Role of the Fc gamma receptor IIIA-V/F158 polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis

Objective: To perform a meta-analysis to assess the risk of the Fc-gamma receptor type IIIA (Fc gamma RIIIA)-V/F158 polymorphism for lupus nephritis and systemic lupus erythematosus (SLE). Methods: We surveyed studies on V/F158 and SLE and/or lupus nephritis using Medline, Blackwell, and EMBASE databases up to January 2009. Sufficient original data were available to calculate odds ratios (ORs) for SLE and/or lupus nephritis based on the American College of Rheumatology (ACR) criteria. Two investigators independently assessed the data quality and extracted the data. Results: The F158 allele presented overall consistent association evidence for SLE, SLE without nephritis, and lupus nephritis [OR 1.27, 95% confidence interval (CI) 1.13-1.43; OR 1.20, 95% CI 1.05-1.37; OR 1.15, 95% CI 1.04-1.28, respectively]. FF homozygosity had a dose-response relationship for SLE with maximal OR 1.68 (95% CI 1.26-2.23). It also strongly influenced the risk of lupus nephritis and of SLE without nephritis, with maximal OR 1.30 (95% CI 1.04-1.64) and 1.43 (95% CI 1.07-1.92), respectively. Ethnic subgroup analyses revealed that the F158 allele was significantly higher in SLE patients of European and Asian descent [OR 1.30 (95% CI 1.07-1.58) and OR 1.24 (95% CI 1.04-1.48), respectively] but not in SLE patients of African descent and was only highly associated with lupus nephritis in those of Asian descent [OR 1.26 (95% CI 1.06-1.50)]. The FF genotype was significantly associated with SLE in those of European and Asian descent, with maximal OR 1.61 (95% CI 1.03-2.53) and 1.70 (95% CI 1.12-2.58), respectively, but not for lupus nephritis and SLE without nephritis of any subgroup. Conclusions: The Fc gamma RIIIA-V/F158 polymorphism might be a common susceptibility factor for SLE and lupus nephritis and play an important role in the overall development of SLE, showing different risks within ethnic populations, which should provide novel insights into the pathogenesis of the disease.