Dataset Information

ATG16L1 T300A polymorphism is associated with Crohn's disease in a Northwest Greek cohort, but ECM1 T130M and G290S polymorphisms are not associated with ulcerative colitis.

ABSTRACT: Background:Crohn's disease (CD) and ulcerative colitis (UC) are well-described disease entities with unknown etiopathogenesis. Environmental, genetic, gut microbiota, and host immune response correlations have been implicated. The role of susceptibility gene polymorphisms, such as ATG16L1 T300A and ECM1 T130M and G290S, is well-described, although controversial findings have been reported. Methods:Two hundred five patients with inflammatory bowel disease (108 CD and 97 UC), and 223 healthy blood donors (control group) from the Northwest Greece region were genotyped for rs2241880 (T300A), rs3737240 (T130M) and rs13294 (G290S) single nucleotide polymorphisms. Genotyping was performed using the real-time polymerase chain reaction method. Results:The frequency of G allele was significantly higher in CD patients compared to the control group (P=0.029; odds ratio [OR] 1.45, 95% confidence interval [CI] 1.04-2.03). Carriers of two G alleles (T300A), compared to those carrying only one, were 1.3 times more susceptible to CD (P=0.022; OR 2.45, 95%CI 1.14-5.27). In CD patients, the presence of the T300A polymorphism indicates a possible protective effect against developing a penetrating (B3) phenotype, while in UC patients, presence of the T300A polymorphism, indicates a possible protective effect against developing joint-involving extraintestinal manifestations. Conclusion:Our study found a significant association of the T300A polymorphism with CD susceptibility, suggesting that CD occurrence in our population has a strong genetic background, with the T300A G allele having an additive effect.

SUBMITTER: Tsianos VE

PROVIDER: S-EPMC6928472 | biostudies-literature | 2020 Jan-Feb

REPOSITORIES: biostudies-literature

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<i>ATG16L1</i> T300A polymorphism is associated with Crohn's disease in a Northwest Greek cohort, but <i>ECM1</i> T130M and G290S polymorphisms are not associated with ulcerative colitis.

Tsianos Vasileios E VE Kostoulas Charilaos C Gazouli Maria M Frillingos Stathis S Georgiou Ioannis I Christodoulou Dimitrios K DK Katsanos Konstantinos H KH Tsianos Epameinondas V EV

Annals of gastroenterology 20191121 1

<h4>Background</h4>Crohn's disease (CD) and ulcerative colitis (UC) are well-described disease entities with unknown etiopathogenesis. Environmental, genetic, gut microbiota, and host immune response correlations have been implicated. The role of susceptibility gene polymorphisms, such as ATG16L1 T300A and ECM1 T130M and G290S, is well-described, although controversial findings have been reported.<h4>Methods</h4>Two hundred five patients with inflammatory bowel disease (108 CD and 97 UC), and 22 ...[more]

PMID: 31892796

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Project description:Autophagy-related 16-like 1 (ATG16L1) deficiency leads to impaired cellular autophagy and bacterial degradation as well as an altered cytokine production. The single-nucleotide polymorphism rs2241880 (T300A) is associated with an increased risk for Crohn's disease (CD). ATG16L1 polymorphisms could therefore have an impact on the risk of infectious complications and disease course in CD. We examined the impact of the T300A genotype on the antibacterial response toward a panel of pathogenic bacteria in vitro, as well as clinical infectious complications in vivo and the disease course in a Danish cohort of patients with CD.A total of 236 CD patients were genotyped for ATG16L1(T300A); their clinical records were reviewed, and microbial, radiological, and surgical data were scrutinized. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and CD patients carrying the different ATG16L1 genotypes, and the production of tumor necrosis factor (TNF)-? and interleukin (IL)-1? was measured by enzyme-linked immunosorbent assay after stimulation with a panel of pathogenic bacteria of clinical relevance for the gastrointestinal tract, e.g., enteroinvasive Escherichia coli (EIEC), Listeria monocytogenes, Salmonella typhimurium, Staphylococcus aureus, or Mycobacterium avium paratuberculosis.Fifty-seven healthy controls (15, 29, 13) and 236 patients with CD (50, 108, 78) were genotyped for the T300A ATG16L1 polymorphism (AA homozygous, GG homozygous risk variant, AG heterozygous variant, respectively). The median duration of disease was 128 months (range, 30-175). The cumulative follow-up of this cohort was 2,366 patient-years. ATG16L1 gene variations interfered with the production of IL-1?, which was significantly increased in PBMCs from GG patients in response to all tested bacteria, whereas the TNF-? production was decreased in PBMCs from GG patients stimulated with EIEC, L. monocytogenes, and S. typhimurium, but unaffected by the other bacteria tested. Moreover, the GG variant showed a nonsignificant increase in the risk of bowel resections (P=0.07) and postsurgical infections (P=0.08), whereas the risk of non-disease-related infections was unaffected by genotype in the observation period. In addition, patients with AA and AG variants had a higher frequency of complicated fistulizing disease (P=0.03) with an overall more aggravated disease course with an increased number of surgical procedures for fistulous disease from a median 6.5 operations (2.0 in GG patients; P=0.002). This risk was independent on disease phenotype (penetrating vs. non-penetrating) and immunomodulating medication.The T300A variant in patients with CD strongly increases the risk for complicated fistulizing disease, and significantly affects antibacterial responses in vitro, but the latter effect seems to have a minor role for the infectious risk in CD.

Dataset Information

ATG16L1 T300A polymorphism is associated with Crohn's disease in a Northwest Greek cohort, but ECM1 T130M and G290S polymorphisms are not associated with ulcerative colitis.

Publications

<i>ATG16L1</i> T300A polymorphism is associated with Crohn's disease in a Northwest Greek cohort, but <i>ECM1</i> T130M and G290S polymorphisms are not associated with ulcerative colitis.

Similar Datasets

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