Vitamin D receptor ApaI, BsmI, Fok1, and TaqI gene polymorphisms and susceptibility to multiple sclerosis in an Iranian population: A systematic review and meta-analysis

Introduction:There are conflicting results regarding the exact effect of vitamin D receptors (VDR) polymorphisms on the development of multiple sclerosis (MS). All the current literature on the association between four different VDR gene polymorphisms and susceptibility to MS in the Iranian population is evaluated by systematic review and meta-analysis for the first time.Methods: Databases were searched for case-control studies evaluating the association between the VDR Apa-I, Bsm-I, Fok-I, and Taq-I gene polymorphisms and MS risk in Iran. Data were extracted and odds ratios (OR) with 95% confidence intervals (CI) were calculated.Results: ApaI polymorphism was the only VDR variant which showed statistically significant relation in allelic (OR=0.54 (95% CI: 0.37 – 0.79); P= 0.00), homozygote (OR=3.48 (95% CI: 1.7 – 6.9); P= 0.00), dominant (OR=0.56 (95% CI: 0.3 – 0.79); P= 0.01), and recessive (OR= 0.35 (95% CI: 0.18 – 0.66); P=0.00) models with MS in Iranian population. The TaqI polymorphism showed statistically significant association with MS only in homozygote model (OR= 0.28 (95% CI: 0.08 – 0.9); P= 0.04). The BsmI polymorphism also showed significant relation in allelic (OR= 0.69 (95% CI: 0.51 – 0.94); P= 0.01), homozygote (OR= 0.46 (95% CI: 0.25 – 0.86); P= 0.01), and recessive OR= 0.56 (95% CI: 0.39 – 0.8); P= 0.00) models with MS after performing sensitivity analysis. No important publication bias was observed among included studies. However, there was significantly high heterogeneity among the included studies based on the I2 index. Conclusion: In this study only VDR ApaI polymorphism and homozygous dominant of TT were associated with MS and BsmI and FokI showed no relation with MS pathogenesis in an Iranian population; however, results should be interpreted with caution and due to the low number of studies and relatively small sample size, the results are unable to come to a firm conclusion.