A Non-Coding Fc Gamma Receptor Cis-Regulatory Variant within the 1q23 Gene Cluster Is Associated with <i>Plasmodium falciparum</i> Infection in Children Residing in Burkina Faso
2023
Jules Cretin | Mathieu Adjemout | Christelle Dieppois | Frederic Gallardo | Magali Torres | Zachary Merard | Serge Aimé Sawadogo | Christophe Picard | Pascal Rihet | Pascale Paul
Antibodies play a crucial role in activating protective immunity against malaria by interacting with Fc-gamma receptors (FcγRs). Genetic variations in genes encoding FcγRs can affect immune cell responses to the parasite. In this study, our aim was to investigate whether non-coding variants that regulate FcγR expression could influence the prevalence of <i>Plasmodium falciparum</i> infection. Through bioinformatics approaches, we selected expression quantitative trait loci (eQTL) for <i>FCGR2A, FCGR2B, FCGR2C, FCGR3A</i>, and <i>FCGR3B</i> genes encoding FcγRs (<i>FCGR</i>), in whole blood. We prioritized two regulatory variants, rs2099684 and rs1771575, located in open genomic regions. These variants were identified using RegVar, ImmuNexUT, and transcription factor annotations specific to immune cells. In addition to these, we genotyped the coding variants <i>FCGR2A</i>/rs1801274 and <i>FCGR2B</i>/rs1050501 in 234 individuals from a malaria-endemic area in Burkina Faso. We conducted age and family-based analyses to evaluate associations with the prevalence of malarial infection in both children and adults. The analysis revealed that the regulatory rs1771575-CC genotype was predicted to influence <i>FCGR2B/FCGR2C/FCGR3A</i> transcripts in immune cells and was the sole variant associated with a higher prevalence of malarial infection in children. In conclusion, this study identifies the rs1771575 cis-regulatory variant affecting several FcγRs in myeloid and neutrophil cells and associates it with the inter-individual capacity of children living in Burkina Faso to control malarial infection.
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