Combined polymorphisms involving the IgG heavy chain and fc gamma receptors among Fulani and non-Fulani in Benin: Implications for the natural protection of young Fulani against plasmodium. Falciparum malaria infections.

A decreased susceptibility of Fulani populations to malaria infections has been shown in Africa. A previous longitudinal cohort study conducted in the Atacora region of northern Benin showed a high merozoite-phagocytosis capacity in young Fulani. Here, we explored the combined polymorphisms in the constant region of the IgG3 heavy chain (presence/absence of the G3m6 allotype) and in Fc gamma receptors (FcγRs) as potentially involved in the natural protection against malaria of young Fulani in Benin. An active malaria follow-up was conducted among individuals from Fulani, Bariba, Otamari and Gando ethnic groups living in sympatry in Atacora, over the full malaria transmission season. FcγRIIA 131R/H (rs1801274), FcγRIIC C/T (rs3933769) and FcγRIIIA 176F/V (rs396991) were determined using the TaqMan method; FcγRIIIB NA1/NA2 was assessed by polymerase chain reaction (PCR) using allele-specific primers and G3m6 using allotype by PCR-RFLP. Individual carriage of G3m6 (+) was associated with an increased risk of Pf malaria infection (logistic multivariate regression model (lmrm), IRR = 2.25, 95% CI = 1.06;4.74, P = 0.034). Combined haplotype G3m6 (+) - FcγRIIA 131H - FcγRIIC T - FcγRIIIA 176F - FcγRIIIB NA2 was also associated with an increased risk of Pf malaria infection (lmrm, IRR = 13.01, 95% CI = 1.69;99.76, P = 0.014). G3m6 (-), FcγRIIA 131R and FcγRIIIB NA1 were more prevalent in young Fulani (P = 0.002, P < 0.001 and P = 0.049, respectively), while no Fulani presented the combined G3m6 (+) - FcγRIIA 131H - FcγRIIC T - FcγRIIIA 176F - FcγRIIIB NA2 haplotype that was carried by a majority of infected children. Our results highlight the combined factors G3m6 - FcγR as potentially involved in the merozoite-phagocytosis capacity and in the natural protection of young Fulani individuals against P. falciparum malaria in Benin.