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

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

Inflammatory bowel diseases (2014-08-30)
Rivkah Gonsky, Richard L Deem, Carol J Landers, Talin Haritunians, Shaohong Yang, Stephan R Targan
ABSTRACT

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 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-γ 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-γ. 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-γ 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2-Propanol, BioReagent, for molecular biology, ≥99.5%
Sigma-Aldrich
2-Propanol, suitable for HPLC, 99.9%
Sigma-Aldrich
2-Propanol, ACS reagent, ≥99.5%
Sigma-Aldrich
2-Propanol, anhydrous, 99.5%
Sigma-Aldrich
Isopropyl alcohol, ≥99.7%, FCC, FG
Sigma-Aldrich
Isopropyl alcohol, meets USP testing specifications
Sigma-Aldrich
2-Propanol, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)
Sigma-Aldrich
2-Propanol, HPLC Plus, for HPLC, GC, and residue analysis, 99.9%
Sigma-Aldrich
2-Propanol, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide phosphate hydrate
Sigma-Aldrich
2-Propanol, Laboratory Reagent, ≥99.5%
Sigma-Aldrich
2-Propanol, puriss. p.a., ACS reagent, ≥99.8% (GC)
Supelco
2-Propanol, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
2-Propanol, analytical standard
Sigma-Aldrich
2-Propanol, electronic grade, 99.999% trace metals basis
Sigma-Aldrich
2-Propanol, puriss., meets analytical specification of Ph. Eur., BP, USP, ≥99.5% (GC)
USP
2-Propanol, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
2-Propanol, suitable for HPLC, 99.5%
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide phosphate sodium salt, pkg of 5 mg (per vial)
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide phosphate sodium salt, pkg of 10 mg (per vial)