The possible role of 10398A and 16189C mtDNA variants in providing susceptibility toT2DM in two North Indian populations: a replicative study
The possible role of 10398A and 16189C mtDNA variants in providing susceptibility toT2DM in two North Indian populations: a replicative study
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DOI：
10.1007/s00439-006-0272-4
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发表时间：
2007-01-01
期刊：
影响因子：
5.3
通讯作者：
Bamezai, R. N. K.
中科院分区：
文献类型：
--
作者：
Bhat, Audesh;Koul, Anil;Bamezai, R. N. K.
随着越来越多的研究集中在细胞的这个细胞器上，线粒体在引起疾病中的作用变得越来越明显。这在很大程度上归因于其活性氧（ROS）产生特性。在糖尿病的背景下，ROS被认为触发涉及不同机制的不同形式的胰岛素抵抗。线粒体DNA变异体G10398 A在增加ROS产生和T16189 C变异体引起的氧化应激反应受损中的提示作用值得作为2型糖尿病（T2 DM）的遗传易感因素来解决。对312例T2 DM病例和种族匹配的466例对照进行了病例对照研究，涉及两个北印度人群，称为队列1和队列2（在重复研究中），以测试这种遗传关联。在两个队列中均观察到10398 A等位基因的统计学显著相关性[队列1（OR = 2.67 95%CI 1.77-4.00）;队列2（OR = 1.76 95%CI 1.12-2.77）]。对G10398 A/T16189 C单倍型组合的分析显示，10398 A/16189 C单倍型在两个队列中均提供了风险。总而言之，研究表明10398 A和16189 C等位基因独立或共同导致T2 DM的易感性。
The role of mitochondria in causing diseases is becoming evident as more and more studies are focusing on this organelle of the cell. This is largely attributed to its reactive oxygen species (ROS) production property. In the context of diabetes, ROS is suggested to trigger different forms of insulin resistance involving different mechanisms. The suggestive role of a mtDNA variant G10398A in increasing ROS production and the impaired response to oxidative stress due to T16189C variant is worth addressing as genetic susceptibility factors in type 2 diabetes mellitus (T2DM). A case control study on 312 T2DM cases and ethnically matched 466 controls involving two North Indian populations, referred as cohort 1 and cohort 2 (in a replicative study), was undertaken to test such a genetic association. A statistically significant association was observed for 10398A allele in both the cohorts [cohort1 (OR = 2.67 95% CI 1.77-4.00); cohort2 (OR = 1.76 95%CI 1.12-2.77)]. The analysis of G10398A/T16189C haplotypic combinations revealed that 10398A/16189C haplotype provides a risk in both the cohorts. To sum up the study suggests that 10398A and 16189C alleles provide susceptiblity to T2DM independently as well as together.