Role of the Fc gamma receptor IIA polymorphism in the antiphospholipid syndrome - an international meta-analysis

Objective. To assess the impact of the FcgammaRIIA-R/H131 polymorphism on the risk for antiphospholipid syndrome (APS), both primary and secondary to systemic lupus erythematosus (SLE). Methods. This international meta-analysis combined data from 9 research teams. FcgammaRIIA-R/H131 genotypes were determined in 481 APS cases (206 with primary APS), 1,420 SLE controls, and 1,655 disease-free controls. Data were combined using fixed-effects and random-effects models. Results. Compared with disease-free controls, the RR genotype was enriched in the entire group of APS cases (odds ratio [OR] 1.65, 95% confidence interval [95% CI] 1.28-2.14); this was driven mostly by patients with secondary APS (OR 1.95, 95% CI 1.45-2.63). The excess of RR homozygotes but not heterozygotes among APS patients suggested a recessive mode of inheritance, rather than the additive model seen for SLE susceptibility, where RR conferred greatest risk, and RH intermediate risk, for SLE. This probably reflected the additional influence of another opposing genetic effect of HH homozygosity on APS predisposition (OR 0.72 for RH versus HH, 95% CI 0.55-0.96). Among SLE patients, those with APS were more frequently HH homozygotes than heterozygotes (OR 0.56 for RH versus HH, 95% CI 0.39-0.81). HH homozygosity also tended to predominate in primary APS compared with secondary A-PS (OR 0.50 for RR versus HH, 95% CI 0.25-0.99 by fixed-effects model). There was no significant between-study heterogeneity for any of these effects. Conclusion. The FcgammaRIIA-R/H131 polymorphism is an important determinant of predisposition to APS, with different influences on SLE and APS susceptibility per se.