Association of the Vitamin D Metabolism Gene CYP27B1 With Type 1 Diabetes.
Bailey, Rebecca 1; Cooper, Jason D. 1; Zeitels, Lauren 1; Smyth, Deborah J. 1; Yang, Jennie H.M. 1; Walker, Neil M. 1; Hypponen, Elina 2; Dunger, David B. 3; Ramos-Lopez, Elizabeth 4; Badenhoop, Klaus 4; Nejentsev, Sergey 1; Todd, John A. 1
[Article]
Diabetes.
56(10):2616-2621, October 2007.
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OBJECTIVE: Epidemiological studies have linked vitamin D deficiency with the susceptibility to type 1 diabetes. Higher levels of the active metabolite 1[alpha],25-dihydroxyvitamin D (1[alpha],25(OH)2D) could protect from immune destruction of the pancreatic [beta]-cells. 1[alpha],25(OH)2D is derived from its precursor 25-hydroxyvitamin D by the enzyme 1[alpha]-hydroxylase encoded by the CYP27B1 gene and is inactivated by 24-hydroxylase encoded by the CYP24A1 gene. Our aim was to study the association between the CYP27B1 and CYP24A1 gene polymorphisms and type 1 diabetes.
RESEARCH DESIGN AND METHODS: We studied 7,854 patients with type 1 diabetes, 8,758 control subjects from the U.K., and 2,774 affected families. We studied four CYP27B1 variants, including common polymorphisms -1260C>A (rs10877012) and 2838T>C (rs4646536) and 16 tag polymorphisms in the CYP24A1 gene.
RESULTS: We found evidence of association with type 1 diabetes for CYP27B1 -1260 and 2838 polymorphisms, which are in perfect linkage disequilibrium. The common C allele of CYP27B1 -1260 was associated with an increased disease risk in the case-control analysis (odds ratio for the C/C genotype 1.22, P = 9.6 x 10-4) and in the fully independent collection of families (relative risk for the C/C genotype 1.33, P = 3.9 x 10-3). The combined P value for an association with type 1 diabetes was 3.8 x 10-6. For the CYP24A1 gene, we found no evidence of association with type 1 diabetes (multilocus test, P = 0.23).
CONCLUSIONS: The present data provide evidence that common inherited variation in the vitamin D metabolism affects susceptibility to type 1 diabetes.
(C) 2007 by the American Diabetes Association, Inc.