of "large number of patients, high medical costs, long duration of illness, and large demand for services". The proportion of chronic diseases in the disease burden has reached 70%. Chronic diseases have become a major public health and social problem that affects the improvement of the health of Chinese residents and hinders economic and social development. According to WHO estimates, from 2005 to 2015, the economic loss caused by diabetes and related cardiovascular diseases in China reached 557.7 billion US dollars. Facing the high incidence of chronic diseases, the relevant state departments attach great importance to it, and promote the prevention and treatment of chronic diseases as the focus of health work. Disease risk assessment is one of the important links in the prevention and treatment of chronic diseases. The etiology of type 2 diabetes is complex, which is the result of the joint action of genetic and environmental factors, involving many risk factors.

Blood lipids are considered to be one of the important risk factors for type 2 diabetes, and elevated blood lipids and factors associated with elevated blood lipids are also listed as risk factors for type 2 diabetes, such as elevated triglycerides, elevated total cholesterol, unhealthy diet , lack of exercise, etc. In fact, blood lipids are not only related to environmental factors such as diet and exercise, but also related to individual genetic factors. Studies at home and abroad have found that some genetic loci, mainly single nucleotide polymorphisms (SNPs), are associated with blood lipids. SNP is a change in the DNA sequence caused by a single nucleotide change, resulting in the diversity of the chromosomal genome. SNP has a wide distribution and high density. It has become the third generation of genetic markers after restriction fragment length polymorphism (RFLP) markers and microsatellite (short tandem repeat, STR) markers. It is used in the research of complex diseases such as tumors and diabetes. has an important role.

When assessing the risk of blood lipids for type 2 diabetes, the current focus is on changes in indicators such as triglycerides and cholesterol, while the potential role of blood lipid-related genetic loci is often not taken into account. Specifically, the existing risk assessment methods for type 2 diabetes have the following defects: First, the influence of blood lipid-related genetic loci on the risk of type 2 diabetes is still unclear and has not been included in the risk assessment system. Therefore, the existing risk assessment methods for type 2 diabetes are not comprehensive enough. Second, in the case of the same level of elevated blood lipids, the risk of developing type 2 diabetes varies among individuals due to the different genetic loci carried. Therefore, the existing methods for assessing the risk of type 2 diabetes are not individualized enough. Third, although there are relevant research results abroad, there are obvious differences in the genetic basis and living environment of Chinese and Western populations, and the accuracy of foreign research results in Chinese populations lacks verification by large-scale prospective studies.

Contents of the invention

The object of the present invention is to provide a new application of a substance for detecting the single nucleotide polymorphism of the rs780092 site, and to provide a method for evaluating or assisting evaluation (especially early evaluation or assisting evaluation) to be tested Human risk of type 2 diabetes.

The new application provided by the present invention is specifically: the substance used to detect the single nucleotide polymorphism of the rs780092 site is used in the preparation evaluation or auxiliary evaluation (especially early evaluation or auxiliary evaluation) of the human being suffering from type 2 diabetes risky product applications.

The rs780092 site is located on the human glucokinase regulatory protein gene (GCKR), which is: the 50th nucleoside from the 5' end of the amplified product obtained by PCR amplification using a primer pair using human genomic DNA as a template acid; the nucleotide at the rs780092 site is T or C;

Further, the sequence of the amplified product obtained by PCR amplification using the human genome DNA as a template and the primer pair is sequence 4 in the sequence listing. The 50th nucleotide of sequence 4 is the rs780092 site, which is T or C.

The primer pair is a primer pair composed of the single-stranded DNA shown in sequence 1 in the sequence listing and the single-stranded DNA shown in sequence 2 in the sequence listing.

The substance used to detect the single nucleotide polymorphism at the rs780092 site can specifically be any of the following (1)-(3):

(1) A primer pair consisting of the single-stranded DNA shown in sequence 1 in the sequence listing and the single-stranded DNA shown in sequence 2 in the sequence listing.

(2) A single-stranded DNA set consisting of the single-stranded DNA shown in sequence 1 in the sequence listing, the single-stranded DNA shown in sequence 2 in the sequence listing, and the single-stranded DNA shown in sequence 3 in the sequence listing.

