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

Abstract

BackgroundRegulatory 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.MethodsTwelve 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).ResultsThe 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.ConclusionThe 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.

Beyond genome-wide scan: Association of a cis-regulatory NCR3 variant with mild malaria in a population living in the Republic of Congo

“…The study subjects have resided in Kinsana, Mbouono and Ngoko, three suburban areas close to each other and located in Makélékélé, one of the seven districts of Brazzaville (Congo) [ 37 ]. Three hundred and seventeen individuals were recruited between April and June 2010 and followed up during one year.…”

Adipokines: biological functions and metabolically healthy obese profile

“…IL-10Rβ is believed to contribute only to the signaling process. 80 The binding of IL-10 to the receptor results in activation of the tyrosine kinases JAK1 and Tyk2, associated with the receptor, resulting in STAT3 phosphorylation and induction of STAT3-dependent genes, including SOCS3. 81,82 High levels of IL-10 transcripts block the production of inflammatory mediators, such as TNF, IL-6, IL-1β, and chemokines, and increase such anti-inflammatory cytokines as IL-1Rα.…”

Co-infection of human parvovirus B19 with Plasmodium falciparum contributes to malaria disease severity in Gabonese patients

“…Malaria is one of the major causes of morbidity and mortality in tropical and sub-tropical countries and is caused by the protozoan parasites of the genus Plasmodium while Plasmodium falciparum ( P. falciparum ) being the most virulent species [1]. …”