Association of the Vitamin D Metabolism Gene CYP27B1 With Type 1 Diabetes

  1. Rebecca Bailey1,
  2. Jason D. Cooper1,
  3. Lauren Zeitels1,
  4. Deborah J. Smyth1,
  5. Jennie H.M. Yang1,
  6. Neil M. Walker1,
  7. Elina Hyppönen2,
  8. David B. Dunger3,
  9. Elizabeth Ramos-Lopez4,
  10. Klaus Badenhoop4,
  11. Sergey Nejentsev1 and
  12. John A. Todd1
  1. 1Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, U.K
  2. 2Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London, U.K
  3. 3Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, U.K
  4. 4Department of Internal Medicine I, Division of Endocrinology, Diabetes, and Metabolism, University Hospital, Frankfurt, Germany
  1. Address correspondence and reprint requests to Prof. John A. Todd, Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, WT/MRC building, Addenbrooke's Hospital, Cambridge, CB2 0XY, U.K. E-mail: john.todd{at}cimr.cam.ac.uk

Abstract

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.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 2 July 2007. DOI: 10.2337/db07-0652.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0652.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted June 27, 2007.
    • Received May 15, 2007.
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  1. Diabetes vol. 56 no. 10 2616-2621
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