(3) A kit containing the primer pair described in (1) or the set of single-stranded DNA described in (2).

The kit can also contain at least one of the following substances: dNTP, DNA polymerase (such as Taq enzyme), shrimp alkaline phosphatase (SAP). Of course, the kit may also contain PCR amplification buffer and/or the shrimp alkaline phosphatase reaction buffer (SAPbuffer) used in conjunction with the shrimp alkaline phosphatase (SAP), etc.

In addition, the kit may also contain substances for detecting blood lipids. The substance for detecting blood lipid is a reagent and/or instrument for detecting total cholesterol (TC) and/or low-density lipoprotein cholesterol in blood.

The kit may also contain a readable carrier with the following (a) or (b):

(a) the risk of type 2 diabetes is lower for the test persons carrying the T allele at the rs780092 site than for the test persons without the T allele at the rs780092 site;

That is, if the rs780092 locus of the test subject carries the T allele, the risk of the test subject suffering from type 2 diabetes is relatively low; if the rs780092 locus of the test subject does not carry the T allele, Then the risk of the person to be tested suffering from type 2 diabetes is relatively high;

(b) The rs780092 locus is the test person of TT genotype, the risk of developing type 2 diabetes is lower than the rs780092 locus of the TC genotype test person; the rs780092 locus is the TC genotype test person The risk of a person suffering from type 2 diabetes is lower than that of a test person whose rs780092 locus is CC genotype.

The kit may also contain a readable carrier described in (c) or (d):

(c) only considering the impact of the genotyping of the rs780092 locus on the risk of suffering from type 2 diabetes (regardless of the age, sex, BMI, family history of diabetes, smoking, drinking, blood pressure, and blood lipid levels of the tested person on the risk of suffering from type 2 diabetes), each T allele of the rs780092 site can reduce the risk of developing type 2 diabetes by 14%;

(d) not only considering the impact of the blood lipid level of the person to be tested on the risk of suffering from type 2 diabetes, but also considering the impact of the genotype of the rs780092 locus on the risk of suffering from type 2 diabetes (regardless of age, gender, BMI, family history of diabetes, smoking, drinking, blood pressure), at least one of the following (d1)-(d3):

(d1) Analyze total cholesterol and low-density lipoprotein cholesterol as continuous variables, in the test persons whose rs780092 locus is CC genotype, the total cholesterol increases by 1 standard on the basis of 2.39mmol/L Poor (1SD=0.91mmol/L), the risk of the tested person suffering from type 2 diabetes increases by 58% (compared with the people whose rs780092 locus is CC genotype and total cholesterol is less than 2.39mmol/L); low When the density lipoprotein cholesterol increases by 1 standard deviation (1SD=0.66mmol/L) on the basis of 0.49mmol/L, the risk of the test person suffering from type 2 diabetes increases by 43% (the same as the rs780092 site is CC genotype and low-density lipoprotein cholesterol less than 0.49mmol/L);

(d2) Analyze total cholesterol and low-density lipoprotein cholesterol as continuous variables, in the test persons whose rs780092 locus is CT genotype, the total cholesterol increases by 1 standard on the basis of 2.39mmol/L Poor (1SD=0.91mmol/L), the risk of the tested person suffering from type 2 diabetes increases by 28% (compared with the people whose rs780092 locus is CT genotype and total cholesterol is less than 2.39mmol/L); low For every 1 standard deviation (1SD=0.66mmol/L) increase in density lipoprotein cholesterol on the basis of 0.49mmol/L, the risk of the test person suffering from type 2 diabetes increases by 35% (the same as the rs780092 site is CT genotype and low-density lipoprotein cholesterol less than 0.49mmol/L);

(d3) Analyze total cholesterol and low-density lipoprotein cholesterol as continuous variables, in the test persons whose rs780092 locus is TT genotype, the total cholesterol increases by 1 standard on the basis of 2.39mmol/L Poor (1SD=0.91mmol/L), the risk of the test person suffering from type 2 diabetes is only increased by 19% (compared with the people whose rs780092 locus is TT genotype and total cholesterol is less than 2.39mmol/L); Low-density lipoprotein cholesterol increases by 1 standard deviation (1SD=0.66mmol/L) on the basis of 0.49mmol/L, and the risk of the person suffering from type 2 diabetes only increases by 14% (with the rs780092 position Points are compared with people with TT genotype and low-density lipoprotein cholesterol less than 0.49mmol/L).

