| ObjectivesThe study was to investigate the asssociation between four polymorphism locis of poyassium voltage-gated channel,and KQT-like subfamily member 1(KCNQ1)and type 2 diabetes mellitus(T2DM)susceptibility.Moreover,the gene-environment interaction on the susceptibility of T2 DM was evaluated.MethodsA total of 522 subjects with T2 DM were selected in the current study and the control was matched by age and gender according to a 1:1 case-control study design.The participants were from the the Henan Rural Cohort Study(Registration number: ChiCTR-OOC-15006699).The genotyp of SNP was mainly achieved by SNPscanTM Kit.The distribution differences between the case and control group were compared through the paired t test and the paired chi square.The conditional logistic regression model was used to explore the associations between the susceptibility of T2 DM and rs163182 loci,rs2237892 loci,rs2283228 loci and rs2299620 loci in the KCNQ1 gene.The genetic risk score(GRS)model was constructed to evaluate their effects on the ratio of T2 DM.The haplo stats package in R software was used to test the association between haplotype and the susceptibility of T2 DM.The interaction between gene and environment for T2 DM was analysed by the multifactor dimensionality reduction(MDR)software.The addition and multiply interactions between KCNQ1 gene rs2299620 loci and body mass index(BMI)was analyzed.Results1.The analyses of basic characteristic showed that marital status,education,smoking,drinking,BMI,waist circumference,waist to hip ratio,waist to height ratio,blood pressure index,physical activity and fasting plasma glucose concentration distribution were statistically different in the two groups(P<0.05).2.The results of gene polymorphisms indicated that the TT genotype of rs2299620 loci was negatively associatied with T2 DM compared to CC genotype,and the odds ratio(OR)and confidence interval(CI)was 0.578(0.358,0.931)in the adjusted model.The OR of T allele in rs2299620 loci for T2 DM was 0.761(0.626,0.926).The OR of TT genotype of rs2237892 loci for T2 DM was 0.807(0.606,1.073).The T allele of rs2237892 loci was negatively related with T2DM(OR: 0.772,95% CI: 0.632-0.943).The OR of C allele in rs163182 loci for T2 DM was 0.974(0.806,1.178).The OR of C allele in rs2283228 loci for T2 DM was 0.899(0.742,1.088).3.The study found that GTCT haplotypes reduced the susceptibility of T2 DM compared with GCAC haplotypes after adjusting for the covariates,and the corresponding OR and 95%CI value was 0.695(0.546,0.884)in the haplotypes analysis.The associations between T2 DM and CCAC,CCAT,CCCC,GCCC,GCCT,GTAC and GTCC haplotypes were not found.4.The GRS results showed that the OR for T2 DM was 0.878(0.768,1.004)with the value of simple GRS increased.In the weighted GRS and the weighted GRS based on the Minor Allele Frequency(MAF),the Q4 group of both have lower risk of T2 DM,and the corresponding ORs(95% CIs)were 0.567(0.356,0.903)and 0.561(0.352,0.893),respectively.With the increasement of GRS,the ORs(95% CIs)of weighted GRS and weighted GRS based on MAF for T2 DM were 0.867(0.757,0.994)and 0.857(0.751,0.979),respectively.5.The results of the genetic environment interaction analysis indicate that the optimal model was rs2299620 loci and BMI.The rs2299620 loci and BMI had negative additive interaction,and the interaction index was 0.431(0.190,0.672),and the relative excess risk was-1.220(-2.348,-0.092),and the interaction attribution ratio was-0.634(-1.184,-0.084).The multiply effect was negative associated with T2DM(OR: 0.611,95%CI: 0.384-0.972).Conclusions1.The TT genotype of rs2299620 loci was negatively associated with T2 DM,and the T allele of rs2237892 loci and rs2299620 loci could reduce the risk of T2 DM.2.The GTCT haplotype,the highest group of weighted GRS and weighted GRS based on MAF could reduce the susceptibility of T2 DM.3.There were multiply effect and negative additive interaction between KCNQ1 gene rs2299620 loci and BMI in the risk of T2 DM. |
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