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Association of the Vitamin D Metabolism Gene CYP27B1 With Type 1 Diabetes
Ist Teil von
Diabetes (New York, N.Y.), 2007-10, Vol.56 (10), p.2616-2621
Ort / Verlag
Alexandria, VA: American Diabetes Association
Erscheinungsjahr
2007
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Association of the Vitamin D Metabolism Gene CYP27B1 With Type 1 Diabetes
Rebecca Bailey 1 ,
Jason D. Cooper 1 ,
Lauren Zeitels 1 ,
Deborah J. Smyth 1 ,
Jennie H.M. Yang 1 ,
Neil M. Walker 1 ,
Elina Hyppönen 2 ,
David B. Dunger 3 ,
Elizabeth Ramos-Lopez 4 ,
Klaus Badenhoop 4 ,
Sergey Nejentsev 1 and
John A. Todd 1
1 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical
Research, University of Cambridge, U.K
2 Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London, U.K
3 Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, U.K
4 Department of Internal Medicine I, Division of Endocrinology, Diabetes, and Metabolism, University Hospital, Frankfurt, Germany
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) 2 D) could protect from immune destruction of the pancreatic β-cells. 1α,25(OH) 2 D 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.
1α,25(OH)2D, 1α,25-dihydroxyvitamin D
25(OH)D, 25-hydroxyvitamin D
EFSD, European Foundation for the Study of Diabetes
IL, interleukin
MAF, minor allele frequency
NCBI, National Center for Biotechnology Information
SNP, single nucleotide polymorphism
VDR, vitamin D receptor
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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