Association of CDKAL1, CDKN2A/B & HHEX gene polymorphisms with type 2 diabetes mellitus in the population of Hyderabad, India.
Association of CDKAL1, CDKN2A/B & HHEX gene polymorphisms with type 2 diabetes mellitus in the population of Hyderabad, India.
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DOI：
10.4103/0971-5916.184303
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发表时间：
2016-04
期刊：
影响因子：
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通讯作者：
Reddy BM
中科院分区：
文献类型：
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作者：
Kommoju UJ;Samy SK;Maruda J;Irgam K;Kotla JP;Velaga L;Reddy BM
全基因组关联研究（GWAS）显示2型糖尿病（T2 DM）与几个新基因相关。我们在此报告了印度南部海得拉巴人群中三个基因（CDKAL 1、CDKN 2 A/B和HHEX）与2型糖尿病的遗传关联模式。在Sequenom Mass Array平台上对来自印度海得拉巴的1379名个体（758名T2 DM病例和621名对照）的样本进行了CDKAL 1（rs 7754840、rs 7756992）、CDKN 2 A/B（rs 10811661）和HHEX（rs 1111875、rs 7923837）基因的五种单核苷酸多态性（SNP）基因分型。CDKAL 1和CDKN 2 A/B SNP的危险等位基因频率在病例组中相对高于对照组，Logistic回归分析产生了显著的比值比，表明变异等位基因在该人群中具有发生T2 DM的风险。HHEX基因未显示与T2 DM的等位基因或基因型关联。多因素Logistic回归分析显示，CDKAL 1基因多态性与T2 DM的发病有显著相关性，提示该基因在T2 DM的发病中起重要作用。CDKAL 1和CDKN 2 A/B基因的3个SNP与2型糖尿病有显著相关性，而HHEX基因的2个SNP与2型糖尿病无显著相关性。需要进一步的研究，以交叉验证我们的研究结果在一个相对较大的样本。还需要探索HHEX基因的其他SNPs，以明确建立该基因与该人群中T2 DM的关联模式。
The genome-wide association studies (GWAS) have shown an association of type 2 diabetes mellitus (T2DM) with several novel genes. We report here the findings on the pattern of genetic association of three genes (CDKAL1, CDKN2A/B and HHEX) with T2DM in the population of Hyderabad, south India. A sample of 1379 individuals (758 T2DM cases and 621 controls) from Hyderabad, India, were genotyped for five single nucleotide polymorphisms (SNPs) of CDKAL1 (rs7754840, rs7756992) CDKN2A/B (rs10811661) and HHEX (rs1111875, rs7923837) genes on Sequenom Mass Array platform. The risk allele frequencies of the CDKAL1 and CDKN2A/B SNPs were relatively higher in cases than in the controls and the logistic regression analysis yielded significant odds ratios suggesting that the variant alleles conferred risk for developing T2DM in this population. The HHEX gene did not show either allelic or genotypic association with T2DM. The multivariate logistic regression analysis with reference to both alleles and genotypes of CDKAL1 SNPs showed significant association, suggesting an important role for this gene in the T2DM pathophysiology. A significant association was seen of all the three SNPs of CDKAL1 and CDKN2A/B genes with T2DM but none of the two SNPs of HHEX. Further studies are required to cross-validate our findings in a relatively larger sample. It is also necessary to explore other SNPs of HHEX gene to unequivocally establish the pattern of association of this gene with T2DM in this population.