Role of the Fcγ receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: A meta‐analysis

Abstract

Objective. To assess the impact of the Fc␥ receptor type IIa (Fc␥RIIa)-R/H131 polymorphism on the risk for systemic lupus erythematosus (SLE) and development of lupus nephritis.Methods. A meta-analysis was performed based on the Medline and Embase databases (last retrieval August 2001), assessment of bibliographies of pertinent articles, and additional data gathered after contact with primary investigators.Results. A total of 25 comparisons from 17 studies involving R/H131 genotyping of 1,405 patients with lupus nephritis, 1,709 SLE patients without nephritis, and 2,580 non-SLE controls were included. No association between RR genotype and risk of lupus nephritis relative to both other genotypes (odds ratio [OR] 1.05, 95% confidence interval [95% CI] 0.88-1.27) was demonstrated in the total meta-analysis or in any racial subgroup. The RR genotype was more frequent in SLE patients as a whole (OR 1.30, 95% CI 1.10-1.52) and in SLE patients without nephritis (OR 1.27, 95% CI 1.04-1.55) compared with disease-free controls. A potential dose-response relation between the R131 allele and the risk of SLE was also identified, with an OR of 1.23 for RR versus RH (95% CI 1.03-1.46). The OR was 1.55 for RR versus HH (95% CI 1.21-1.98). There was no significant heterogeneity between racial subgroups. The population-attributable fractions of SLE cases due to the Fc␥RIIa-R131 allele were 13%, 40%, and 24% in subjects of European, African, and Asian descent, respectively.Conclusion. The Fc␥RIIa-R/H131 polymorphism represents a significant risk factor for SLE but has no clear effect on susceptibility for lupus nephritis.

Association of Fcγ receptor IIA, but not IIB and IIIA, polymorphisms with systemic lupus erythematosus: A family‐based association study in Caucasians

“…Our results in the family-based association studies provide supportive evidence for the findings of the metaanalysis of case-control association studies, which demonstrated significant association of FCGR2A-131R (11). On the other hand, we failed to replicate the association of FCGR3A-176F with the presence of lupus nephritis, which was shown in the meta-analysis of FCGR3A (12).…”

“…Recently, the first family-based association study on FCGR polymorphisms in SLE was reported (10); the authors described significant transmission of FCGR3A-176F in European American and African American SLE families. In addition, recent large-scale meta-analyses of case-control association studies convincingly demonstrated that FCGR2A-131R is an important risk factor for SLE (11), while FCGR3A-176F is associated with the development of lupus nephritis rather than with SLE per se (12).…”

Role of the Fcγ receptor IIA polymorphism in the antiphospholipid syndrome: An international meta‐analysis

“…Research teams worldwide working on the low-affinity Fc␥R and their association with autoimmune diseases were invited to contribute data, provided that their study patients met the eligibility criteria defined above. We contacted teams identified as part of a previous meta-analysis that examined the role of the Fc␥RIIA-R/H131 polymorphism in SLE and lupus nephritis (9). Other potentially relevant studies were sought by searches of the Medline and EMBase databases (last search August 2002), with various combinations of key words ("antiphospholipid," "anticardiolipin," "polymorphism," "allele," "genetics," "Fc receptor," and "Fc␥ receptor").…”

“…This polymorphism has been proposed to be influential in a variety of autoimmune diseases (7). The low-binding R131 allele imparts a significant risk for systemic lupus erythematosus (SLE) (9). Binding to the H131 variant can initiate more pronounced monocyte, platelet, and endothelial cell activation in the context of an IgG2 immune response, inducing a prothrombotic phenotype.…”

“…However, the data are not yet conclusive (12,13). Besides, in patients with APS secondary to SLE, this anticipated selection of the H131 allele may not be evident, given the overrepresentation of the RR genotype in SLE (9). Thus, the role of the Fc␥RIIA-R/H131 polymorphism in APS is still unclear.…”