Fcgamma receptor IIA and IIIB polymorphisms are associated with susceptibility to cerebral malaria.

Human FcgammaRIIA and FcgammaRIIIB exhibit genetic polymorphisms, FcgammaRIIA-131H/R and FcgammaRIIIB-NA1/NA2, coding for different capacities for IgG binding and phagocytosis. Recently, FcgammaRIIA-131R was reported to be associated with protection against high-density Plasmodium falciparum infection in Kenya. Furthermore, FcgammaRIIIB-NA1/NA2 polymorphism was shown to influence FcgammaRIIA function in an allele-specific manner. In this study, we examined a possible association of FcgammaRIIA-131H/R and FcgammaRIIIB-NA1/NA2 polymorphisms with malaria severity in 107 cerebral malaria patients, 157 non-cerebral severe malaria patients, and 202 mild malaria controls living in northwest Thailand. This study reveals that, with the FcgammaRIIIB-NA2 allele, the FcgammaRIIA-131H/H genotype is associated with susceptibility to cerebral malaria (OR 1.85, 95% CI 1.14-3.01; P=0.012), although these polymorphisms are not individually involved in the disease severity. Our results suggest that FcgammaRIIA-131H/R and FcgammaRIIIB-NA1/NA2 polymorphisms have an interactive effect on host defense against malaria infection.