American Journal of Epidemiology Advance Access published online on June 13, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn142
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Variation in Associations between Allelic Variants of the Vitamin D Receptor Gene and Onset of Type 1 Diabetes Mellitus by Ambient Winter Ultraviolet Radiation Levels: A Meta-Regression Analysis
1 Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia
2 Menzies Research Institute, University of Tasmania, Hobart, Australia
3 Department of Physiology, School of Medicine, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
4 Department of Paediatrics, School of Medicine, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
5 School of Population Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
Correspondence to Professor Anne-Louise Ponsonby, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia (e-mail: anne-louise.ponsonby{at}mcri.edu.au).
Received for publication December 21, 2007. Accepted for publication May 2, 2008.
Vitamin D receptor (VDR) gene polymorphisms may be associated with risk of developing type 1 diabetes mellitus (T1DM), but reports have been conflicting. The authors reexamined population-based case-control studies on selected VDR polymorphisms and T1DM to investigate whether variation in reported associations could be partly explained by differences in ambient winter ultraviolet radiation (UVR) levels. A meta-analysis of 16 studies from 19 regions (midwinter UVR range, 1.0–133.8 mW/m2) was conducted. The association between winter UVR and the log odds ratio was examined by meta-regression. For FokI and BsmI, the log odds ratio for the association between the F and B alleles and T1DM increased as regional winter UVR increased (p = 0.039 and p = 0.036, respectively). The association between the TaqI T allele and T1DM was reduced with increasing winter UVR (p = 0.040). Low winter regional UVR was associated with a higher proportion of controls carrying BsmI and ApaI uppercase alleles and a lower proportion of controls carrying TaqI uppercase alleles. These findings strengthen the case that VDR variants are involved in the etiology of T1DM. They suggest that environmental UVR may influence the association between VDR genotype and T1DM risk. Further work on VDR polymorphisms and T1DM should concomitantly examine the roles of past UVR exposure and vitamin D status.
diabetes mellitus, type 1; genetics; receptors, calcitriol; ultraviolet rays; vitamin D
Abbreviations: CI, confidence interval; UVR, ultraviolet radiation; VDR, vitamin D receptor