Generic Portal

TY - JOUR

T1 - Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso

AU - Natama, Hamatandi Magloire

AU - Rovira-Vallbona, Eduard

AU - Krit, Meryam

AU - Guetens, Pieter

AU - Sorgho, Hermann

AU - Somé, M. Athanase

AU - Traoré-Coulibaly, Maminata

AU - Valéa, Innocent

AU - Mens, Petra F.

AU - Schallig, Henk D. F. H.

AU - Berkvens, Dirk

AU - Kestens, Luc

AU - Tinto, Halidou

AU - Rosanas-Urgell, Anna

N1 - Funding Information: This work was supported by the Belgium Directorate General for Development Cooperation (DGD, Grant number FA3-III ITM-CRUN) under the Framework Agreement Program between ITM and CRUN (2014-2016) and COSMIC project funded by European Union Seventh Framework Programme (FP7/2002-2016) under grant agreement no 305662-COSMIC. Funding Information: We sincerely thank mothers and their offspring for participating into this study. We acknowledge the research teams at the Clinical Research Unit of Nanoro (CRUN) in Burkina Faso and at the Malariology Unit, Institute of Tropical Medicine (ITM, Belgium) for this successful collaborative research project. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

KW - Cytokines

KW - Immunogenetic variants

KW - Innate immunity

KW - Malaria

KW - Plasmodium falciparum

UR - http://www.scopus.com/inward/record.url?scp=85100903513&partnerID=8YFLogxK

U2 - 10.1186/s12936-021-03628-y

DO - 10.1186/s12936-021-03628-y

M3 - Article

C2 - 33593344

VL - 20

JO - Malaria journal

JF - Malaria journal

SN - 1475-2875

IS - 1

M1 - 94

ER -