Polymorphism of Fc receptor IIa for immunoglobulin G is associated with placental malaria, in HIV-1-positive women in western Kenya

Background. Genetic polymorphism of the Fc receptor IIa for immunoglobulin (Ig) G (FcγRIIa) determines IgG subclass binding. Previous studies have shown that individuals with the IgG1/3-binding FcγRIIa-Arg/Arg131 genotype are relatively protected against high-density malaria, whereas individuals with the IgG2-binding FcγRIIa-His/His131 genotype are at increased risk for developing cerebral malaria. The present study was undertaken to examine the relationship between FcγRIIa polymorphism and placental malaria (PM) in pregnant women of known human immunodeficiency virus (HIV)-1 status. Methods. FcγRIIa genotype was determined in 903 pregnant women who had participated in a study designed to assess the effect that PM has on vertical transmission of HIV-1. FcγRIIa polymorphism was assessed in relation to PM. Results. Among HIV-negative women, there was no difference in the distribution of the FcγRIIa polymorphism by PM status. However, among HIV-positive women, the frequency of the FcγRIIa-His/His131 genotype was significantly higher in women with PM than in women without PM (31% vs. 22%, respectively [P = .032]). In multivariate analysis, the adjusted odds ratio for PM in HIV-positive women with the FcγRIIa-His/His131 genotype versus women in the FcγRIIa-His/Arg131 reference group was 1.72 (95% confidence interval, 1.11-2.69 [P = .016]). Conclusions. The present study suggests that the IgG2-binding FcγRIIa-His/His131 genotype is associated with enhanced susceptibility to PM in HIV-positive women but not in HIV-negative women.