Protective immunity against Plasmodium falciparum is partially mediated through binding of
malaria-specific
IgG antibodies to Fcgamma receptors. Polymorphic variability in Fcgamma RIIa (H/R-131) is associated with differential binding of
IgG subtypes and
malaria disease outcomes. However, the role of Fcgamma RIIa-131 variability in conditioning susceptibility to severe malarial
anemia, the primary manifestation of severe
malaria in holoendemic P. falciparum transmission areas, is largely undefined. Thus, Fcgamma RIIa-H131R polymorphism was investigated in 493 children who came to a hospital with
acute malaria. Variation in Fcgamma RIIa-131 was not significantly associated with severe malarial
anemia (
hemoglobin [Hb] < 6.0 g/dL) or
malaria anemia (Hb < 8.0 g/dL). However, relative to the heterozygous genotype, homozygotes for the R131 alleles were protected against high-density
parasitemia (>or= 10,000 parasites/microL; odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.37-0.92, P = 0.02), while homozygotes for the H131 alleles were mildly protective (OR = 0.71, 95% CI = 0.45-1.13, P = 0.14). Additional multivariate analyses showed that
infection with human immunodeficiency virus type 1 did not influence the associations between FcgammaRIIa-H131R polymorphism and
malaria disease outcomes. Genotypic results presented here parallel data illustrating that parasite density is unrelated to the severity of
anemia in children with
acute malaria. Thus, although homozygosity for the R131 allele protects against high-density
parasitemia, FcgammaRIIa-131 polymorphism does not protect against
malaria anemia.