KCNQ1基因的常见变异与中国汉族人群的2型糖尿病和空腹血糖受损有关。
Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population.
作者信息
Qi Qibin, Li Huaixing, Loos Ruth J F, Liu Chen, Wu Ying, Hu Frank B, Wu Hongyu, Lu Ling, Yu Zhijie, Lin Xu
机构信息
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China.
出版信息
Hum Mol Genet. 2009 Sep 15;18(18):3508-15. doi: 10.1093/hmg/ddp294. Epub 2009 Jun 25.
Common variants in KCNQ1 have recently been reported to be associated with type 2 diabetes in East Asians. We aimed to examine whether these common variants (rs2074196, rs2237892, rs2237895 and rs2237897) were also associated with type 2 diabetes in a population-based cohort of 3210 Chinese Hans and to explore the underlying mechanisms. The SNPs rs2237892, rs2237895 and rs2237897 were significantly associated with type 2 diabetes (OR: 1.33-1.36, P <or= 0.0009), impaired fasting glucose (IFG) (OR: 1.16-1.19, P <or= 0.0193) and combined IFG/type 2 diabetes (OR: 1.23-1.24, P <or= 0.0004), and the corresponding population attributable risks of type 2 diabetes for the three SNPs were 32.5, 18.8 and 35.8%, respectively. However, rs2074196 showed a weak, but significant association with IFG (OR: 1.18 [1.04-1.33], P = 0.009) and combined IFG/type 2 diabetes (OR: 1.17 [1.05-1.30], P = 0.0053), as well as a trend toward association with type 2 diabetes (OR: 1.15 [0.98-1.35], P = 0.0882), suggesting a different pattern of association when compared with the other three SNPs. The four SNPs were all significantly associated with HOMA-B (P <or= 0.042) while rs2237895 and rs22378897 also showed significant association with fasting glucose (P <or= 0.012). Notably, the associations with type 2 diabetes were markedly attenuated after adjusting for HOMA-B (OR(rs2237892): 1.33 [1.05-1.68], P = 0.018; OR(rs2237895): 1.24 [1.00-1.54], P = 0.0524; OR(rs2237897): 1.22[0.98-1.53], P = 0.09). Moreover, GCCC haplotype showed similar associations with type 2 diabetes (OR: 1.48 [1.17-1.85], P = 0.0008), IFG (OR: 1.32 [1.10-1.57], P = 0.0023), combined IFG/type 2 diabetes (OR: 1.37 [1.17-1.61], P = 8.7 x 10(-5)), and lower HOMA-B values (beta = -4.41 +/- 1.62, P = 0.006). These results suggest that KCNQ1 is a major type 2 diabetes gene in the Chinese Hans and it may confer type 2 diabetes risk by impaired beta-cell function.
最近有报道称，KCNQ1基因的常见变异与东亚人的2型糖尿病有关。我们旨在研究这些常见变异（rs2074196、rs2237892、rs2237895和rs2237897）在3210名中国汉族人群队列中是否也与2型糖尿病相关，并探讨其潜在机制。单核苷酸多态性（SNP）rs2237892、rs2237895和rs2237897与2型糖尿病（比值比：1.33 - 1.36，P≤0.0009）、空腹血糖受损（IFG）（比值比：1.16 - 1.19，P≤0.0193）以及IFG/2型糖尿病合并症（比值比：1.23 - 1.24，P≤0.0004）显著相关，这三个SNP对2型糖尿病的相应人群归因风险分别为32.5%、18.8%和35.8%。然而，rs2074196与IFG（比值比：1.18 [1.04 - 1.33]，P = 0.009）以及IFG/2型糖尿病合并症（比值比：1.17 [1.05 - 1.30]，P = 0.0053）显示出较弱但显著的关联，与2型糖尿病也存在关联趋势（比值比：1.15 [0.98 - 1.35]，P = 0.0882），这表明与其他三个SNP相比，其关联模式有所不同。这四个SNP均与胰岛素抵抗指数（HOMA - B）显著相关（P≤0.042），而rs2237895和rs22378897与空腹血糖也显示出显著关联（P≤0.012）。值得注意的是，在调整HOMA - B后，与2型糖尿病的关联明显减弱（rs2237892的比值比：1.33 [1.05 - 1.68]，P = 0.018；rs2237895的比值比：1.24 [1.00 - 1.54]，P = 0.0524；rs2237897的比值比：1.22[0.98 - 1.53]，P = 0.09）。此外，GCCC单倍型与2型糖尿病（比值比：1.48 [1.17 - 1.85]，P = 0.0008）、IFG（比值比：1.32 [1.10 - 1.57]，P = 0.0023）、IFG/2型糖尿病合并症（比值比：1.37 [1.17 - 1.61]，P = 8.7×10⁻⁵）以及较低的HOMA - B值（β = - 4.41±1.62，P = 0.006）显示出相似的关联。这些结果表明，KCNQ1是中国汉族人群中一个主要的2型糖尿病基因，它可能通过β细胞功能受损导致2型糖尿病风险增加。
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