Fcgamma receptor IIa (CD32) polymorphism is associated with protection of infants 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 monocytes via the Fcgamma receptor II (FcgammaRII). A single amino acid substitution at position 131 in FcgammaRIIa is critical in the binding of human IgG subclasses. The hypothesis that the FcgammaRIIa-Arg/Arg131 genotype, 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 Kenya were selected for an unmatched case-control study. Results showed that the infants with the FcgammaRIIa-Arg/Arg131 genotype were significantly less likely to be at risk for high-density falciparum infection, compared with infants with the FcgammaRIIa-His/Arg131 genotype (adjusted odds ratio, 0.278; 95% confidence interval, 0.123-0.627; P=.0021). This finding supports the hypothesis.
Shi
Y P
YP
Division of Parasitic Diseases, National Centers for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. shi_yaping@hotmail.com
Nahlen
B L
BL
Kariuki
S
S
Urdahl
K B
KB
McElroy
P D
PD
Roberts
J M
JM
Lal
A A
AA
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D007630:Kenya; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D010963:Plasmodium falciparum; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D017452:Receptors, IgG / Q000235:genetics*; D013329:Structure-Activity Relationship
D007074:Immunoglobulin G; D017452:Receptors, IgG; D001120:Arginine