Molecular characterization of regulatory polymorphisms in the promoter region of the STAT6 gene in a Gabonese population

Velavan, Thirumalaisamy P.; Bechlars, Silke; Tomiuk, Jürgen; Kremsner, Peter G.; Kun, Jürgen F. J.

doi:10.1590/s0074-02762011000100011

Cited by 7 publications

(7 citation statements)

References 18 publications

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“…Earlier studies have identified some regulatory SNPs on the promoter loci of these five genes from 40 unrelated Gabonese individuals who had earlier infection episodes with various parasites, including P. falciparum [14,19-21]. These SNPs were then validated for their allelic gene expression using transient transfection assays.…”

Section: Discussionmentioning

confidence: 99%

“…Some of the identified were already pre-described, while others were newly discovered. All the SNPs selected for the current investigation were found to alter expression of their respective gene [14,19-21]. Therefore any possible correlations of these SNP variants with resistance or susceptibility to mild malaria attacks and/or the control of P. falciparum infection levels were evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…These identified SNPs were further validated for their allelic gene expression using transient transfection assays [14,19-21]. Against this background, in the present study, the possible relationship between the reported SNP variants and risk of having uncomplicated P. falciparum malaria was investigated.…”

Section: Introductionmentioning

confidence: 99%

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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

Koukouikila-Koussounda

Ntoumi

Ndounga

et al. 2013

Malar J

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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

Koukouikila-Koussounda

Ntoumi

Ndounga

et al. 2013

Malar J

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“…The crippling effect of host immunity on onset of an infection is due to the fact that parasites induce Tregs that in turn suppress antiparasite effector cells [4]. The Tregs are a subset of T cells that function to control immune responses.…”

Section: Regulatory T Cellsmentioning

confidence: 99%

“…The single-nucleotide polymorphisms (SNPs) in the promoter region of the genes such as STAT6 , Foxp3 , and TNFRSF18 were well characterized for their functional role [4, 10, 83]. One gene of interest that plays a key role in the function of Tregs is the IL-10 gene locus.…”

Section: Regulatory Gene Polymorphismsmentioning

confidence: 99%

Regulatory T Cells and Parasites

Velavan

Ojurongbe

2011

BioMed Research International

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Human host encounters a wide array of parasites; however, the crucial aspect is the failure of the host immune system to clear these parasites despite antigen recognition. In the recent past, a new immunological concept has emerged, which provides a framework to better understand several aspects of host susceptibility to parasitic infection. It is widely believed that parasites are able to modulate the magnitude of effector responses by inducing regulatory T cell (Tregs) population and several studies have investigated whether this cell population plays a role in balancing protective immunity and pathogenesis during parasite infection. This review discusses the several mechanism of Treg-mediated immunosuppression in the human host and focuses on the functional role of Tregs and regulatory gene polymorphisms in infectious diseases.

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FOXO3A regulatory polymorphism and susceptibility to severe malaria in Gabonese children

2014

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The clinical course of malaria varies between affected individuals and host genetic factors have been shown to influence the outcome of malaria. The role of FOXO3-driven pathway in modulating inflammatory responses, including mediation of distinct functions of regulatory T effector cell populations (Tregs) by the transcription factor FOXO3, has recently been recognized. We aimed to study possible associations of a non-coding polymorphism in intron 2 of the FOXO3A gene (rs12212067T>G) that was shown earlier to modulate the FOXO3 expression and to be associated with the prognosis of distinct inflammatory and infectious diseases. The FOXO3A polymorphism rs12212067T>G was genotyped by direct sequencing in a group of Gabonese children with confirmed Plasmodium falciparum malaria. Severe cases of malaria were compared with asymptomatic/mild cases. The FOXO3A variant rs12212067T>G was associated with the phenotype of severe malaria, but not with asymptomatic/mild malaria (allelic model: OR = 1.54, 95 % CI = 1.15-2.05, P = 0.0028; dominant model: OR = 1.94, 95 % CI = 1.36-2.77, P = 0.0002). The FOXO3A variant rs12212067T>G is associated with increased inflammatory responses to Plasmodium falciparum malaria, indicating a role of the FOXO3-dependent pathway in malaria.

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Molecular characterization of regulatory polymorphisms in the promoter region of the STAT6 gene in a Gabonese population

Cited by 7 publications

References 18 publications

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

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

Regulatory T Cells and Parasites

FOXO3A regulatory polymorphism and susceptibility to severe malaria in Gabonese children

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