In-vitro characterization of novel and functional regulatory SNPs in the promoter region of <it>IL2</it> and <it>IL2R alpha</it> in a Gabonese population

• Main Authors: Huang Xiangsheng (Author), Kühne Vera (Author), Kun Jürgen F J (Author), Soboslay Peter T (Author), Lell Bertrand (Author), TP Velavan (Author)
• Format: Book
• Published: BMC, 2012-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/1471-2350-13-117; 1471-2350
• Keywords: IL2; IL2R alpha; CD25; Polymorphism; Transfection; Regulatory T cells; Internal medicine; RC31-1245; Genetics; QH426-470
• Source: BMC Medical Genetics, Vol 13, Iss 1, p 117 (2012)

<p>Abstract</p> <p>Background</p> <p>The selection pressure imposed by the parasite has a functional consequence on the immune genes, leading to altered immune function in which regulatory T cells (Tregs) induced by parasites during infectious challenges modulate or thwart T effector cell mechanism.</p> <p>Methods</p> <p>We identified and investigated regulatory polymorphisms in the immune gene <it>IL2</it> and its receptor <it>IL2R alpha</it> (also known as <it>CD25</it>) in Gabonese individuals exposed to plentiful parasitic infections.</p> <p>Results</p> <p>We identified two reported variants each for <it>IL2</it> and its receptor <it>IL2R alpha gene loci.</it> Also identified were two novel variants, -83 /-84 <it>CT</it> deletions (<it>ss410961576)</it> for <it>IL2</it> and -409<it>C/T</it> (<it>ss410961577)</it> for <it>IL2R alpha</it>. We further validated all identified promoter variants for their allelic gene expression using transient transfection assays. Three promoter variants of the <it>IL2</it> locus revealed no significant expression of the reporter gene. The identified novel variant (<it>ss410961577C/T</it>) of the <it>IL2R alpha</it> revealed a significant higher expression of the reporter gene in comparison to the major allele (P<0.05). In addition, the <it>rs12722616C/T</it> variant of the <it>IL2R alpha</it> locus altered the transcription factor binding site TBP (TATA box binding protein) and C/EBP beta (CCAAT/enhancer binding protein beta) that are believed to regulate the Treg function.</p> <p>Conclusions</p> <p>The identification and validation of such regulatory polymorphisms in the immune genes may provide a basis for future studies on parasite susceptibility in a population where T cell functions are compromised.</p>