PGC-1α Thr394Thr and Gly482Ser variants are significantly associated with T2DM in two North Indian populations:: a replicate case-control study
PGC-1α Thr394Thr and Gly482Ser variants are significantly associated with T2DM in two North Indian populations:: a replicate case-control study
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DOI：
10.1007/s00439-007-0352-0
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发表时间：
2007-06-01
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.
最近的观察表明，过氧化物酶体增殖物激活受体γ辅激活因子1 α（PGC 1A）负责诱导活性氧（ROS）解毒剂，ROS触发胰岛素抵抗，支持该基因可能在2型糖尿病（T2 DM）发病中发挥的作用。在来自两个北印度人群（代表第1组（克什米尔人群）和第2组（旁遮普和查谟人群））的822例受试者（351例T2 DM病例和471例对照）中对两种PGC 1A变体Thr 394 Thr（rs 2970847）和Gly 482 Ser（rs 8192673）进行基因分型。在应用Bonferroni校正后，第1组和第2组均显示Thr 394 Thr变异与T2 DM显著相关（分别为P = 0.001和0.012）。对Thr 394 Thr易感基因型（rs 2970847 G/A和A/A）进行Logistic回归分析，结果显示第1组T2 DM风险增加1.89-（95%CI 1.25-2.85）倍，第2组增加1.81-（95%CI 1.19-2.78）倍。第1组中易感基因Ser 482（rs 8192673 G/A和A/A）基因型的T2 DM风险高2.04倍（95%CI 1.47-3.03）。当与PGC 1A变体联合研究时，观察到的与T2 DM相关的线粒体基因型背景（Bhat et al. 2007）显示，在PGC 1A的两个多态性基因座处，具有mt 10398 G和16189 T沿着G/G基因型背景的对照组中患病率增加。这些观察结果表明，两种基因型背景一起可以提供针对T2 DM的保护。
The recent observations that Peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1A) is responsible for the induction of reactive oxygen species (ROS) detoxifying agents and that ROS triggers insulin resistance, support the role that this gene could play in the onset of Type 2 diabetes mellitus (T2DM). Two PGC1A variants Thr394Thr (rs2970847) and Gly482Ser (rs8192673) were genotyped in 822 subjects (351 T2DM cases and 471 controls) from two North Indian populations, represented as Group 1 (Kashmir population) and Group 2 (Punjab and Jammu population). Both Groups 1 and 2 showed a significant association of Thr394Thr variant with T2DM after applying Bonferroni corrections (P = 0.001 and 0.012, respectively). Logistic regression analysis for Thr394Thr susceptible genotypes together (rs2970847 G/A and A/A) conferred a 1.89-(95%CI 1.25-2.85) fold higher risk for T2DM in Group 1 and 1.81-(95%CI 1.19-2.78) fold risk in Group 2. The susceptible, Ser482 (rs8192673 G/A and A/A) genotypes, gave a 2.04 (95%CI 1.47-3.03) fold higher risk for T2DM in Group 1. Mitochondrial genotype backgrounds observed in association with T2DM (Bhat et al. 2007), when studied in combination with PGC1A variants, showed an increased prevalence in controls with mt10398G and 16189T along with G/G genotype background at the two polymorphic loci of PGC1A. These observations suggest that the two genotype backgrounds together could provide protection against T2DM.