Bakground: The interaction between antibodies and Fcy receptors (FcyRs) plays a critical role in regulating immune responses to Plasmodium falciparum. Polymorphisms in genes encoding FcyRs influence the host's capacity to control parasite infection. The study investigates whether noncoding variants influencing FcyR expression are associated with antimalarial immunization and infection traits.
Methodes: We utilized qQTL databases and functional annotations to identify noncoding variants, specifically rs1771575, rs2099684 and rs6700241, within the FCGR gene cluster. In addition, we examined the coding variants rs1801274 (p.His167Arg) and rs1050501 (p.Ile231Thr) which affect the affinity of FcYRlla and FcyRIIb for IgG. These variants were genotyped in 163 individuals from Burkinabe families. Family-based linear mixed regression and Quantitative Transmission Disequilibrium Tests (QTDT) analyses were performed to assess associations with IgG levels and malaria infection accounting for relevant covariates.
Results: Linear models identified rs1771575 as associated with total IgG levels, while both rs1771575 and rs1801274 were linked to IgG2 and rs1050501 to IgG1 levels. A haplotype combining rs2099684 and rs6700241 was positively associated with IgG1. The rs1771575-CC ans rs1050501-TT genotypes correlated with higher infection levels in children. QTDT models confirmed the association of rs1771575 with IgGE and infection in children.
Conclusion: Our findings suggest that the intergenic variant of rs1771575 serves as an independent marker fo IgG levels and blood infection in children. This highlights the interplay between regulatory variants and coding mutations in FCGR, which may influence immune function and antibody production. These results underscore the potential for personalized strategies to monitor humoral responses in malaria-endemic regions.

FCGR expression quantitative trait locus; FCGR polymorphism; Plasmodium falciparum immunization; Fc gamma receptors; malaria.