Vitamin D receptor (VDR) gene polymorphism and risk of rheumatoid arthritis (RA): systematic review and meta-analysis

Vitamin D is involved in immune system modulation as well as in calcium and bone homeostasis, hence plays a role in rheumatoid arthritis (RA) etiopathogenesis. A bulk of studies in different populations have assessed the association between the vitamin D receptor (VDR) gene polymorphisms and the risk of RA, reporting conflicting results. Therefore, we designed a meta-analysis to comprehensively evaluate the association of VDR gene polymorphisms and RA risk. All potential studies reporting the association between VDR gene polymorphisms and susceptibility to RA published till February 2020 were retrieved through systematic search of database, including Scopus and MEDLINE. Strength of pooled association was determined through calculating the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analysis was performed by stratifying the studies by population type. This meta-analysis included 23 eligible studies (21 articles) overall. We noticed that FokI SNP had a significant protective association with susceptibility to RA in the overall analysis as well as in Europeans and Asians. TaqI SNP decreased the RA risk in Africans and Arabs, but not in the overall analysis. Likewise, BsmI SNP and RA risk in the overall population analysis was not significant. Interestingly, BsmI polymorphism increased RA risk in Africans. This meta-analysis offers a significant association between VDR gene polymorphism and susceptibility to RA in both overall and ethnic-specific analysis. However, different polymorphisms acted inversely in increasing or decreasing RA risk in different populations.