TOMM7遗传变异及基因-环境交互作用与我国侗族人群2型糖尿病的关联研究

Association of genetic variants in TOMM7 gene and geneenvironment interaction with type 2 diabetes in Chinese Dong population

目的:探讨全基因组关联研究(genome-wide association studies,GWAS)中识别的7个遗传位点与我国侗族人群2型糖尿病(type 2 diabetes mellitus,T2DM)的相关性。方法:在我国侗族人群中采用病例对照研究方法,利用多重PCR-SNa Pshot法对PARD3B(rs849230),LOC729993(rs149228),EPHA4(rs16862811),HNT(rs3099797),PTPRD(rs17584499与rs649891),TOMM7(rs2240727)6个基因的7个位点进行基因分型。采用非条件二分类logistic回归方法分析每个多态位点与T2DM的相关性,利用边缘结构线性优势比模型进行基因与环境因素的交互作用分析。结果:本研究共包括209例T2DM患者与209例健康对照。TOMM7基因的rs2240727位点多态性与T2DM相关(对于每个拷贝的风险等位基因T,OR=1.50,P=0.004),且CT和TT基因型是T2DM的风险基因型,OR分别为2.07(95%CI:1.14~3.76)和2.75(95%CI:1.46~5.17),经Bonferroni多重比较校正后,上述结果仍然有意义(均P<0.05)。经调整年龄、性别、体质量指数(body mass index,BMI)后,rs2240727位点与T2DM仍有相关性(P<0.01)。交互作用分析结果表明:rs2240727位点与BMI、腰臀比(waist-hip ratio,WHR)、高血压、糖尿病家族史之间存在正交互作用,调整性别、年龄后,交互作用超额相对危险度(relative excess risk of interaction,RERI)分别为1.5430(95%CI:0.5797~2.5062),2.6520(95%CI:1.7516~3.5524),2.9131(95%CI:1.7959~4.0303),4.2062(95%CI:1.1686~8.2439),差异有统计学意义(均P<0.05)。结论:TOMM7基因的rs2240727位点遗传变异与我国侗族人群的T2DM相关,且与BMI、WHR、高血压和糖尿病家族史之间存在正交互作用。

Objective: To investigate the association of 7 novel genetic loci identified in a recent genome-wide association studies(GWAS) with T2 DM in Chinese Dong populations.Methods: A case-controlled study was performed in individuals of Chinese Dong nationality. The genotypes of PARD3B(rs849230), LOC729993(rs149228), EPHA4(rs16862811), HNT(rs3099797), PTPRD(rs17584499 and rs649891), TOMM7(rs2240727) genes were determined by Multiplex PCR-SNa Pshot. The independent association between each polymorphism and T2 DM was assessed by unconditional binary logistic regression analysis. The gene-environment interaction was assessed by marginal structural linear odds model. Results: A total of 209 cases of T2 DM and 209 control subjects were enrolled in the study. The polymorphism of rs2240727 in TOMM7 gene was associated with T2DM(OR=1.50, per copy of the risk T allele, P=0.004). In addition, CT(OR=2.07, 95% CI: 1.14-3.76) and TT(OR=2.75, 95% CI: 1.46-5.17) were risk genotypes for T2 DM. After the correction for multiple test, the association remained significant(all P<0.05). After adjustment for the confounders of age, gender, and BMI, the association remained significant(P<0.05). The results of interaction analysis indicated that there were interaction between rs2240727 locus and BMI, WHR, hypertension and family history of diabetes. After adjustment for age and gender, the results of relative excess risk of interaction(RERI) were 1.5430(95% CI: 0.5797-2.5062), 2.6520(95% CI: 1.7516-3.5524), 2.9131(95% CI: 1.7959-4.0303), 4.2062(95% CI: 1.1686-8.2439), respectively(all P<0.05).Conclusion: The rs2240727 genetic variant in TOMM7 is associated with T2 DM in Chinese Dong population. There is positive interaction between rs2240727 and BMI, WHR, hypertension as well as family history of diabetes.