| Summary: | <p>Abstract</p> <p>Background</p> <p>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 <it>Plasmodium falciparum</it> parasite density levels.</p> <p>Methods</p> <p>Twelve regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of <it>FOXP3</it> (ss270137548, rs11091253), <it>IL10RA</it> (rs56356146, rs7925112), <it>IL10RB</it> (rs8178433, rs8178435, rs999788), <it>STAT6</it> (rs3024941, rs3024943, rs3024944) and <it>TNFRSF18</it> (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).</p> <p>Results</p> <p>The prevalence of <it>rs3024944CC</it> genotype of <it>STAT6</it> was significantly higher in the group of asymptomatic children compared to that of uncomplicated malaria (<it>P</it>=0.003). Similarly, the minor allele <it>rs3024944C</it> was more prevalent in the group of asymptomatic children (<it>P</it>=0.019). Two novel SNPs were observed including <it>-163T/G</it> (ss491228441) in <it>IL10RA</it> gene and <it>-163C/T</it> (ss491228440) in <it>TNFRSF18</it> gene. The genotype <it>ss491228441TT</it> and the minor allele <it>ss491228441G</it> of the <it>IL10RA</it> were more frequent in the group of asymptomatic children (<it>P</it>=0.006 and <it>P</it>=0.007, respectively). The genotype <it>rs11091253CT</it> of the <it>FOXP3</it> was associated with high parasite density levels. In addition, a new promoter <it>IL10RA</it> variant (ss491228441) contributes to shield against mild malaria.</p> <p>Conclusion</p> <p>The study indicated that the <it>STAT6</it> promoter polymorphism rs3024944 was associated with uncomplicated malaria, whereas the <it>FOXP3</it> promoter variant rs11091253 was associated with significant <it>P. falciparum</it> parasitaemia levels. These genetic data may contribute to the understanding of molecular mechanisms that regulate immune response to <it>P. falciparum</it> infections.</p>
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