Gene-gene and gene-environment interactions in the etiology of type 2 diabetes mellitus in the population of Hyderabad, India.
Gene-gene and gene-environment interactions in the etiology of type 2 diabetes mellitus in the population of Hyderabad, India.
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DOI：
10.1016/j.mgene.2015.05.001
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发表时间：
2015-09
期刊：
影响因子：
0.7
通讯作者：
Reddy, Battini Mohan
中科院分区：
文献类型：
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作者：
Uma Jyothi, Kommoju;Reddy, Battini Mohan
使用Sequenom Massarray平台，对来自印度海得拉巴市的1379名个体，758名T2 DM患者和621名对照进行了来自9个不同基因的15个SNP的基因分型。这些数据进行了分析，以研究基因-基因和基因-环境相互作用在T2 DM的表现中的作用。多因素分析显示TCF 7 L2、CDKAL 1、IGF 2BP 2、HHEX和PPARG基因与T2 DM显著相关，而单因素分析仅显示前两个基因与T2 DM相关。TCF 7 L2、CAPN 10和CDKAL 1基因也观察到显著的基因-基因和基因-环境相互作用，突出了它们在T2 DM病理生理学中的重要性。在对风险等位基因的累积效应的分析中，SLC 30 A8由于其存在于风险等位基因的所有组合中而作为疾病的显著贡献者介入。风险等位基因类别1-4和5-6之间的显著差异分别在显示保护作用和易感作用方面是明显的，而后者的特征在于存在TCF 7 L2和CDKAL 1变体。总体而言，这两个基因TCF 7 L2和CDKAL 1显示出与T2 DM的强关联，无论是单独还是与其他基因的相互作用。然而，我们需要进一步研究基因-基因和基因-环境之间的相互作用异质性的印度人口，以获得明确的结论，适用于印度人口作为一个整体。基因-基因和基因-环境相互作用与T2 DM作用的证据表明，TCF 7 L2和CDKAL 1是该人群中突出的T2 DM易感基因。有助于了解T2 DM病因学中的相互作用
Fifteen SNPs from nine different genes were genotyped on 1379 individuals, 758 T2DM patients and 621 controls, from the city of Hyderabad, India, using Sequenom Massarray platform. These data were analyzed to examine the role of gene–gene and gene–environment interactions in the manifestation of T2DM. The multivariate analysis suggests that TCF7L2, CDKAL1, IGF2BP2, HHEX and PPARG genes are significantly associated with T2DM, albeit only the first two of the above 5 were associated in the univariate analysis. Significant gene–gene and gene–environment interactions were also observed with reference to TCF7L2, CAPN10 and CDKAL1 genes, highlighting their importance in the pathophysiology of T2DM. In the analysis for cumulative effect of risk alleles, SLC30A8 steps in as significant contributor to the disease by its presence in all combinations of risk alleles. A striking difference between risk allele categories, 1–4 and 5–6, was evident in showing protective and susceptible roles, respectively, while the latter was characterized by the presence of TCF7L2 and CDKAL1 variants. Overall, these two genes TCF7L2 and CDKAL1 showed strong association with T2DM, either individually or in interaction with the other genes. However, we need further studies on gene–gene and gene–environment interactions among heterogeneous Indian populations to obtain unequivocal conclusions that are applicable for the Indian population as a whole. Evidence for the role of gene-gene and gene–environment interactions with T2DM TCF7L2 and CDKAL1 emerged as prominent T2DM susceptible genes in this population. Contributes to the knowledge of understanding the interactions in the etiology of T2DM