The above-mentioned substance for detecting the single nucleotide polymorphism of the rs780092 site, and the application of the readable carrier in the preparation of products for evaluating or assisting in evaluating the risk of type 2 diabetes of the tested person Also belong to the protection scope of the present invention.

Of course, the kit may also include conventional components, reagents, etc. for performing SequenomMassARRAY for SNP site genotyping detection.

When performing the test, the genomic DNA of the person to be tested is used as the test sample, and the clinical samples are obtained from a wide range of sources, such as blood, body fluid, tissue cells, etc. Genomic DNA can be prepared by extracting and purifying these clinical samples. When genotyping the rs780092 locus, various existing SNP detection technologies can be used, including but not limited to microarray chip method, Taqman method, mass spectrometry, sequencing method, micro-sequencing, high-resolution melting curve method or a combination of the above methods.

The above-mentioned (1)-(3) are exactly the products claimed in the present invention for evaluating or assisting evaluation (especially early evaluation or assisting evaluation) of the risk of type 2 diabetes of the person to be tested.

In the present invention, the test subject is Chinese.

The present invention clarifies the influence of blood lipid-related genetic locus rs780092 on the risk of type 2 diabetes, and incorporates it into the risk assessment system; according to the blood lipid-related genetic locus rs780092, the influence of elevated blood lipids on the risk of type 2 diabetes of different individuals is evaluated ; In a large prospective cohort, the factors applicable to the risk assessment of type 2 diabetes in the Chinese population were investigated. In addition, the detection method of the present invention is economical and convenient, and is conducive to large-scale popularization among people. The invention has great significance for solving the problems of comprehensiveness, individualization and accuracy of blood lipid and type 2 diabetes risk assessment.

Detailed ways

The experimental methods used in the following examples are conventional methods unless otherwise specified.

The materials and reagents used in the following examples can be obtained from commercial sources unless otherwise specified.

The SNP site is a single nucleotide polymorphism site, and the rs site is a specific SNP site. The rs780092 site is located on the glucokinase regulatory protein gene (GCKR) on chromosome 2 of the human genome (the 50th nucleoside from the 5' end of the amplified product obtained by PCR amplification using human genomic DNA as a template) acid; the nucleotide at the rs780092 site is T or C).

Example 1. Association analysis between the single nucleotide polymorphism of rs780092 site and the risk of developing type 2 diabetes

1. Preparation of detection kits for risk assessment of blood lipids and type 2 diabetes

1. Kit composition

The detection kit for blood lipid and type 2 diabetes risk assessment developed by the inventors of the present invention includes a PCR primer pair for amplifying the gene fragment at the rs780092 site, and a SequenomMassARRAY single-base extension primer for specifically detecting the genotype at the rs780092 site . The sequences of the PCR primer pair are shown as sequence 1 (SEQ ID NO.1) and sequence 2 (SEQ ID NO.2) in the sequence listing. The sequence of the single base extension primer is shown as sequence 3 (SEQ ID NO.3) in the sequence listing.

SEQ ID NO.1: 5'-ACGTTGGATGCCTAGCTCAAAATACCACCC-3';

SEQ ID NO.2: 5'-ACGTTGGATGGGAGGTATAAAGAAGGTGGG-3';

SEQ ID NO. 3: 5'-TTCCATGAGGCCTTCTTT-3'.

The rs780092 site is: the 50th nucleotide from the 5' end of the amplification product obtained by PCR amplification using the PCR primer pair (sequence 1 and sequence 2) using human genomic DNA as a template; The nucleotide at the rs780092 site is T or C. Further, the sequence of the amplified product obtained by PCR amplification using the human genome DNA as a template and the primer pair is sequence 4 in the sequence listing. The 50th nucleotide of sequence 4 is the rs780092 site, which is T or C.

