Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case-control studies.

Vitamin D receptor (VDR) polymorphisms have been studied as potential contributors to multiple sclerosis (MS). However, published studies differ with respect to study design and the significance of the effects detected. The aim of this study was to quantify the magnitude of the risk associated with the TaqI, BsmI, ApaI and FokI VDR polymorphisms in MS using a meta-analysis approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search and meta-analysis of the literature. Subgroup analyses were performed to detect potential sources of heterogeneity from the selected study characteristics. The stability of the summary risk was evaluated using sensitivity analyses. The meta-analysis included a total of 3300 cases and 3194 controls from 13 case-control studies. There were no significant associations found between TaqI and BsmI polymorphisms and MS risk. The association between the ApaI polymorphism and MS risk was significant in the homozygous and codominant models (P=0.013 and P=0.031, respectively), suggesting that the AA ApaI genotype might be a significant MS risk factor. Publication year and age significantly affected the association between TaqI polymorphisms and MS (P=0.014 and P=0.010, respectively), which indicates a protective effect of the major T allele. The AA ApaI and FF FokI genotypes are significant risk factors for MS. The association between the TaqI polymorphism and MS risk is significantly affected by study characteristics.