Differential Effect of Genetic Burden on Disease Phenotypes in Crohn's Disease and Ulcerative Colitis in a Canadian Cohort.

Autor:	Pang JXQ; Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada., Kheirkhahrahimabadi H; Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada., Bindra S; Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada., Bindra G; Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada., Panaccione R; Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada., Eksteen B; Current Address: Aspen Woods Clinic, Calgary, Alberta, Canada., Kaplan GG; Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada., Nasser Y; Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada., Beck PL; Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada., Jijon HB; Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada.
Jazyk:	angličtina
Zdroj:	Journal of the Canadian Association of Gastroenterology [J Can Assoc Gastroenterol] 2020 Feb 03; Vol. 4 (2), pp. 65-72. Date of Electronic Publication: 2020 Feb 03 (Print Publication: 2021).
DOI:	10.1093/jcag/gwaa002
Abstrakt:	Background and Aims: Crohn's disease (CD) and ulcerative colitis (UC) demonstrate considerable phenotypic heterogeneity and course. Accurate predictors of disease behaviour are lacking. The contribution of genetics and specific polymorphisms is widely appreciated; however, their cumulative effect(s) upon disease behaviour remains poorly understood. Here, we investigate the relationship between genetic burden and disease phenotype in a Canadian inflammatory bowel disease (IBD) Cohort. Methods: We retrospectively examined a cohort of CD and UC patients recruited from a single tertiary referral center genotyped using a Goldengate Illumina platform. A genetic risk score (GRS) incorporating strength of association (log odds ratio) and allele dose for 151 IBD-risk loci was calculated and evaluated for phenotypic associations. Results: Among CD patients, higher GRS was associated with earlier onset of disease (regression coefficient -2.19, 95% confidence interval [CI] -3.77 to -0.61, P = 0.007), ileal disease (odds ratio [OR] 1.45), stricturing/penetrating disease (OR 1.72), perianal disease (OR 1.57) and bowel resection (OR 1.66). Higher GRS was associated with use of anti-tumor necrosis factor (TNF) ( P < 0.05) but not immunomodulators. Interestingly, we could not demonstrate an association between higher GRS and family history of IBD (OR 1.27, P = 0.07). Onset of disease remained statistically significant for never smokers ( P = 0.03) but not ever smokers ( P = 0.13). For UC, having a higher GRS did not predict the age of diagnosis nor was it predictive of UC disease extent ( P = 0.18), the need for surgery ( P = 0.74), nor medication use (immunomodulators P = 0.53, anti-TNF P = 0.49). We could not demonstrate an association between increased GRS and having a family history of IBD in the UC group. Conclusions: Increasing genetic burden is associated with early age of diagnosis in CD and may be useful in predicting disease behaviour in CD but not UC. (© The Author(s) 2020. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)
Databáze:	MEDLINE
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