Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: a study of 3,310 subjects from India and the US.
Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: a study of 3,310 subjects from India and the US.
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DOI：
10.1186/1471-2350-12-18
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发表时间：
2011-01-24
影响因子：
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通讯作者：
Sanghera DK
中科院分区：
文献类型：
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作者：
Been LF;Ralhan S;Wander GS;Mehra NK;Singh J;Mulvihill JJ;Aston CE;Sanghera DK
在日本的全基因组关联研究（GWAS）中，钾电压门控通道KQT样亚家族成员1（KCNQ 1）基因内含子15的多态性与II型糖尿病（T2 D）相关。最近，欧洲GWAS的荟萃分析在KCNQ 1基因的内含子11中检测到与T2 D相关的新的独立信号。本研究的目的是研究这些变异体在来自印度和美国的亚洲印度裔人群中与T2 D的作用。我们研究了来自两个不同队列的3，310名亚洲印度参与者中KCNQ 1基因的四种变体与T2 D和相关数量性状之间的关联，其中包括来自锡克教徒糖尿病研究的旁遮普病例对照队列的2，431名个体和879名居住在美国的亚洲印度移民。我们的数据证实了KCNQ 1基因座（rs 231362）的新信号与T2 D的相关性，在旁遮普队列中显示等位基因比值比（OR）为1.24 95%CI [1.08-1.43]，p = 0.002。在旁遮普（OR 1.14; p = 0.036）和联合队列（荟萃分析OR 1.14; p = 0.018）中也观察到rs 2237895与T2 D中度相关。rs 231362、rs 2237892、rs 2237895的三位点单倍型分析显示GCC单倍型与T2 D相关的证据相当强，显示合并队列中的OR为1.24 95%CI [1.00-1.53]，p = 0.001，排列p = 8 × 10-4。rs 2237895的“C”风险等位基因携带者在美国队列（p = 0.008）以及荟萃分析的联合队列（p = 0.009）中的HOMA-B测量值显著降低。我们的调查已经证实，KCNQ 1基因座内的变异赋予亚洲印度人T2 D的重大风险。单倍型分析进一步表明，与KCNQ 1 SNPs相关的T2 D风险可能来自rs 231362的“G”等位基因和rs 2237895的“C”等位基因，这似乎是通过β细胞功能介导的。
Polymorphisms in intron 15 of potassium voltage-gated channel, KQT-like subfamily member 1 (KCNQ1) gene have been associated with type II diabetes (T2D) in Japanese genome-wide association studies (GWAS). More recently a meta-analysis of European GWAS has detected a new independent signal associated with T2D in intron 11 of the KCNQ1 gene. The purpose of this investigation is to examine the role of these variants with T2D in populations of Asian Indian descent from India and the US. We examined the association between four variants in the KCNQ1 gene with T2D and related quantitative traits in a total of 3,310 Asian Indian participants from two different cohorts comprising 2,431 individuals of the Punjabi case-control cohort from the Sikh Diabetes Study and 879 migrant Asian Indians living in the US. Our data confirmed the association of a new signal at the KCNQ1 locus (rs231362) with T2D showing an allelic odds ratio (OR) of 1.24 95%CI [1.08-1.43], p = 0.002 in the Punjabi cohort. A moderate association with T2D was also seen for rs2237895 in the Punjabi (OR 1.14; p = 0.036) and combined cohorts (meta-analysis OR 1.14; p = 0.018). Three-site haplotype analysis of rs231362, rs2237892, rs2237895 exhibited considerably stronger evidence of association of the GCC haplotype with T2D showing OR of 1.24 95%CI [1.00-1.53], p = 0.001, permutation p = 8 × 10-4 in combined cohorts. The 'C' risk allele carriers of rs2237895 had significantly reduced measures of HOMA-B in the US cohort (p = 0.008) as well as in combined cohort in meta-analysis (p = 0.009). Our investigation has confirmed that the variation within the KCNQ1 locus confers a significant risk to T2D among Asian Indians. Haplotype analysis further suggested that the T2D risk associated with KCNQ1 SNPs may be derived from 'G' allele of rs231362 and 'C' allele of rs2237895 and this appears to be mediated through β cell function.