Vitamin D Receptor Polymorphisms and Rheumatoid Arthritis Risk: A Systematic Review and Meta-Analysis Evaluating the...

Area of Science:

• Genetics
• Rheumatology
• Epidemiology

Background:

• Previous studies on vitamin D receptor (VDR) polymorphisms (ApaI, BsmI, TaqI, FokI) and rheumatoid arthritis (RA) have yielded conflicting results.
• The influence of clinical and population-level factors on the VDR-RA association remains unclear.

Purpose of the Study:

• To conduct a comprehensive meta-analysis evaluating the association between VDR polymorphisms and RA risk.
• To investigate whether ethnicity, disease severity (bone erosion), and classification criteria moderate this relationship.

Main Methods:

• Systematic review of multiple databases (PubMed, Scopus, etc.) up to July 2024.
• Inclusion of 25 case-control studies (3711 RA patients, 3884 controls).
• Random-effects meta-analyses, subgroup analyses, and meta-regression were employed, with quality assessed by the Newcastle-Ottawa Scale.

Main Results:

• No overall significant association between VDR polymorphisms and RA was found across genetic models.
• Subgroup analyses revealed ethnic variations: South Asians showed reduced RA likelihood with ApaI (OR=0.26) and BsmI, while Africans had increased RA likelihood with BsmI (OR=1.77).
• Meta-regression identified ethnicity, classification criteria, and bone erosion as significant moderators; bone erosion increased RA likelihood for FokI (OR=2.21).

Conclusions:

• The association between VDR polymorphisms and RA risk is not uniform.
• Ethnicity, classification criteria, and disease severity (bone erosion) are crucial moderating factors.
• Future genetic association studies in RA must account for population and clinical heterogeneity.