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IFNG rs1861494 polymorphism is associated with IBD disease severity and functional changes in both IFNG methylation and protein secretion.

ABSTRACT: Mucosal expression of interferon (IFN)-? plays a pivotal role in the pathogenesis of inflammatory bowel disease (IBD) and IBD risk regions flank IFNG. The conserved IFNG rs1861494 T/C introduces a new CpG methylation site, is associated with disease severity and lack of therapeutic response in other infectious and immune-mediated disorders, and is in linkage disequilibrium with a ulcerative colitis (UC) disease severity region. It seems likely that CpG-altering single nucleotide polymorphisms modify methylation and gene expression. This study evaluated the association between rs1861494 and clinical, serologic, and methylation patterns in patients with IBD.Peripheral T cells of UC and Crohn's disease (CD) patients were genotyped for rs1861494 and analyzed for allele-specific and IFNG promoter methylation. Serum antineutrophil cytoplasmic autoantibodies and IFN-? secretion were measured by enzyme-linked immunosorbent assay and nucleoprotein complex formation by electrophoretic mobility shift assay.IFNG rs1861494 T allele carriage in patients with IBD was associated with enhanced secretion of IFN-?. T allele carriage was associated in UC with high levels of antineutrophil cytoplasmic autoantibodies and faster progression to colectomy. In CD, it was associated with complicated disease involving a stricturing/penetrating phenotype. Likewise, IFNG rs1861494 displayed genotype-specific modulation of DNA methylation and transcription factor complex formation.This study reports the first association of IFNG rs1861494 T allele with enhanced IFN-? secretion and known IBD clinical parameters indicative of more aggressive disease and serological markers associated with treatment resistance to anti-tumor necrosis factor therapy in patients with IBD. These data may be useful prognostically as predictors of early response to anti-tumor necrosis factor therapy to identify patients with IBD for improved personalized therapeutics.

SUBMITTER: Gonsky R

PROVIDER: S-EPMC4327845 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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IFNG rs1861494 polymorphism is associated with IBD disease severity and functional changes in both IFNG methylation and protein secretion.

Gonsky Rivkah R Deem Richard L RL Landers Carol J CJ Haritunians Talin T Yang Shaohong S Targan Stephan R SR

Inflammatory bowel diseases 20141001 10

<h4>Background</h4>Mucosal expression of interferon (IFN)-γ plays a pivotal role in the pathogenesis of inflammatory bowel disease (IBD) and IBD risk regions flank IFNG. The conserved IFNG rs1861494 T/C introduces a new CpG methylation site, is associated with disease severity and lack of therapeutic response in other infectious and immune-mediated disorders, and is in linkage disequilibrium with a ulcerative colitis (UC) disease severity region. It seems likely that CpG-altering single nucleoti ...[more]

PMID: 25171510

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Project description:Objectives Interferon-gamma (IFNg) is an immune-regulatory cytokine with a role in host responses to periodontitis. Genetic factors have been reported to modify the corresponding protein expression. The objective of this study was to evaluate the association and role of IFNg polymorphisms, such as IFNg +874 A/T, and the susceptibility to periodontitis.Materials and methods A total of 100 unrelated subjects were included in the present study. Genomic deoxyribonucleic acid (DNA) was obtained from peripheral blood of 43 patients with mild periodontitis and 57 patients with severe periodontitis. The determined clinical parameters of periodontitis included probing depth, clinical attachment loss, and papilla bleeding index. The oral hygiene indicators were also assessed. The level of IFNg was determined from the gingival crevicular fluid by enzyme-linked immunosorbent assay technique. The IFNg +874 A/T polymorphisms were analyzed from peripheral blood by the method of restriction fragment length polymorphism-polymerase chain reaction.Statistical analysis Statistical analysis of the results was conducted using chi-squared testing for categorical data. Independent t-tests and Mann-Whitney U tests were used for numeric data. Kruskal-Wallis testing was used to compare genotypes concerning for IFNg +874 A/T polymorphism. A p-value < 0.05 was assumed for statistical significance.Results Analysis of the IFNg +874 A/T polymorphism showed no significant differences with the level of IFNg. No significant differences were observed either in IFNg +874 A/T polymorphism between the subjects with mild periodontitis and those with severe periodontitis (p > 0.05). The subjects with severe periodontitis showed marginally but not significantly higher levels of IFNg compared with subjects with mild periodontitis (p > 0.05).Conclusion The polymorphism of IFNg +874 A/T was not associated with the level of IFNg nor with the risk of periodontitis in this study.

Dataset Information

IFNG rs1861494 polymorphism is associated with IBD disease severity and functional changes in both IFNG methylation and protein secretion.

Publications

IFNG rs1861494 polymorphism is associated with IBD disease severity and functional changes in both IFNG methylation and protein secretion.

Similar Datasets

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