Human Leukocyte Antigen (HLA)-F and -G Gene Polymorphisms and Haplotypes Are Associated with Malaria Susceptibility in the Beninese Toffin Children

Background: Little attention has been devoted to the role of the immunoregulatory HLA-E/-F/-G genes in malaria. We evaluated the entire HLA-E/-F/-G variability in Beninese children highly exposed to Plasmodium falciparum (P.f.) malaria. Methods: 154 unrelated children were followed-up for six months and evaluated for the presence and number of malaria episodes. HLA-E/-F/-G genes were genotyped using massively parallel sequencing. Anti P.f. antibodies were evaluated using ELISA. Results: Children carrying the G allele at HLA-F (-1499,rs183540921) showed increased P.f. asymptomatic/ symptomatic ratio, suggesting that these children experienced more asymptomatic P.f. episodes than symptomatic one. Children carrying HLA-G-UTR-03 haplotype exhibited increased risk for symptomatic P.f. episodes and showed lower IgG2 response against P.f. GLURP-R2 when compared to the non-carriers. No as-sociations were observed for the HLA-E gene. Conclusion: HLA-F associations may be related to the differential expression profiles of the encoded immuno-modulatory molecules, and the regulatory sites at the HLA-G 3'UTR may be associated to posttranscriptional regulation of HLA-G and to host humoral response against P.f.