Dataset Information

CISH promoter polymorphism effects on T cell cytokine receptor signaling and type 1 diabetes susceptibility.

ABSTRACT: BACKGROUND:Impaired regulatory T cell immunity plays a central role in the development of type 1 diabetes (T1D). Interleukin-2 receptor (IL-2R) signaling is essential for regulatory T cells (TREG), and cytokine-inducible SH2-containing protein (CIS) regulates IL-2R signaling as a feedback inhibitor. Previous studies identified association of CISH promoter region single nucleotide polymorphisms (SNPs) with susceptibility to infectious diseases. METHODS:Here we analyzed allele frequencies of three CISH SNPs (i.e., rs809451, rs414171, rs2239751) in a study of T1D patients (n?=?260, onset age ?10 years). Minor allele frequencies were compared to a control cohort of the 1000 Genomes Project. Assigned haplotypes were determined for effects on T1D manifestation and severity. Finally, the CISH haplotype influence on cytokine signaling and function was explored in T cells from healthy donors. RESULTS:We detected similar minor allele frequencies between T1D patients and the control cohort. T1D onset age, residual serum C-peptide level, and insulin requirement were comparable between different haplotypes. Only minor differences between the haplotypes were found for in vitro cytokine (i.e., IL-2, IL-7)-induced CIS mRNA expression. STAT5 phosphorylation was induced by IL-2 or IL-7, but no differences were found between the haplotypes. TREG purified from healthy donors with the two most common haplotypes showed similar capacity to inhibit heterologous effector T cells. CONCLUSIONS:This study provides no evidence for an association of CISH promoter SNPs with susceptibility to T1D or severity of disease. In contrast to previous studies, no influence of different haplotypes on CIS mRNA expression or T cell-mediated functions was found.

SUBMITTER: Seyfarth J

PROVIDER: S-EPMC5801137 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CISH promoter polymorphism effects on T cell cytokine receptor signaling and type 1 diabetes susceptibility.

Seyfarth Julia J Ahlert Heinz H Rosenbauer Joachim J Baechle Christina C Roden Michael M Holl Reinhard W RW Mayatepek Ertan E Meissner Thomas T Jacobsen Marc M

Molecular and cellular pediatrics 20180206 1

<h4>Background</h4>Impaired regulatory T cell immunity plays a central role in the development of type 1 diabetes (T1D). Interleukin-2 receptor (IL-2R) signaling is essential for regulatory T cells (T<sub>REG</sub>), and cytokine-inducible SH2-containing protein (CIS) regulates IL-2R signaling as a feedback inhibitor. Previous studies identified association of CISH promoter region single nucleotide polymorphisms (SNPs) with susceptibility to infectious diseases.<h4>Methods</h4>Here we analyzed a ...[more]

PMID: 29411179

Similar Datasets

Project description:Our previous studies have implicated genes mainly involved in the activity of pancreatic ? cells in type 2 diabetes (T2D) susceptibility in the North Indian population. Recent literature on the role of SIRT1 as a potential master switch modulating insulin secretion and regulating gene expression in pancreatic ? cells has warranted an evaluation of SIRT1 promoter region polymorphisms in the North Indian population, which is the main focus of the present study. 1542 samples (692 T2D patients and 850 controls) were sequenced for the 1.46 kb region upstream the translation start site of the SIRT1 gene. We performed a functional characterization of the SIRT1 promoter region polymorphisms using luciferase assay and observed a single-nucleotide polymorphism (SNP), rs12778366, in association with SIRT1 expression. We propose that TT, the high-expressing genotype of SNP rs12778366 in the SIRT1 promoter region and present in >80% of the North Indian population, was favored under conditions of feast-famine cycles in evolution, which has turned out to be a cause of concern in the present sedentary lifestyle under ad libitum conditions. Case-control association analysis did not implicate rs12778366 in T2DM per se in the studied population. However, our earlier reported risk genotype combinations of mt-ND3, PGC1?, and UCP2-866, when compared with the protective genotype combinations, in the background of the high-expressing TT genotype of SIRT1 SNP rs12778366, showed a very high additive risk [corrected odd ratio (OR)?=?8.91; p?=?6.5×10(-11)]. The risk level was considerably low in the genotype backgrounds of TX (OR?=?6.68; p?=?2.71×10(-12)) and CX (OR?=?3.74; p?=?4.0×10(-3)). In addition, we screened other reported T2D-associated polymorphisms: PIK3R1 rs3730089, IRS1 rs1801278, and PPP1R3 rs1799999, which did not show any significant association in North Indian population. The present paper emphasizes the importance of gene interactions in the biological pathways of T2D, a complex lifestyle disease.

Dataset Information

CISH promoter polymorphism effects on T cell cytokine receptor signaling and type 1 diabetes susceptibility.

Publications

CISH promoter polymorphism effects on T cell cytokine receptor signaling and type 1 diabetes susceptibility.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets