Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations.
Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations.
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DOI：
10.1007/s00125-007-0887-6
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发表时间：
2008-03
期刊：
影响因子：
8.2
通讯作者：
Sandhu, M. S.
中科院分区：
文献类型：
--
作者：
Franks, P. W.;Rolandsson, O.;Debenham, S. L.;Fawcett, K. A.;Payne, F.;Dina, C.;Froguel, P.;Mohlke, K. L.;Willer, C.;Olsson, T.;Wareham, N. J.;Hallmans, G.;Barroso, I.;Sandhu, M. S.
编码Wolframin的基因WFS1发生突变会导致沃尔夫勒姆综合征，这是一种罕见的神经系统疾病。最近有报道称WFS1的单核苷酸多态性（SNP）与2型糖尿病之间存在关联。在本研究中，我们试图在瑞典北部一项针对2型糖尿病的病例对照研究中重复这些关联。我们还对来自瑞典、芬兰和法国已发表及先前未发表的数据进行了荟萃分析，以获得最新的综合效应估计值。
在一项针对瑞典成年人的2型糖尿病病例对照研究（病例数 = 1296，对照数 = 1412）中，对四个WFS1的SNP（rs10010131、rs6446482、rs752854、rs734312 [R611H]）进行了基因分型。在对年龄、性别和体重指数进行调整后，使用逻辑回归来评估每个WFS1的SNP与2型糖尿病之间的关联。然后我们对11项2型糖尿病研究进行了荟萃分析，这些研究包含多达14139例病例和16109例对照，以获得WFS1变异体的综合效应估计值。
在瑞典北部的研究中，rs752854的次要等位基因与2型糖尿病风险降低相关（比值比 = 0.85；95%置信区间 = 0.75 - 0.96；p = 0.010）。其余的SNP观察到了临界的统计学关联。对SNP rs10010131或其替代变异体的四项独立重复研究的荟萃分析显示出存在统计学关联的证据（比值比 = 0.87；95%置信区间 = 0.82 - 0.93；p = 4.5×10⁻⁵）。在对所有11项研究（包含14139例病例和16109例对照）的最新荟萃分析中，也观察到了存在统计学关联的有力证据（比值比 = 0.89；95%置信区间 = 0.86 - 0.92；p = 4.9×10⁻¹¹）。
在这项关于WFS1基因变异体与2型糖尿病风险的研究中，我们重复了先前报道的该基因座的SNP与2型糖尿病风险之间的关联。
Mutations at the Wolframin encoding gene, WFS1, cause Wolfram syndrome, a rare neurological condition. Associations between single nucleotide polymorphisms (SNPs) at WFS1 and type 2 diabetes have recently been reported. In the present study, we sought to replicate those associations in a northern Swedish case-control study for type 2 diabetes. We also meta-analyzed published and previously unpublished data from Sweden, Finland and France to obtain updated summary effect estimates. Four WFS1 SNPs (rs10010131, rs6446482, rs752854, rs734312 [R611H]) were genotyped in a type 2 diabetes case-control study (N=1,296/1,412) of Swedish adults. Logistic regression was used to assess the association between each WFS1 SNP and type 2 diabetes, following adjustment for age, sex, and body mass index. We then performed a meta-analysis of 11 studies of type 2 diabetes, comprising up to 14,139 cases and 16,109 controls, to obtain a summary effect estimate for the WFS1 variants. In the northern Swedish study, the minor allele at rs752854 was associated with reduced type 2 diabetes risk (OR=0.85; 95% CI=0.75-0.96; p=0.010). Borderline statistical associations were observed for the remaining SNPs. The meta-analysis of the four independent replication studies for SNP rs10010131, or its proxy variants, showed evidence for statistical association (OR=0.87; 95% CI=0.82-0.93; p=4.5×10−5). In an updated meta-analysis of all 11 studies, comprising 14,139 cases and 16,109 controls, strong evidence for statistical association was also observed (OR=0.89; 95% CI=0.86-0.92; p=4.9×10−11). In this study of WFS1 gene variants and type 2 diabetes risk, we have replicated the previously reported associations between SNPs at this locus and risk of type 2 diabetes.
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