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© 2002 by the American Diabetes Association, Inc.
Brief Genetics Reports |
Association Studies of Genetic Variation in the WFS1 Gene and Type 2 Diabetes in U.K. Populations
1 Section of Medical and Molecular Genetics, Department of Pediatrics and Child Health, The Medical School, University of Birmingham, Edgbaston, U.K.
2 Department of Diabetes and Vascular Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, U.K.
3 Imperial College Genetics and Genomics Research Institute and Division of Medicine, Imperial College, London, U.K.
4 Department of Medicine, Medical School, University of Newcastle, Newcastle, U.K.
Mutations in the WFS1 gene cause ß-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.
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