South Asia Network for Chronic Disease, Public Health Foundation of India, C-1/52, Safdarjung Development Area, New Delhi 110016, India.
Diabetologia. 2012 Feb;55(2):349-57. doi: 10.1007/s00125-011-2355-6. Epub 2011 Nov 4.
AIMS/HYPOTHESIS: Evaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell function (HOMA-β), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population.
We genotyped 3,089 sib pairs recruited in the Indian Migration Study from four cities in India (Lucknow, Nagpur, Hyderabad and Bangalore) for 31 SNPs in 24 genes previously associated with type 2 diabetes in European populations. We conducted within-sib-pair analysis for type 2 diabetes and its related quantitative traits.
The risk-allele frequencies of all the SNPs were comparable with those reported in western populations. We demonstrated significant associations of CXCR4 (rs932206), CDKAL1 (rs7756992) and TCF7L2 (rs7903146, rs12255372) with fasting glucose, with β values of 0.007 (p = 0.05), 0.01 (p = 0.01), 0.007 (p = 0.05), 0.01 (p = 0.003) and 0.08 (p = 0.01), respectively. Variants in NOTCH2 (rs10923931), TCF-2 (also known as HNF1B) (rs757210), ADAM30 (rs2641348) and CDKN2A/B (rs10811661) significantly predicted fasting insulin, with β values of -0.06 (p = 0.04), 0.05 (p = 0.05), -0.08 (p = 0.01) and -0.08 (p = 0.02), respectively. For HOMA-IR, we detected associations with TCF-2, ADAM30 and CDKN2A/B, with β values of 0.05 (p = 0.04), -0.07 (p = 0.03) and -0.08 (p = 0.02), respectively. We also found significant associations of ADAM30 (β = -0.05; p = 0.01) and CDKN2A/B (β = -0.05; p = 0.03) with HOMA-β. THADA variant (rs7578597) was associated with type 2 diabetes (OR 1.5; 95% CI 1.04, 2.22; p = 0.03).
CONCLUSIONS/INTERPRETATION: We validated the association of seven established loci with intermediate traits related to type 2 diabetes in an Indian population using a design resistant to population stratification.
目的/假设：评估 31 个常见的单核苷酸多态性（SNP）与空腹血糖、空腹胰岛素、HOMA-β 细胞功能（HOMA-β）、HOMA-胰岛素抵抗（HOMA-IR）和 2 型糖尿病在印度人群中的关联。
我们对来自印度四个城市（勒克瑙、那格浦尔、海德拉巴和班加罗尔）的印度移民研究中的 3089 对同胞进行了 24 个基因中 31 个与欧洲人群 2 型糖尿病相关的 SNP 的基因分型。我们对 2 型糖尿病及其相关定量特征进行了同胞内分析。
所有 SNP 的风险等位基因频率与西方人群报道的相似。我们证明了 CXCR4（rs932206）、CDKAL1（rs7756992）和 TCF7L2（rs7903146、rs12255372）与空腹血糖显著相关，β 值分别为 0.007（p=0.05）、0.01（p=0.01）、0.007（p=0.05）、0.01（p=0.003）和 0.08（p=0.01）。NOTCH2（rs10923931）、TCF-2（也称为 HNF1B）（rs757210）、ADAM30（rs2641348）和 CDKN2A/B（rs10811661）中的变体显著预测空腹胰岛素，β 值分别为-0.06（p=0.04）、0.05（p=0.05）、-0.08（p=0.01）和-0.08（p=0.02）。对于 HOMA-IR，我们检测到 TCF-2、ADAM30 和 CDKN2A/B 与 HOMA-IR 相关，β 值分别为 0.05（p=0.04）、-0.07（p=0.03）和-0.08（p=0.02）。我们还发现 ADAM30（β=-0.05；p=0.01）和 CDKN2A/B（β=-0.05；p=0.03）与 HOMA-β 显著相关。THADA 变体（rs7578597）与 2 型糖尿病相关（OR 1.5；95%CI 1.04，2.22；p=0.03）。
结论/解释：我们使用一种抗人群分层的设计，验证了七个已建立的位点与印度人群中 2 型糖尿病相关的中间特征的关联。
