title: Association of FCgamma receptor IIA (CD32) polymorphism with malarial anemia and high-density parasitemia in infants and young children.
abstract: 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.
authors.affiliation: University of Pittsburgh/Kenya Medical Research Institute Laboratories of Parasitic and Viral Diseases, Kisumu, Kenya.
authors.forename: Collins
authors.initials: C
authors.lastname: Ouma
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Keller
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Opondo
authors.forename: Tom
authors.initials: T
authors.lastname: Were
authors.forename: Richard O
authors.initials: RO
authors.lastname: Otieno
authors.forename: Michael F
authors.initials: MF
authors.lastname: Otieno
authors.forename: Alloys S S
authors.initials: AS
authors.lastname: Orago
authors.forename: John M
authors.initials: JM
authors.lastname: Ong'Echa
authors.forename: John M
authors.initials: JM
authors.lastname: Vulule
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Perkins
mesh_terms: D000740:Anemia / Q000097:blood / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D015703:Antigens, CD / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000097:blood / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D008297:Male; D018512:Parasitemia / Q000097:blood / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D011110:Polymorphism, Genetic; D015995:Prevalence; D017452:Receptors, IgG / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG