Association of HLA-G 3'UTR polymorphisms with response to malaria infection: a first insight

Malaria represents one of the most important causes of mortality and morbidity in Africa. Variability in clinical presentation is partly due to host genetic polymorphisms. Among them, human leukocyte antigen (HLA) class I and class II alleles may be responsible for malaria susceptibility; however less is known about the possible role of non classical HLA molecules. Among them, HLA-G is a tolerogenic molecule with immunomodulatory properties, which differs from classical HLA class I molecules by its lower genetic diversity, tissue expression and function. Although primarily associated with maternal-fetal tolerance, HLA-G is now known to be involved in a wide range of physiopathological conditions, such as tumor, autoimmunity, transplantation, inflammation and viral infection by suppressing the function of various immune cells. In this work, we present the first evidence of an association between HLA-G 3'UTR polymorphisms and malaria infection. More precisely, we showed that HLA-G polymorphisms are associated with asymptomatic infection through two parasitological phenotypes, the intensity of Plasmodium falciparum infection and the mean level of parasite density. The allele+3187G and its haplotype (UTR-1, 14bp-Del/3001C/3003T/3010G/3035C/3052C/3142C/3187G/3196C) was associated with lower level of infection under a dominant model, and the haplotype UTR-3 (Del/3001C/3003T/3010C/3035C/3152C/3142G/3187A/3196C) was associated with high levels of infection under a recessive model. In conclusion, although further investigations are on the way to better address the possible involvement of the HLA-G molecule in the control of P. falciparum infection, this work presents the first evidence of an association between HLA-G polymorphisms and malaria infection. Further investigations are on the way to take into account the particularities of African populations.