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

Abstract

Parasites remain competent invaders of host immunity. Their invasion strategies have proven to impact immunorelevant genes leading to diversity among gene families. We focussed on signal transducer and activator of transcription (STAT6) factor that plays a fundamental role in signal transduction and activation of transcription. Recent studies have highlighted the role of STAT6 variants in control of infection levels. We identified and investigated regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of the STAT6 gene in a group of Gabonese individuals exposed to a variety of parasitic infections. Three promoter variants were identified in 40 individual subjects. We further validated these promoter variants for their allelic gene expression using transient transfection assays. One promoter variant, rs3024944 (G/C), revealed an altered expression of the marker gene. The identification of function-altering SNPs in the promoter may facilitate studying parasite susceptibility in association studies

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

“…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.…”

“…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.…”

“…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.…”

Regulatory T Cells and Parasites

“…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.…”

“…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.…”