Fc gamma receptor IIa (CD32) polymorphism is associated with protection ofinfants against high-density Plasmodium falciparum infection. VII. Asembo Bay Cohort Project

In vitro studies have shown that inhibition of Plasmodium falciparum blood- stage parasite growth by antibody-dependent cellular inhibition is mediated by cooperation between malaria-specific IgG1 and IgG3, but not IgG2, and m onocytes via the Fc gamma receptor II (Fc gamma RII). A single amino acid s ubstitution at position 131 in Fc gamma RIIa is critical in the binding of human IgG subclasses. The hypothesis that the Fc gamma RIIa-Arg/Arg131 geno type, which does not bind to IgG2, is a host genetic factor for protection against high-density P. falciparum infection was tested. One hundred eighty -two infants from a large community-based birth cohort study in western Ken ya were selected for an unmatched case-control study. Results showed that t he infants with the Fc gamma RIIa-Arg/Arg131 genotype were significantly le ss likely to be at risk for high-density falciparum infection, compared wit h infants with the Fc gamma RIIa-His/Arg131 genotype (adjusted odds ratio, 0.278; 95% confidence interval, 0.123-0.627; P=.0021). This finding support s the hypothesis.