P440 Identification of DMBT1 single nucleotide polymorphisms and their haplotypes as novel susceptibility variants for Crohn's disease and ulcerative colitis

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.

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Single Nucleotide Polymorphisms in Selected Genes in Inflammatory Bowel Disease

BioMed Research International ◽

10.1155/2018/6914346 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 4

Author(s):

Ewa Dudzińska ◽

Magdalena Gryzinska ◽

Janusz Kocki

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bowel Disease ◽

Disease Patient ◽

Nucleotide Polymorphisms ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Inflammatory Bowel

Introduction. Inflammatory bowel disease (IBD) is a complicated, multifunctional disorder characterized by chronic, recurring inflammation of the digestive tract. The two main types of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). The aim of the study was to determine single nucleotide polymorphism in fragments of the genes CARD15/NOD2 and DLG5 in patients from the Lublin Voivodeship. Patients and Methods. The study was carried out in Lublin (Poland) in 2016. 27 individuals participated in the research. The research group comprised 9 patients with a diagnosis of Crohn’s disease and 9 with ulcerative colitis, aged 20 to 48, and 9 healthy volunteers. Results. No SNPs were confirmed for the CARD15/NOD2 gene fragment, but a substitution (T>C) was found in the DLG5 gene in a Crohn’s disease patient. Conclusion. Absence of extraintestinal symptoms in patients with Crohn’s disease may be associated with the absence of CARD15/NOD2 SNPs. The study suggests that SNPs (T>C substitution) affect the function of the DLG5 protein and thus play a role in the development of IBD, in particular Crohn’s disease. The analysis presented is a pilot study due to the small number of samples.

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