Genetics of the APM1 locus and its contribution to type 2 diabetes susceptibility in French Caucasians
Genetics of the APM1 locus and its contribution to type 2 diabetes susceptibility in French Caucasians
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DOI：
10.2337/diabetes.53.11.2977
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发表时间：
2004-11-01
期刊：
影响因子：
7.7
通讯作者：
Froguel, P
中科院分区：
文献类型：
--
作者：
Gibson, F;Froguel, P
我们对APM1基因座的遗传学及其对法国高加索人群2型糖尿病易感性的遗传基础的贡献进行了详细的重新检查。APM1启动子单核苷酸多态性-11426的G等位基因与2型糖尿病有一定的相关性（优势比1.44 [95% CI 1.04-1.98]; P = 0.03），为APM1启动子区域单核苷酸多态性与2型糖尿病的遗传风险有关提供了确凿的证据。“滑动窗口”分析发现，单倍型1-1-1、1-1-1和1-1-1-1对2型糖尿病有很强的保护作用（P <或等于0.0001）。有证据表明，APM1基因是一个低连锁不平衡、高单倍型多样性和高重组的位点。我们无法获得数据来支持APM1基因的遗传变异是染色体3q27上2型糖尿病连锁结果的主要因素这一假设。最后，在早发型2型糖尿病的家庭中，我们获得了血清脂联素水平连锁峰值（对数比值= 2.1）的暗示证据，该连锁峰值与2型糖尿病连锁峰值的位置密切匹配。这一结果表明，2型糖尿病易感位点3q27既影响2型糖尿病的遗传易感性，也影响2型糖尿病患者血清脂联素水平。
We have carried out a detailed reexamination of the genetics of the APM1 locus and its contribution to the genetic basis of type 2 diabetes susceptibility in the French Caucasian population. The G allele of single nucleotide polymorphism -11426 in the APM1 promoter showed modest association with type 2 diabetes (odds ratio 1.44 [95% CI 1.04-1.98]; P = 0.03), providing corroborative evidence that single nucleotide polymorphisms in the APM1 promoter region contribute to the genetic risk of type 2 diabetes. A "sliding window" analysis identified haplotypes 1-1-1, 1-1-1-1, and 1-1-1-1-1 as being strongly protective against type 2 diabetes (P less than or equal to 0.0001). Evidence is presented that the APM1 gene is a locus of low linkage disequilibrium, high haplotype diversity, and high recombination. We were unable to obtain data to support the hypothesis that genetic variation in the APM1 gene is a major contributor to the type 2 diabetes linkage result at chromosome 3q27. Finally, in families with early-onset type 2 diabetes, we obtained suggestive evidence of a linkage peak for serum adiponectin levels (logarithm of odds = 2.1) that closely matched the position of the type 2 diabetes linkage peak. This result indicated that the type 2 diabetes susceptibility locus at 3q27 influences both genetic predisposition to type 2 diabetes and serum adiponectin levels in patients with type 2 diabetes.