Vitamin D Receptor Polymorphisms and Rheumatoid Arthritis Risk: A Systematic Review and Meta-Analysis Evaluating the Moderating Effects of Ethnicity, Bone Erosion, and Classification Criteria

Background/Aims: Previous studies examining the association between vitamin D receptor (VDR) polymorphisms (ApaI, BsmI, TaqI, FokI) and rheumatoid arthritis (RA) have reported inconsistent findings. This metaanalysis aimed to evaluate whether clinical and population-level factors moderate this association.

Materials and Methods: A systematic review of PubMed, Web of Science, Scopus, Cochrane Library, ClinicalTrials.gov, and Google Scholar was conducted up to July 19, 2024. Observational studies comparing VDR polymorphisms between RA patients and healthy controls were included. Studies without a control group, with fewer than 20 cases, or lacking relevant outcome data were excluded. Methodological quality was assessed using the Newcastle–Ottawa Scale. Random-effects meta-analyses, subgroup analyses, and meta-regression were performed.

Results: Twenty-five case-control studies (3711 RA patients and 3884 controls) were included. No significant overall association was observed between VDR polymorphisms and RA across genetic models. However, subgroup analyses demonstrated ethnic variability, with reduced RA likelihood observed among South Asians for the ApaI dominant model (OR = 0.26, 95% CI: 0.14-0.49) and BsmI polymorphism, while African populations showed increased likelihood for BsmI under the recessive model (OR = 1.77, 95% CI: 1.13-2.78). Meta-regression identified ethnicity, classification criteria, and bone erosion as significant moderators; bone erosion was associated with increased RA likelihood for the FokI dominant model (OR = 2.21, 95% CI: 1.24-3.97).

Conclusion: Although no consistent overall association was identified, the relationship between VDR polymorphisms and RA appears to be modified by ethnicity, classification criteria, and disease severity. These findings underscore the importance of accounting for clinical and population heterogeneity in genetic association studies of RA.

Cite this article as: Liu W, Xi S. Vitamin D receptor polymorphisms and rheumatoid arthritis risk: A systematic review and meta-analysis evaluating the moderating effects of ethnicity, bone erosion, and classification criteria. Arch Rheumatol. 2026;41(3):168-187.