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Background  Regulatory T cells (Tregs) are a subset of T cells that play an important role in modulating T effector responses during infectious challenges. The aim of this study was to evaluate possible associations between regulatory gene polymorphisms and the risk of uncomplicated malaria and the control of  Plasmodium falciparum  parasite density levels.    Methods  Twelve regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of  FOXP3  (ss270137548, rs11091253),  IL10RA  (rs56356146, rs7925112),  IL10RB  (rs8178433, rs8178435, rs999788),  STAT6  (rs3024941, rs3024943, rs3024944) and  TNFRSF18  (ss2080581728, rs3753344) were genotyped in a cohort of Congolese children. Studied subjects were followed up (passively) during one year. The children who experienced one or several clinical episodes were genotyped as “uncomplicated malaria” group (n=179) and those children who did not experience any episode were genotyped as “asymptomatic children” group (n=138).    Results  The prevalence of  rs3024944CC  genotype of  STAT6  was significantly higher in the group of asymptomatic children compared to that of uncomplicated malaria ( P =0.003). Similarly, the minor allele  rs3024944C  was more prevalent in the group of asymptomatic children ( P =0.019). Two novel SNPs were observed including  -163T/G  (ss491228441) in  IL10RA  gene and  -163C/T  (ss491228440) in  TNFRSF18  gene. The genotype  ss491228441TT  and the minor allele  ss491228441G  of the  IL10RA  were more frequent in the group of asymptomatic children ( P =0.006 and  P =0.007, respectively). The genotype  rs11091253CT  of the  FOXP3  was associated with high parasite density levels. In addition, a new promoter  IL10RA  variant (ss491228441) contributes to shield against mild malaria.    Conclusion  The study indicated that the  STAT6  promoter polymorphism rs3024944 was associated with uncomplicated malaria, whereas the  FOXP3  promoter variant rs11091253 was associated with significant  P. falciparum  parasitaemia levels. These genetic data may contribute to the understanding of molecular mechanisms that regulate immune response to  P. falciparum  infections.

malaria journal

Genetic evidence of regulatory gene variants of the STAT6, IL10R and FOXP3 locus as a susceptibility factor in uncomplicated malaria and parasitaemia in Congolese children