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Genetic variation in the immune system and malaria susceptibility in infants

Journal Contribution - e-publication

Subtitle:a nested case-control study in Nanoro, Burkina Faso
BackgroundGenetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso.MethodsSeventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case-control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex).ResultsGenetic variants in IL-1 beta (rs1143634) and Fc gamma RIIA/CD32 (rs1801274)-both in allelic, dominant and co-dominant models-were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in Fc gamma RIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P=0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fc gamma receptors on effector immune cells.ConclusionsThese findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators.
Journal: Malaria journal
ISSN: 1475-2875
Volume: 20
Publication year:2021
Keywords:A1 Journal article