The FcγRIIIA-F158 allele is a risk factor for the development of lupus nephritis:: A meta-analysis

Background. The FcgammaRIIIA-V/F158 polymorphism affects immunoglobulins (Ig)G1- and IgG3-binding capacity and may modulate the expression of renal disease in patients with systemic lupus erythematosus (SLE). We aimed to determine whether this polymorphism confers risk for the development of lupus nephritis and SLE in general. Methods. A meta-analysis was performed based on the Medline and Embase databases (last update, August 2002), perusal of abstracts from major meetings (1999 to 2001), assessment of bibliographies of pertinent articles, and additional data gathered after contact with primary investigators. Results. A total of 16 comparisons from 11 studies involving V/F158 genotyping of 1154 patients with lupus nephritis, 1261 SLE patients without nephritis, and 1455 disease-free controls were included. Comparison of lupus nephritis patients with non-nephritis SLE subjects revealed a significant overrepresentation of the low-binding F158 allele among patients who developed renal disease [odds ratio (OR) 1.20, 95% confidence interval (95% CI) 1.06 to 1.36, P = 0.003)], without significant between-study heterogeneity. FF homozygotes had the highest risk of renal disease as compared to VV homozygotes (OR 1.47, 95% CI 1.11 to 1.93, P = 0.006). It was uncertain whether the F158 allele influenced susceptibility to SLE per se (OR 1.19, 95% CI 0.99 to 1.43, P = 0.063 for SLE patients without nephritis versus disease-free controls; 0.01 < P < 0.10 for heterogeneity) and the observed trend for an association was driven mostly by the smaller studies (P = 0.058 for publication bias). No such bias was detected for analyses on susceptibility to lupus nephritis. Conclusion. The FcgammaRIIIA-V/F158 polymorphism has a significant impact on the development of lupus nephritis.