The Study Of Early Screening Of Type2Diabetes In Chinese Han Population

Type2diabetes (T2D) is a common but and complex disease. With a prevalence, it isboth high and increasing. Diabetes has become a major public health problem around theworld, including China. At present the glycated hemoglobin, fasting blood sugar and sugartolerance corresponding indicators mainly clinical diagnosis of T2D, were diagnosed by theglycated hemoglobin, fasting blood sugar and sugar tolerance, but this diagnostic standardsare not involved in the essential reason of the disease, so most of the patients have not beenfound as at early as possiblestage. Given the heritability of T2D, it is very important to theidentificatione the of novel susceptibility genes has been the subject of significant research.The ability to identify SNPs that confer risk of common diseases is an invaluable tools for todevelopinge clinic screening meaningful tests for screening, as well as improved preventionand early intervention. We have selected11SNPs were selected to be investigated based onfrom previous reports, which aim to develop a genetic susceptibility model for T2D in theChinese popμlation.Methods1. A total of362individuals, including222patients with T2D and140control subjects,were included in the present study. All participants were unrelated and samples werecollected between May2011and April2012from Ningbo Lihuili Hospital, China. We testedthe clinical features of the participants, which include body height, bodyweight, bloodpressure, fasting blood glucose (FPG), total cholesterol (CHOL), high density lipoproteincholesterol (HDL), low density lipoprotein cholesterol (LDL) and triglyceride (TG).2. Eleven SNPs identified in recent GWAS or large candidate gene studies wereselected for analysis. 3. Genomic DNA was isolated from specimens using a Whole Blood DNA ExtractionKit according to the manufacturer’s instructions. To assess genetic loci, primer pairs weredesigned based on the published SNP sequences, using a PCR Master Mix. the polymerasechain reaction products were sequenced and analyzed.4. Statistical Analysis： Quantitative data with normal distribution variables wereanalyzed by One-way ANOVA test. The Hardy-Weinberg Equilibrium (HWE) test wasperformed to assess the individual polymorphism in the control groups. Logistic regressionanalysis was used to measure the crude odds ratios (ORs) and adjusted ORs by age, sex, andBMI variables. The resμlts included the addictive, recessive and dominant models. The ORswith95%confidence intervals (CIs) are shown.5. Genetic association studies on T2D and rs2237892in the KCNQ1gene, rs7756992in the CDKAL1gene and rs10811661in the CDKN2B gene were systematically reviewed.6. Stata software11.0was used to evaluate the heterogeneity between case and control,Egger’s regression test was conducted to identify publication bias, Heterogeneity acrossindividual studies was calculated using the Dersimonian and Laird Q test.Results：1. Triglycerides, total cholesterol, high density lipoprotein, and body mass index weresignificantly higher among cases than controls. P <0.05.2. After the primer pairs were designed, we finished genotyping eleven SNPs whichinclude rs5219， rs1801282， rs7903146， rs4402960， rs7756992， rs13266634，rs1111875， rs4430796， rs2237892， rs10010131， rs10811661.3. Consistency of the genotype frequencies with Hardy–Weinberg equilibrium (HWE)was analyzed by the Arlequin program, rs13266634and rs7903146were not in HWE（P <0.001）, Other tested SNP were in HWE.4. Trend analysis of genotypes distribution between case and control group revealedrs2237892in the KCNQ1gene, rs7756992in the CDKAL1gene and rs10811661in theCDKN2B gene were associated with T2D (P <0.05). After adjusting theconfounders of age, gender and BMI, the above results remain significant andthe association between T2D and rs5219also discovered. No significant differences was found between the case and control groups of rs1801282, rs4402960, rs1111875andrs4430786(P>0.05）.5. The risk C allele of rs2237892, risk G allele of7756992and risk Tallele ofrs10811661were significantly associated with T2D（rs2237892OR (95%CI):1.45(1-2.08)， rs7756992OR (95%CI):1.6(1.19-2.17)， rs10811661OR (95%CI):1.32(0.98-1.79)）。6. This study collected papers include:14papers about the association of KCNQ1(rs2237892site) gene polymorphism with type2diabetes, included20562cases of T2D and18565controls;8papers about the association of CDKAL1(rs7756992site) genepolymorphism with type2diabetes, included14512cases of T2D and16280controls;8papers about the association of CDKN2B (rs10811661site) gene polymorphism with type2diabetes, included10291cases of T2D and11309controls.7. There is no visual publication bias in the funnel plot with the SNP, Significantheterogeneity was present among the data sets, rs2237892C allele appeared to be one of thegenetic risk factors for susceptibility to type2diabetes; rs7756992G allele appeared to beone of the genetic risk factors for susceptibility to type2diabetes; rs108116611T alleleappeared to be one of the genetic risk factors for susceptibility to type2diabetes.ConclusionsFirst, rs2237892in the KCNQ1gene, rs7756992in the CDKAL1gene andrs10811661in the CDKN2B gene were associated with T2D.Second, the risk C allele ofrs2237892, risk G allele of7756992and risk Tallele of rs10811661were significantlyassociated with T2D, Finally, rs2237892, rs7756992and rs10811661can be used aspredictive biomarkers in Chinese.