Analysis of the Vitamin D Receptor Gene Sequence Variants in Type 1 Diabetes
- Sergey Nejentsev,
- Jason D. Cooper1,
- Lisa Godfrey1,
- Joanna M.M. Howson1,
- Helen Rance1,
- Sarah Nutland1,
- Neil M. Walker1,
- Cristian Guja2,
- Constantin Ionescu-Tirgovişte2,
- David A. Savage3,
- Dag E. Undlien4,
- Kjersti S. Rønningen5,
- Eva Tuomilehto-Wolf6,
- Jaakko Tuomilehto67,
- Kathleen M. Gillespie8,
- Susan M. Ring9,
- David P. Strachan10,
- Barry Widmer11,
- David Dunger11 and
- John A. Todd1
- 1Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute of Medical Research, University of Cambridge, Cambridge, U.K
- 2Clinic of Diabetes, Institute of Diabetes, Nutrition and Metabolic Diseases “N. Paulescu,” Bucharest, Romania
- 3Department of Medical Genetics, Queen’s University, Belfast, U.K
- 4Institute of Medical Genetics, Ulleval University Hospital, University of Oslo, Oslo, Norway
- 5Laboratory of Molecular Epidemiology, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway
- 6Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland
- 7Department of Public Health, University of Helsinki, Helsinki, Finland
- 8Department of Clinical Science at North Bristol, Division of Medicine, University of Bristol, Bristol, U.K
- 9Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), University of Bristol, Bristol, U.K
- 10Department of Community Health Sciences, St. George’s Hospital Medical School, London, U.K
- 11Department of Paediatrics, University of Cambridge, Cambridge, U.K
- Address correspondence and reprint requests to Sergey Nejentsev, MD, PhD, JDRF/WT DiabetesInflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, WT/MRC building, Addenbrooke’s Hospital, Cambridge, CB2 2XY, U.K. E-mail: sergey.nejentsev{at}cimr.cam.ac.uk
Abstract
Vitamin D is known to modulate the immune system, and its administration has been associated with reduced risk of type 1 diabetes. Vitamin D acts via its receptor (VDR). Four single nucleotide polymorphisms (SNPs) of the VDR gene have been commonly studied, and evidence of association with type 1 diabetes has been reported previously. We sequenced the VDR gene region and developed its SNP map. Here we analyzed association of the 98 VDR SNPs in up to 3,763 type 1 diabetic families. First, we genotyped all 98 SNPs in a minimum of 458 U.K. families with two affected offspring. We further tested eight SNPs, including four SNPs associated with P < 0.05 in the first set and the four commonly studied SNPs, in up to 3,305 additional families from the U.K., Finland, Norway, Romania, and U.S. We only found weak evidence of association (P = 0.02–0.05) of the rs4303288, rs12721366, and rs2544043 SNPs. We then tested these three SNPs in an independent set of 1,587 patients and 1,827 control subjects from the U.K. and found no evidence of association. Overall, our results indicate that common sequence variation in the VDR gene has no major effect in type 1 diabetes in the populations tested.
Footnotes
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Additional information for this article can be found in an online appendix available at http://diabetes.diabetesjournals.org.
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- Accepted June 24, 2004.
- Received April 2, 2004.
- DIABETES
