Association of T Helper 1 Cytokine Gene Single Nucleotide Polymorphisms with Ulcerative Colitis and Crohn’s Disease

Abstract

Background: Inflammatory bowel disease (IBD) mostly comprised of Crohn’s disease (CD) and ulcerative colitis (UC) is a condition arising from the combined effects of genetic, environmental, and immunological factors. IBD is associated with inflammation and altered cytokine profile. Objective: This study was aimed at assessing the association between T helper type 1 (Th1) cytokine polymorphisms (interferon gamma [IFN-γ] +874 A/T, interleukin-12 [IL-12] –1188 A/C, IL-2 –330 G/T, IL-2 +166 G/T) and susceptibility to and clinical features of IBD. Methods: The study population was composed of 75 IBD patients (40 CD patients and 35 UC patients) and 140 healthy controls. Genotyping was performed using polymerase chain reaction with sequence-specific primers. Results: The A allele of IFN-γ +874 polymorphism was overrepresented in the whole population of patients with IBD (OR 1.63; 95% CI 1.08–2.47; p = 0.020) and as well in the subpopulation of patients with CD (OR 2.14; 95% CI 1.26–3.63; p = 0.004), but not in UC. Multiple pairwise comparisons indicated that genotypes of single nucleotide polymorphisms (SNPs) within the IL-2 and IFN-γ genes are correlated with IBD, CD, and UC, while neither allele nor genotype frequency of th1 IL-12 –1188 polymorphism was associated with IBD, CD, or UC. Haplotype analysis also revealed that the presence of IL-2 –330/+166 TG haplotype versus the remaining haplotypes (GG, TT, and GT) is a protective factor against IBD (OR 0.62; p = 0.046). Conclusions: The present study reports (for the first time) significant associations between SNPs within the IFN-γ and IL-2 genes and IBD.

Role of interleukins 12B and 17A genetic variation in house dust mites allergy

“…These results indicate that the IL-12 p40 3′UTR +1188 A/C polymorphism is associated with susceptibility to dust mites allergy in Egyptian patients as presented in a study where the A allele was decreased in atopic dermatitis [8] and other studies showed an increase in C alleles among asthmatic patients [53] and allergic rhinitis [54]. The CC genotype carriers were significantly overrepresented among autoimmune diseases as in ulcerative colitis, Crohn's disease [52], and lepromatous leprosy patients [55].…”

“…Recent studies have suggested that certain molecules' SNPs affect their level of expression or function [52]. Numerous molecules, including cytokines, are now believed to be associated with the pathogenesis of immune-mediated diseases, and some of these molecules' gene polymorphisms are considered candidates as genetic factors in these diseases.…”

Process Design of the Antioxidant Shuidouchi and Its Effect on Preventing Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice via Antioxidant Activity

“…Its production can be regulated by IL-1, interferon, and TNF-α [50]. IL-12 is an inflammatory cytokine that can induce cytotoxic activity of CTL and NK cells and promote their secretion of IFN-gamma, TNF-α, GM-CSF, and other cytokines [51]. TNF-α is the earliest and most important inflammatory mediator during the process of inflammation.…”

Opposing Roles of DCs and iNKT Cells in the Induction of Foxp3 Expression by MLN CD25+CD4+ T Cells during IFNγ-Driven Colitis

“…Moreover, mice in which the ARE region of the IFNγ gene is deleted exhibit increased IFNγ mRNA stability and develop typical autoimmune symptoms characteristic of Th1-type hyperimmune responses [ 4 ]. Polymorphisms in the IFNγ gene are associated with disease severity in major forms of human inflammatory bowel diseases (IBDs), such as Crohn’s disease and ulcerative colitis [ 5 ].…”