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Gene-gene and gene-environment interactions in the etiology of type 2 diabetes mellitus in the population of Hyderabad, India.

ABSTRACT: 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.

SUBMITTER: Uma Jyothi K

PROVIDER: S-EPMC4443428 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Gene-gene and gene-environment interactions in the etiology of type 2 diabetes mellitus in the population of Hyderabad, India.

Uma Jyothi Kommoju K Reddy Battini Mohan BM

Meta gene 20150521

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 univari ...[more]

PMID: 26042206

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Project description:BACKGROUND We investigated the association between 8 single-nucleotide polymorphisms (SNPs) at 3 genetic loci (CDKAL1, CDKN2A/2B and FTO) with type 2 diabetes (T2D) in a Uyghur population. MATERIAL AND METHODS A case-control study of 879 Uyghur patients with T2D and 895 non-diabetic Uyghur controls was conducted at the Hospital of Xinjiang Medical University between 2010 and 2013. Eight SNPs in CDKAL1, CDKN2A/2B and FTO were analyzed using Sequenom MassARRAY®SNP genotyping. Factors associated with T2D were assessed by logistic regression analyses. Gene-gene and gene-environment interactions were analyzed by generalized multifactor dimensionality reduction. RESULTS Genotype distributions of rs10811661 (CDKN2A/2B), rs7195539, rs8050136, and rs9939609 (FTO) and allele frequencies of rs8050136 and rs9939609 differed significantly between diabetes and control groups (all P<0.05). While rs10811661, rs8050136, and rs9939609 were eliminated after adjusting for covariates (P>0.05), rs7195539 distribution differed significantly in co-dominant and dominant models (P<0.05). In gene-gene interaction analysis, after adjusting for covariates the two-locus rs10811661-rs7195539 interaction model had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.5483 (P=0.014). In gene-environment interaction analysis, the 3-locus interaction model TG-HDL-family history of diabetes had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.7072 (P<0.001). The 4-locus interaction model, rs7195539-TG-HDL-family history of diabetes had a cross-validation consistency of 8/10 (P<0.001). CONCLUSIONS Polymorphisms in CDKN2A/2B and FTO, but not CDKAL1, may be associated with T2D, and alleles rs8050136 and rs9939609 are likely risk alleles for T2D in this population. There were potential interactions among CDKN2A/2B (rs10811661) - FTO (rs7195539) or FTO (rs7195539)-TG-HDL-family history of diabetes in the pathogenesis of T2D in a Uyghur population.

Dataset Information

Gene-gene and gene-environment interactions in the etiology of type 2 diabetes mellitus in the population of Hyderabad, India.

Publications

Gene-gene and gene-environment interactions in the etiology of type 2 diabetes mellitus in the population of Hyderabad, India.

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