The kit also includes Taq enzyme, SAP (shrimpalkalinephosphatase, shrimp alkaline phosphatase), SAPBuffer, and enzyme-free water.

Said kit can also include conventional components, reagents, etc. for performing SequenomMassARRAY for SNP locus genotyping detection.

2. How to use the kit

The assay method of the present invention is used for assaying genomic DNA derived from human beings. Clinically obtained samples come from a wide range of sources, such as blood, body fluid, tissue cells, etc. Genomic DNA can be prepared by extracting and purifying these samples.

The reagents used in the present invention are all commercially available products, all purchased from Tiangen Biochemical Technology.

Human peripheral blood genomic DNA was prepared using OSR-M102-T1 Blood Genomic DNA Extraction Kit and its matching OSE-M48 Nucleic Acid Extractor (Tiangen Biochemical Technology).

The present invention uses SequenomMassARRAY to detect the genotyping of the rs780092 site. The specific operation is as follows:

(1) Use the primer pair shown in Sequence 1 and Sequence 2 to amplify the target gene fragment. Each reaction volume is 5 μl, including 2 μl Taq enzyme, 1.5 μl enzyme-free water, 0.25 μl each of PCR upstream and downstream primers, and 1 μl DNA sample solution (human peripheral blood genomic DNA, the concentration is 50 ng/μl). Reaction conditions: 94°C for 4min; 94°C for 20s, 56°C for 30s, 72°C for 1min, a total of 45 cycles; 72°C for 5min; 4°C hold.

(2) After the PCR is completed, the PCR product is treated with SAP (shrimpalkalinephosphatase, shrimp alkaline phosphatase) to remove free dNTPs in the system. Prepare alkaline phosphatase treatment reaction solution, SAPMix. Each reaction volume is 2 μl, which includes 1.53 μl enzyme-free water, 0.17 μl SAPBuffer, 0.3 μl SAPEnzyme. Reaction conditions: 37°C for 40 minutes, 85°C for 5 minutes, hold at 4°C, start the PCR instrument for alkaline phosphatase treatment.

(3) Using the single-base extension primer shown in SEQ ID NO:3 to perform single-base extension. Add 2 μl single base extension reaction solution to each of the above reaction systems, and perform the reaction according to the following PCR reaction conditions: I. 94°C for 30s, II. 94°C for 5s, III. 52°C for 5s, IV. 80°C for 5s, V. Continue to III, 4 times, VI. Continue to II, 39 times, VII. 72°C for 3 minutes, VIII. Keep at 4°C.

(4) Spread CleanResin resin on a 6 mg resin plate, add 16 μl of water to the corresponding well of the extension product, pour the dried resin into the extension product plate, seal the film, rotate vertically at a low speed for 30 minutes, and make the resin and The reactants are fully contacted and centrifuged to allow the resin to sink to the bottom of the well.

(5) Start the MassARRAYNanodispenser RS1000 spotting instrument, and move the extension product after resin purification to the 384-well SpectroCHIP (Sequenom) chip.

(6) Analyze the SpectroCHIP chip after spotting using MALDI-TOF (matrix-assisted laser desorption/ionization–timeoffligh, matrix-assisted laser desorption ionization time-of-flight mass spectrometry), and use TYPER4.0 software (Sequenom) to type the detection results and output the results .

2. Use the kit in step 1 to analyze the correlation between the single nucleotide polymorphism at the rs780092 site and the risk of type 2 diabetes

The present invention establishes a large-scale prospective cohort in the Chinese population, and evaluates the influence of the blood lipid-related rs780092 site on the risk of type 2 diabetes through data collection and follow-up. details as follows:

