title: Fcgamma receptor IIA and IIIB polymorphisms are associated with susceptibility to cerebral malaria.
abstract: 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.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Omi
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.forename: Jintana
authors.initials: J
authors.lastname: Patarapotikul
authors.forename: Hathairad
authors.initials: H
authors.lastname: Hananantachai
authors.forename: Izumi
authors.initials: I
authors.lastname: Naka
authors.forename: Sornchai
authors.initials: S
authors.lastname: Looareesuwan
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D058851:GPI-Linked Proteins; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016779:Malaria, Cerebral / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D013785:Thailand
chemical_list: D015703:Antigens, CD; C428200:FCGR3B protein, human; C080568:Fc gamma receptor IIA; D058851:GPI-Linked Proteins; D017452:Receptors, IgG