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Diabetes Publish Ahead of Print published online ahead of print July 2, 2007
DOI: 10.2337/db07-0652
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Original Research

Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes

Rebecca Bailey1, Jason D. Cooper1, Lauren Zeitels1, Deborah J. Smyth1, Jennie H.M. Yang1, Neil M. Walker1, Elina Hyppönen2, David B. Dunger3, Elizabeth Ramos-Lopez4, Klaus Badenhoop4, Sergey Nejentsev1, and John A. Todd1

1 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, UK
2 Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London, UK
3 Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
4 Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital, Frankfurt, Germany

Correspondence: john.todd{at}cimr.cam.ac.uk

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, could protect from immune destruction of the pancreatic ß cells. 1{alpha},25-dihydroxyvitamin D 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 and 8,758 controls from Great Britain 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 (OR = 1.07, P = 2.9 x 10-3), and in the fully independent collection of families (RR = 1.11, P = 6.4 x 10-3). The combined support of an association for CYP27B1 -1260 is P = 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 provides evidence that common inherited variation in the vitamin D metabolism affects susceptibility to type 1 diabetes.


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