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

<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 polym...

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Main Authors: Koukouikila-Koussounda Felix, Ntoumi Francine, Ndounga Mathieu, Tong Hoang V, Abena Ange-Antoine, Velavan Thirumalaisamy P
Format: Article
Language:English
Published: BMC 2013-01-01
Series:Malaria Journal
Subjects:
Online Access:http://www.malariajournal.com/content/12/1/9
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author Koukouikila-Koussounda Felix
Ntoumi Francine
Ndounga Mathieu
Tong Hoang V
Abena Ange-Antoine
Velavan Thirumalaisamy P
author_facet Koukouikila-Koussounda Felix
Ntoumi Francine
Ndounga Mathieu
Tong Hoang V
Abena Ange-Antoine
Velavan Thirumalaisamy P
author_sort Koukouikila-Koussounda Felix
collection DOAJ
description <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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spelling doaj.art-6000f2fc56f247df9a95a0ca85c957f52022-12-22T01:17:27ZengBMCMalaria Journal1475-28752013-01-01121910.1186/1475-2875-12-9Genetic evidence of regulatory gene variants of the <it>STAT6, IL10R</it> and <it>FOXP3</it> locus as a susceptibility factor in uncomplicated malaria and parasitaemia in Congolese childrenKoukouikila-Koussounda FelixNtoumi FrancineNdounga MathieuTong Hoang VAbena Ange-AntoineVelavan Thirumalaisamy P<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>http://www.malariajournal.com/content/12/1/9<it>Plasmodium falciparum</it>Tregs<it>FOXP3</it><it>IL10RA</it><it>STAT6</it>
spellingShingle Koukouikila-Koussounda Felix
Ntoumi Francine
Ndounga Mathieu
Tong Hoang V
Abena Ange-Antoine
Velavan Thirumalaisamy P
Genetic evidence of regulatory gene variants of the <it>STAT6, IL10R</it> and <it>FOXP3</it> locus as a susceptibility factor in uncomplicated malaria and parasitaemia in Congolese children
Malaria Journal
<it>Plasmodium falciparum</it>
Tregs
<it>FOXP3</it>
<it>IL10RA</it>
<it>STAT6</it>
title Genetic evidence of regulatory gene variants of the <it>STAT6, IL10R</it> and <it>FOXP3</it> locus as a susceptibility factor in uncomplicated malaria and parasitaemia in Congolese children
title_full Genetic evidence of regulatory gene variants of the <it>STAT6, IL10R</it> and <it>FOXP3</it> locus as a susceptibility factor in uncomplicated malaria and parasitaemia in Congolese children
title_fullStr Genetic evidence of regulatory gene variants of the <it>STAT6, IL10R</it> and <it>FOXP3</it> locus as a susceptibility factor in uncomplicated malaria and parasitaemia in Congolese children
title_full_unstemmed Genetic evidence of regulatory gene variants of the <it>STAT6, IL10R</it> and <it>FOXP3</it> locus as a susceptibility factor in uncomplicated malaria and parasitaemia in Congolese children
title_short Genetic evidence of regulatory gene variants of the <it>STAT6, IL10R</it> and <it>FOXP3</it> locus as a susceptibility factor in uncomplicated malaria and parasitaemia in Congolese children
title_sort genetic evidence of regulatory gene variants of the it stat6 il10r it and it foxp3 it locus as a susceptibility factor in uncomplicated malaria and parasitaemia in congolese children
topic <it>Plasmodium falciparum</it>
Tregs
<it>FOXP3</it>
<it>IL10RA</it>
<it>STAT6</it>
url http://www.malariajournal.com/content/12/1/9
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