Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes.: The Finnish diabetes Prevention Study
Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes.: The Finnish diabetes Prevention Study
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DOI：
10.1210/jc.2004-1204
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发表时间：
2004-12-01
影响因子：
5.8
通讯作者：
Laakso, M
中科院分区：
文献类型：
--
作者：
Laukkanen, O;Pihlajamäki, J;Laakso, M
2型糖尿病是由胰岛素分泌缺陷和胰岛素作用受损引起的。我们调查了参与芬兰糖尿病预防研究的490名糖耐量受损的受试者中，SUR1和Kir6.2基因的常见多态是否与2型糖尿病风险增加有关。SUR1基因的1273AGA等位基因与2型糖尿病的2倍风险相关[优势比(OR)，2.00；95%可信区间(CI)，1.19~3.36；P=0.009]。该沉默多态与G-2886A、G-1561A和A-1273G三个启动子多态存在连锁不平衡，形成高危单倍型，使2型糖尿病的发病风险增加2倍(OR值为1.89；95%可信区间为1.09~3.27；P=0.023)。同时具有高危单倍型和Kir6.2基因23K等位基因的受试者转化为糖尿病的风险是无这两种高危单倍型受试者的6倍(OR，5.68；95%CI，1.75~18.32；P=0.004)。我们的结论是，SUR1基因的多态预测了糖耐量受损向2型糖尿病的转化，并且这些多态对糖尿病风险的影响与Kir6.2基因的E23K多态是相加的。
Type 2 diabetes is caused by defective insulin secretion and impaired insulin action. We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study. The 1273AGA allele of the SUR1 gene was associated with a 2-fold risk of type 2 diabetes [ odds ratio (OR), 2.00; 95% confidence interval (CI), 1.19-3.36; P = 0.009]. This silent polymorphism was in linkage disequilibrium with three promoter polymorphisms (G-2886A, G-1561A, and A-1273G), and they formed a high-risk haplotype having a 2-fold risk of type 2 diabetes (OR, 1.89; 95% CI, 1.09-3.27; P = 0.023). Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004). We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene.