Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore.
Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore.
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作者：
Tan JT;Nurbaya S;Gardner D;Ye S;Tai ES;Ng DP
通过全基因组关联研究发现，钾电压门控通道、KQT 样亚家族成员 1 (KCNQ1) 是东亚和欧洲人群对 2 型糖尿病易感性的有力候选者。我们的目的是描述居住在新加坡的华人、马来人和亚裔印度人样本中 KCNQ1 基因座的多态性与胰岛素抵抗、β 细胞功能和其他 2 型糖尿病相关特征之间的关联。我们对 1998 年新加坡国家健康调查队列中 3,734 名参与者（2,520 名中国人、693 名马来人和 521 名亚洲印度人）的 3,734 名参与者检查了之前报道的 4 个 KCNQ1 单核苷酸多态性 (SNP) 与 2 型糖尿病相关特征之间的关联。使用稳态模型评估方法根据空腹胰岛素和血糖计算胰岛素抵抗，而使用 120 分钟校正的胰岛素反应 (CIR120) 评估胰腺 β 细胞功能。 SNP rs2237897、rs2237892 和 rs2283228 与 2 型糖尿病显着相关（比值比 [OR] 1.48，P = 3 × 10−4；OR 1.38，P = 0.002；OR 1.31，P = 0.012）。在中国人群中，rs2237897、rs2237892和rs2283228的风险等位基因与较高的空腹血糖水平（分别P=0.014、0.011和0.034）和降低的CIR120（分别P=0.007、0.013和0.014）显着相关。在马来人和亚裔印度少数群体中也观察到了类似的趋势，尽管由于样本量有限，这一趋势并未达到统计显着性。与 KCNQ1 相关的 2 型糖尿病风险增加可能是由胰岛素分泌减少引起的。进一步的研究将有助于复制这些发现并充分描述 KCNQ1 及其相关通路在疾病发病机制中的作用。
The potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) has been found through a genome-wide association study to be a strong candidate for conferring susceptibility to type 2 diabetes in East Asian and European populations. Our objective was to describe the association between polymorphisms at the KCNQ1 locus with insulin resistance, β-cell function, and other type 2 diabetes–related traits in a sample of Chinese, Malays, and Asian Indians living in Singapore. We examined the associations between four previously reported KCNQ1 single-nucleotide polymorphisms (SNPs) with type 2 diabetes–related traits in 3,734 participants from the population-based 1998 Singapore National Health Survey cohort (2,520 Chinese, 693 Malay, and 521 Asian Indians). Insulin resistance was calculated from fasting insulin and glucose using the homeostasis model assessment method, whereas pancreatic β-cell function was assessed using the corrected insulin response at 120 min (CIR120). SNPs rs2237897, rs2237892, and rs2283228 were significantly associated with type 2 diabetes (odds ratio [OR] 1.48, P = 3 × 10−4; OR 1.38, P = 0.002; OR 1.31, P = 0.012, respectively). Within the Chinese population, the risk alleles for rs2237897, rs2237892, and rs2283228 were significantly associated with higher fasting glucose levels (P = 0.014, 0.011, and 0.034, respectively) and reduced CIR120(P = 0.007, 0.013, and 0.014, respectively). A similar trend was observed among the Malay and Asian Indian minority groups, although this did not reach statistical significance because of limited sample sizes. The increased risk for type 2 diabetes associated with KCNQ1 is likely to be caused by a reduction in insulin secretion. Further studies will be useful to replicate these findings and to fully delineate the role of KCNQ1 and its related pathways in disease pathogenesis.
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影响因子：
7.7
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