Association studies of genetic variation in the WFS1 gene and type 2 diabetes in UK populations
Association studies of genetic variation in the WFS1 gene and type 2 diabetes in UK populations
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DOI：
10.2337/diabetes.51.4.1287
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发表时间：
2002-04-01
期刊：
影响因子：
7.7
通讯作者：
Frayling, TM
中科院分区：
文献类型：
--
作者：
Minton, JAL;Hattersley, AT;Frayling, TM
WFS1 基因突变会导致 β 细胞死亡，从而导致一种称为 Wolfram 综合征的单基因糖尿病。 WFS1 变异在 2 型糖尿病易感性中的作用尚不清楚。我们对 29 名 2 型糖尿病先证者的 WFS1 基因进行了测序，并鉴定了 12 个编码变异。我们使用 152 个亲子三人组来寻找家族关联；残基 456 处的 R 等位基因（P = 0.04）和残基 611 处的 H 等位基因（P = 0.05）以及 R456-H611 单倍型（P = 0.032）过度传递给来自杂合父母的受影响后代。在另一组由 327 名 2 型糖尿病受试者和 357 名血糖正常对照受试者组成的队列中，H611 等位基因和 R456-H611 单倍型在比对照受试者更多的 2 型糖尿病受试者中出现（分别为单尾 P = 0.06 和 P = 0.023）。在一项综合分析中，H611 等位基因存在于 60% 的所有糖尿病染色体和 55% 的所有对照染色体中（比值比 [OR] 1.24 [95% CI 1.03-1.48]，P = 0.02），并且 R456-H611 单倍型在 2 型糖尿病受试者中的出现频率显着高于对照受试者（60% vs. 54%，OR） 1.29 [95% CI 1.08-1.54]，P = 0.0053）。我们的结果提供了第一个证据，证明 WFS1 基因的变异可能影响 2 型糖尿病的易感性。
Mutations in the WFS1 gene cause beta-cell death, resulting in a monogenic form of diabetes known as Wolfram syndrome. The role of variation in WFS1 in type 2 diabetes susceptibility is not known. We sequenced the WFS1 gene in 29 type 2 diabetic probands and identified 12 coding variants. We used 152 parent-offspring trios to look for familial association; the R allele at residue 456 (P = 0.04) and the H allele at residue 611 (P = 0.05) as well as the R456-H611 haplotype (P = 0.032) were overtransmitted to affected offspring from heterozygous parents. In a further cohort of 327 type 2 diabetic subjects and 357 normoglycemic control subjects, the H611 allele and the R456-H611 haplotype were present in more type 2 diabetic subjects than control subjects (one-tailed P = 0.06 and P = 0.023, respectively). In a combined analysis, the H611 allele was present in 60% of all diabetes chromosomes and 55% of all control chromosomes (odds ratio [OR] 1.24 [95% CI 1.03-1.48], P = 0.02), and the R456-H611 haplotype was significantly more frequent in type 2 diabetic subjects than in control subjects (60 vs. 54%, OR 1.29 [95% CI 1.08-1.54], P = 0.0053). Our results provide the first evidence that variation in the WFS1 gene may influence susceptibility to type 2 diabetes.