Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso

• Published in: Malaria Journal
• Main Authors: Hamatandi Magloire Natama, Eduard Rovira-Vallbona, Meryam Krit, Pieter Guetens, Hermann Sorgho, M. Athanase Somé, Maminata Traoré-Coulibaly, Innocent Valéa, Petra F. Mens, Henk D. F. H. Schallig, Dirk Berkvens, Luc Kestens, Halidou Tinto, Anna Rosanas-Urgell
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2021
• Subjects: Malaria; Plasmodium falciparum; Immunogenetic variants; Cytokines; Innate immunity; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-021-03628-y; https://doaj.org/article/28641e0d45224781aa5692bfdde868b9

Abstract Background Genetic 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. Methods Seventeen 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). Results Genetic variants in IL-1β (rs1143634) and FcγRIIA/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 FcγRIIA/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 Fcγ receptors on effector immune cells. Conclusions These 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.