Qin L J, Lv Y, Huang Q Y
College of Life Sciences, Central China Normal University, Wuhan, Hubei, China.
Genet Mol Res. 2013 Aug 20;12(3):2990-3002. doi: 10.4238/2013.August.20.1.
KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11) and ABCC8 (ATP-binding cassette, subfamily C (CFTR/MRP), member 8) have been studied for association with type 2 diabetes in various ethnic populations with contradictory results. We performed a comprehensive meta-analysis for KCNJ11 rs5219, rs5210, rs5215, and ABCC8 rs757110 to evaluate the effect of these regions on genetic susceptibility for type 2 diabetes. Forty-one case-control association studies of KCNJ11 and ABCC8 polymorphisms with type 2 diabetes, including 61,879 subjects, were identified and used in our meta-analysis. Combined odds ratios (OR) of associations of this disease with the rs5219 T, rs5210 G, rs5215 G, and rs757110 G alleles were 1.15 [95% confidence interval (95%CI) = 1.10-1.21, P < 0.0001], 1.16 (95%CI = 1.08-1.24, P = 0.023), 1.08 (95%CI = 1.02-1.13, P = 0.006), and 1.12 (95%CI = 1.07-1.18, P < 0.0001), respectively. The effect of allele T of rs5219 was similar (OR = 1.16) in Europeans and Japanese. However, rs5219 was not associated with type 2 diabetes in the Chinese Han population. Our meta-analysis demonstrated that KCNJ11 and ABCC8 polymorphisms are associated with risk for type 2 diabetes in the global population. Comparative genomics and bioinformatics analyses revealed that rs5210 is located within a conserved 3'-UTR, and that allele A may abolish the binding site of hsa-miR-1910 that the risk allele G possesses.
钾内向整流通道亚家族J成员11（KCNJ11）和ATP结合盒亚家族C（CFTR/MRP）成员8（ABCC8）与2型糖尿病的关联性已在不同种族人群中进行了研究，但结果相互矛盾。我们对KCNJ11的rs5219、rs5210、rs5215以及ABCC8的rs757110进行了全面的荟萃分析，以评估这些区域对2型糖尿病遗传易感性的影响。我们在荟萃分析中纳入并使用了41项关于KCNJ11和ABCC8基因多态性与2型糖尿病的病例对照关联研究，涉及61,879名受试者。该疾病与rs5219 T、rs5210 G、rs5215 G和rs757110 G等位基因关联的合并比值比（OR）分别为1.15 [95%置信区间（95%CI）= 1.10 - 1.21，P < 0.0001]、1.16（95%CI = 1.08 - 1.24，P = 0.023）、1.08（95%CI = 1.02 - 1.13，P = 0.006）和1.12（95%CI = 1.07 - 1.18，P < 0.0001）。rs5219的T等位基因在欧洲人和日本人中的作用相似（OR = 1.16）。然而，rs5219在中国汉族人群中与2型糖尿病无关。我们的荟萃分析表明，KCNJ11和ABCC8基因多态性与全球人群的2型糖尿病风险相关。比较基因组学和生物信息学分析显示，rs5210位于保守的3'-UTR内，风险等位基因G所具有的A等位基因可能会消除hsa-miR-1910的结合位点。
