Association ofIRS1,CAPN10, andPPARGgene polymorphisms with type 2 diabetes mellitus in the high-risk population of Hyderabad, India 在印度海得拉巴高风险人群中IRS1、CAPN10以及PPARG基因多态性与2型糖尿病的关系

Background We attempted to validate earlier findings on the nature of the association of the IRS1, CAPN10, and PPARG genes with type 2 diabetes mellitus (T2DM) in the high-risk population of Hyderabad, India. Methods A sample of 1379 subjects (758 T2DM patients, 621 controls) was genotyped for single nucleotide polymorphisms (SNPs) of the IRS1 (rs1801278), CAPN10 (rs3792267, rs5030952), and PPARG (rs1801282) genes. Results The allele and genotype frequencies of IRS1 (rs1801278) and CAPN10 (rs3792267) SNPs differed significantly between the patient and control groups. Logistic regression analysis suggested a significant association of these two SNPs (P ≤ 0.007) with T2DM and the strength of association did not alter when adjusted for age, gender, body mass index, and the waist : hip ratio as covariates. The same two SNPs showed significant association in multivariate logistic regression analyses, even after Bonferroni correction for multiple testing, suggesting an independent nature of the role of these genes in the manifestation of T2DM in our population. Conclusions We replicated the significant association of rs1801278 and rs3792267 SNPs of the IRS1 and CAPN10 genes with T2DM in the population of Hyderabad. Despite the known biological significance of the PPARG gene and a sufficient statistical power of the present study, we could not replicate the association of PPARG with T2DM in our high-risk population. Given the vast ethnic, geographic, and genetic heterogeneity of the Indian population, many more studies are needed covering the ethnic and geographic heterogeneity of India to enable identification of an Indian-specific profile of genes associated with T2DM. 摘要 背景：我们的目的是在印度海得拉巴高风险人群中验证早先就发现了的IRS1、CAPN10以及PPARG基因多态性与2型糖尿病之间的本质关系。 方法：对1379名受试者（758名2型糖尿病患者，621名对照者）的样本进行了基因分型，分析了IRS1（rs1801278）、CAPN10（rs3792267, rs5030952）以及PPARG（rs1801282）基因的单核苷酸多态性（single nucleotide polymorphisms，SNPs）。 结果：IRS1（rs1801278）与CAPN10（rs3792267）SNPs的等位基因以及基因型的出现频率在糖尿病患者与对照组之间存在显著差异。对数回归分析结果显示这两种SNPs与2型糖尿病显著相关（P ≤ 0.007），并且相关强度经过年龄、性别、体重指数以及腰臀比这些协变量的校正后仍然没有变化。在多因素对数回归分析中这两种SNPs同样显示有显著相关性，即使经过Bonferroni多重检验校正后仍然如此，这提示我们人群中的这些基因对2型糖尿病的表现具有独立的影响。 结论：我们在海得拉巴人群中再次证实了IRS1与CAPN10基因中的rs1801278与rs3792267 SNPs与2型糖尿病之间具有显著相关性。尽管目前我们已知PPARG基因与2型糖尿病之间具有显著的生物学相关性，并且当前这项研究也具有足够的统计学效力，但是在我们的这个高危人群中我们并不能够再次证实PPARG与2型糖尿病之间的关系。由于印度人群的多种族，宽广的地域以及遗传的异质性，因此需要有更多覆盖印度种族与地域异质性的研究来鉴别印度特有的T2DM相关基因。