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

Rebecca Bailey, Jason D. Cooper, Lauren Zeitels, Deborah J. Smyth, Jennie H M Yang, Neil M. Walker, Elina Hyppönen, David B. Dunger, Elizabeth Ramos-Lopez, Klaus Badenhoop, Sergey Nejentsev, John A. Todd

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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 1α,25-dihydroxyvitamin D (1α,25(OH)2D) could protect from immune destruction of the pancreatic β-cells. 1α,25(OH)2D is derived from its precursor 25-hydroxyvitamin D by the enzyme 1α-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 × 10-4) and in the fully independent collection of families (relative risk for the C/C genotype 1.33, P = 3.9 × 10-3). The combined P value for an association with type 1 diabetes was 3.8 × 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.

    Original languageEnglish
    Pages (from-to)2616-2621
    Number of pages6
    Issue number10
    Publication statusPublished - Oct 2007

    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism

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