In 2008, 10,185 residents (voluntary) over the age of 40 were recruited in Songnan Town Community, Baoshan District, Shanghai to collect baseline data, including anthropometry (height, weight, waist circumference, BMI, blood pressure, etc.), lifestyle (smoking and alcohol habits, etc.) ) and medical history questionnaires. At the same time, fasting blood samples from each resident were collected for biochemical tests (fasting blood glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol). In this study, a total of 6919 residents provided DNA samples, and the rs780092 locus was genotyped by SequenomMassArray (according to the method in step 1, the rs780092 locus was detected as TT type, TC type or CC type). Among them, 847 samples of patients with type 2 diabetes who were clinically diagnosed (according to the WHO1999 standard) and 69 samples lacking genotyping information of rs780092 locus were excluded. The 5,613 eligible residents in the remaining sample were followed up. The content of the follow-up included questionnaire surveys on lifestyle changes and diabetes history since 2008, anthropometry examinations, and blood biochemical examinations such as fasting blood glucose and blood lipids. According to the WHO 1999 standard, there were 512 new cases of type 2 diabetes since 2008 and up to 2013 follow-up.

(1) Evaluate the risk of type 2 diabetes according to the rs780092 genotyping results (without considering the effects of age, sex, BMI, family history of diabetes, smoking, drinking, blood pressure, and blood lipid levels),

The results showed that each T allele reduces the risk of type 2 diabetes by 14% (OddsRatio[OR]=0.86, 95%ConfidenceInterval[CI]0.75-0.99). The original data are shown in Table 1.

Table 1 Raw data for each T allele reducing the risk of developing type 2 diabetes by 14%

(2) According to the rs780092 genotyping results, the influence of elevated blood lipids on the risk of type 2 diabetes was evaluated (regardless of the effects of gender, age, BMI, family history of diabetes, smoking, drinking, and blood pressure).

The results are shown in Table 2 below:

Table 2 Evaluating the influence of elevated blood lipids on the risk of type 2 diabetes based on rs780092 genotyping results

Total cholesterol and LDL cholesterol were analyzed as continuous variables. In the test persons whose rs780092 genotype is CC, the total cholesterol is on the basis of 2.39mmol/L, every increase of 1 standard deviation (1SD, calculated according to the standard deviation formula, 1SD in the present invention is about 0.91mmol/L) , the risk of type 2 diabetes increased by 58% (compared with CC genotype and total cholesterol less than 2.39mmol/L); 1 standard deviation (1SD, calculated according to the standard deviation formula, 1SD is about 0.66mmol/L in the present invention), the risk of people to be tested suffering from type 2 diabetes increases by 43% (with CC genotype and low-density lipoprotein cholesterol is less than 0.49 mmol/L compared to people).

Total cholesterol and LDL cholesterol were analyzed as continuous variables. In the test persons whose rs780092 genotype is CT, the total cholesterol is on the basis of 2.39mmol/L, for every standard deviation increase (0.91mmol/L), the risk of the test persons suffering from type 2 diabetes increases by 28% ( Compared with people with CT genotype and total cholesterol less than 2.39mmol/L); low-density lipoprotein cholesterol is on the basis of 0.49mmol/L, for every 1 standard deviation (0.66mmol/L) increase, the tested human patient There is a 35% increased risk of type 2 diabetes (compared to people with the CT genotype and LDL cholesterol less than 0.49mmol/L).

Total cholesterol and LDL cholesterol were analyzed as continuous variables. In the test subjects whose rs780092 genotype is TT, on the basis of 2.39mmol/L, the risk of developing type 2 diabetes will only increase by 19% for every 1 standard deviation increase (0.91mmol/L) of total cholesterol (compared with TT genotype and total cholesterol less than 2.39mmol/L); low-density lipoprotein cholesterol on the basis of 0.49mmol/L, for every 1 standard deviation increase (0.66mmol/L), the test person There was only a 14% increased risk of developing type 2 diabetes (compared to people with the TT genotype and LDL cholesterol less than 0.49mmol/L).

