title: CD36 c.1264 T>G null mutation impairs acquisition of IgG antibodies to Plasmodium falciparum MSP1₁₉ antigen and is associated with higher malaria incidences in Tanzanian children.
abstract: Polymorphisms in genes that encode crucial signalling molecules have been proposed as factors that influence susceptibility to, and outcome of malaria. We studied the role of a mutation, c.1264 T>G, that causes CD36 deficiency on IgG responses to MSP-1₁₉ antigen and malaria incidence. Children were genotyped for the c.1264 T>G mutation at the beginning of the study using PCR-RFLP. IgG levels [optical density (OD) readings] and per cent seropositivity to MSP-1₁₉ were determined at baseline by ELISA. Children were followed for 12 months for acquisition of anti-MSP-1₁₉ IgG antibody and malaria incidence. We observed a significant increase in the production of anti-MSP-1₁₉ IgG antibody in normal and heterozygous children during the 12 months of follow-up, but not in homozygous mutants. Normal children had a significantly lower malaria incidence rate compared to other genotypes (χ² = 115.59; P < 0.01). We conclude that the presence of the c.1264 T>G mutation that leads to CD36 deficiency is closely associated with reduced IgG production and higher malaria incidence. It is most likely that deficiency of CD36 which is known to modulate dendritic cell function suppresses the production of protective IgG antibodies directed to Plasmodium falciparum MSP-1₁₉ antigen, which predisposes to the acquisition of clinical malaria in children.
authors: Department of Biochemistry and Molecular Biology, Kilimanjaro Christian Medical University College, Tumaini University, Moshi, Tanzania.
authors: D
authors: D
authors: Kajeguka
authors: C
authors: C
authors: Mwanziva
authors: M
authors: M
authors: Daou
authors: A
authors: A
authors: Ndaro
authors: S
authors: S
authors: Matondo
authors: E
authors: E
authors: Mbugi
authors: W
authors: W
authors: Dolmans
authors: J
authors: J
authors: Chilongola
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D018955:CD36 Antigens / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D015994:Incidence; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D013636:Tanzania / Q000453:epidemiology
chemical_list: D000913:Antibodies, Protozoan; D018955:CD36 Antigens; D007074:Immunoglobulin G; D020066:Merozoite Surface Protein 1; D004247:DNA