Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Diabetologia. 2012 Oct;55(10):2655-2659. doi: 10.1007/s00125-012-2636-8. Epub 2012 Jul 13.
AIMS/HYPOTHESIS: There is evidence of overlap between susceptibility loci for type 2 diabetes and obesity. The aim of this study is to explore the association between the established type 2 diabetes locus KCNQ1 and obesity in Han Chinese.
We recruited 6,667 and 6,606 diabetic case-control samples from Shanghai and Hong Kong, respectively. Of the samples, 7.5% and 6.3% were excluded because of genotyping failure or data missing in the association analyses of rs2237892 and rs2237895 with obesity/BMI, respectively.
We found that rs2237892 was associated with lower BMI and lower incidence of overweight/obesity in diabetic patients from Hong Kong (BMI, β = -0.0060 per diabetes risk C allele for log(10)BMI [95% CI -0.0088, -0.0032; p = 2.83 × 10(-5)]; overweight/obesity, OR 0.880 for C allele [95% CI 0.807, 0.960; p = 0.004]) and in the meta-analysis of cases from the two regions (BMI, combined β = -0.0048 per C allele for log(10)BMI [95% CI -0.0070, -0.0026; p = 2.20 × 10(-5)]; overweight/obesity, combined OR 0.890 for C allele [95% CI 0.830, 0.955; p = 0.001]). rs2237895 was also related to decreased BMI (combined β = -0.0042 per diabetes risk C allele for log(10)BMI [95% CI -0.0062, -0.0022; p = 4.30 × 10(-5)]). A significant association with waist circumference was detected for rs2237892 in the pooled analyses (β = -0.0026 per C allele for log(10)[waist circumference] [95% CI -0.0045, -0.0007; p = 0.007]). However, neither an association with the risk of being overweight or obese nor associations with quantitive traits were detected for rs2237892 or rs2237895 in controls.
Our findings indicate that KCNQ1 is associated with obesity in Chinese patients with type 2 diabetes.
目的/假设：2 型糖尿病和肥胖的易感基因座之间存在重叠。本研究旨在探讨在中国汉族人群中已确定的 2 型糖尿病易感基因 KCNQ1 与肥胖之间的关联。
我们分别从上海和香港招募了 6667 名和 6606 名糖尿病病例对照样本。在对 rs2237892 和 rs2237895 与肥胖/体重指数的关联分析中，分别有 7.5%和 6.3%的样本因基因分型失败或数据缺失而被排除在外。
我们发现，rs2237892 与香港糖尿病患者的 BMI 较低和超重/肥胖发生率较低有关（BMI，每增加一个糖尿病风险 C 等位基因，log(10)BMI 减少 0.0060 [95%CI -0.0088, -0.0032;p=2.83×10(-5)]；超重/肥胖，C 等位基因的 OR 为 0.880 [95%CI 0.807, 0.960;p=0.004]），且在两个地区病例的荟萃分析中也存在关联（BMI，每增加一个 C 等位基因，log(10)BMI 减少 0.0048 [95%CI -0.0070, -0.0026;p=2.20×10(-5)]；超重/肥胖，C 等位基因的 OR 为 0.890 [95%CI 0.830, 0.955;p=0.001]）。rs2237895 也与 BMI 降低有关（log(10)BMI 每增加一个糖尿病风险 C 等位基因减少 0.0042 [95%CI -0.0062, -0.0022;p=4.30×10(-5)]）。在合并分析中，rs2237892 与腰围呈显著相关（log(10)[腰围]每增加一个 C 等位基因减少 0.0026 [95%CI -0.0045, -0.0007;p=0.007]）。然而，在对照组中，rs2237892 或 rs2237895 与超重或肥胖的风险或与定量特征均无关联。
我们的研究结果表明，KCNQ1 与中国 2 型糖尿病患者的肥胖有关。