Claims (10)

1. The application of the substance used for detecting the single nucleotide polymorphism of the rs780092 site in the preparation of a product for evaluating or assisting in evaluating the risk of type 2 diabetes of a test subject. 2. The application according to claim 1, characterized in that: the rs780092 site is the 50th position from the 5' end of the amplified product obtained by PCR amplification using human genomic DNA as a template Nucleotide; the nucleotide at the rs780092 site is T or C; The primer pair is a primer pair composed of the single-stranded DNA shown in sequence 1 in the sequence listing and the single-stranded DNA shown in sequence 2 in the sequence listing. 3. The application according to claim 1 or 2, characterized in that: the substance for detecting the single nucleotide polymorphism at the rs780092 site is the primer pair according to claim 4 or the primer pair according to claim 5 The complete set of single-stranded DNA or the kit described in any one of claims 6-9. 4. A pair of primers for evaluating or assisting in evaluating the risk of type 2 diabetes in a test subject, consisting of the single-stranded DNA shown in sequence 1 in the sequence listing and the single-stranded DNA shown in sequence 2 in the sequence listing. 5. A set of single-stranded DNA for evaluating or assisting in evaluating the risk of type 2 diabetes of the person to be tested, consisting of the single-stranded DNA shown in sequence 1 in the sequence listing, the single-stranded DNA shown in sequence 2 in the sequence listing and the sequence Composition of single-stranded DNA shown in sequence 3 in the list. 6. A kit for evaluating or assisting in evaluating the risk of type 2 diabetes in a test subject, comprising the primer pair as claimed in claim 4 or the set of single-stranded DNA as claimed in claim 5. 7. The kit according to claim 6, characterized in that: the kit also contains at least one of the following substances: dNTP, DNA polymerase, shrimp alkaline phosphatase; and/or The kit also contains substances for detecting blood lipids; Specifically, the substance for detecting blood lipid is a substance for detecting total cholesterol and/or low-density lipoprotein cholesterol in blood. 8. The kit according to claim 6 or 7, characterized in that: the kit also contains a readable carrier that is described as follows (a) or (b): (a) the risk of type 2 diabetes is lower for the test persons carrying the T allele at the rs780092 site than for the test persons without the T allele at the rs780092 site; (b) The rs780092 locus is the test person of TT genotype, the risk of developing type 2 diabetes is lower than the rs780092 locus of the TC genotype test person; the rs780092 locus is the TC genotype test person The risk of a person suffering from type 2 diabetes is lower than that of a test person whose rs780092 locus is CC genotype. 9. The kit according to any one of claims 6-8, characterized in that: said kit also contains a readable carrier described in (c) or (d): (c) only considering the impact of the genotyping of the rs780092 site on the risk of developing type 2 diabetes, each T allele of the rs780092 site can reduce the risk of developing type 2 diabetes by 14%; (d) Considering both the influence of the blood lipid level of the test subject on the risk of suffering from type 2 diabetes, and the influence of the genotype of the rs780092 locus on the risk of suffering from type 2 diabetes, as follows (d1)- At least one of (d3): (d1) Analyze total cholesterol and low-density lipoprotein cholesterol as continuous variables, in the test persons whose rs780092 locus is CC genotype, the total cholesterol increases by 1 standard on the basis of 2.39mmol/L Poor, the risk of the tested person suffering from type 2 diabetes increased by 58%; the low-density lipoprotein cholesterol increased by 1 standard deviation on the basis of 0.49mmol/L, and the risk of the tested person suffering from type 2 diabetes increased 43%; (d2) Analyze total cholesterol and low-density lipoprotein cholesterol as continuous variables, in the test persons whose rs780092 locus is CT genotype, the total cholesterol increases by 1 standard on the basis of 2.39mmol/L Poor, the risk of the tested person suffering from type 2 diabetes increased by 28%; LDL cholesterol increased by 1 standard deviation on the basis of 0.49mmol/L, the risk of the tested person suffering from type 2 diabetes increased 35%; (d3) Analyze total cholesterol and low-density lipoprotein cholesterol as continuous variables, in the test persons whose rs780092 locus is TT genotype, the total cholesterol increases by 1 standard on the basis of 2.39mmol/L Poor, the risk of the tested person suffering from type 2 diabetes only increases by 19%; low-density lipoprotein cholesterol increases by 1 standard deviation on the basis of 0.49mmol/L, the risk of the tested person suffering from type 2 diabetes Only a 14% increase. 10. The substance for detecting the single nucleotide polymorphism at the rs780092 site described in any one of claims 1-3, and the readable carrier described in claim 8 or 9 in preparation evaluation or auxiliary evaluation Application in products to test the risk of type 2 diabetes in humans.