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Genetic polymorphisms associated with smoking behaviour predict the risk of surgery in patients with Crohn's disease


Lang, B M; Biedermann, L; van Haaften, W T; de Vallière, C; Schuurmans, M; Begré, S; Zeitz, J; Scharl, M; Turina, M; Greuter, T; Schreiner, P; Heinrich, H; Kuntzen, T; Vavricka, S R; Rogler, G; Beerenwinkel, N; Misselwitz, B; Swiss IBD Cohort Study Group (2018). Genetic polymorphisms associated with smoking behaviour predict the risk of surgery in patients with Crohn's disease. Alimentary Pharmacology & Therapeutics, 47(1):55-66.

Abstract

BACKGROUND Smoking is a strong environmental factor leading to adverse outcomes in Crohn's disease, but a more benign course in ulcerative colitis. Several single nucleotide polymorphisms (SNPs) are associated with smoking quantity and behaviour. AIM To assess whether smoking-associated SNPs interact with smoking to influence the clinical course of inflammatory bowel diseases. METHODS Genetic and prospectively obtained clinical data from 1434 Swiss inflammatory bowel disease cohort patients (821 Crohn's disease and 613 ulcerative colitis) were analysed. Six SNPs associated with smoking quantity and behaviour (rs588765, rs1051730, rs1329650, rs4105144, rs6474412 and rs3733829) were combined to form a risk score (range: 0-12) by adding the number of risk alleles. We calculated multivariate models for smoking, risk of surgery, fistula, Crohn's disease location and ulcerative colitis disease extent. RESULTS In Crohn's disease patients who smoke, the number of surgeries was associated with the genetic risk score. This translates to a predicted 3.5-fold (95% confidence interval: 2.4- to 5.7-fold, P<.0001) higher number of surgical procedures in smokers with 12 risk alleles than individuals with the lowest risk. Patients with a risk score >7 had a significantly shorter time to first intestinal surgery. The genetic risk score did not predict surgery in ulcerative colitis or occurrence of fistulae in Crohn's disease. SNP rs6265 was associated with ileal disease in Crohn's disease (P<.05) and proctitis in ulcerative colitis (P<.05). CONCLUSIONS SNPs associated with smoking quantity is associated with an increased risk for surgery in Crohn's disease patients who smoke. Our data provide an example of genetics interacting with the environment to influence the disease course of inflammatory bowel disease.

Abstract

BACKGROUND Smoking is a strong environmental factor leading to adverse outcomes in Crohn's disease, but a more benign course in ulcerative colitis. Several single nucleotide polymorphisms (SNPs) are associated with smoking quantity and behaviour. AIM To assess whether smoking-associated SNPs interact with smoking to influence the clinical course of inflammatory bowel diseases. METHODS Genetic and prospectively obtained clinical data from 1434 Swiss inflammatory bowel disease cohort patients (821 Crohn's disease and 613 ulcerative colitis) were analysed. Six SNPs associated with smoking quantity and behaviour (rs588765, rs1051730, rs1329650, rs4105144, rs6474412 and rs3733829) were combined to form a risk score (range: 0-12) by adding the number of risk alleles. We calculated multivariate models for smoking, risk of surgery, fistula, Crohn's disease location and ulcerative colitis disease extent. RESULTS In Crohn's disease patients who smoke, the number of surgeries was associated with the genetic risk score. This translates to a predicted 3.5-fold (95% confidence interval: 2.4- to 5.7-fold, P<.0001) higher number of surgical procedures in smokers with 12 risk alleles than individuals with the lowest risk. Patients with a risk score >7 had a significantly shorter time to first intestinal surgery. The genetic risk score did not predict surgery in ulcerative colitis or occurrence of fistulae in Crohn's disease. SNP rs6265 was associated with ileal disease in Crohn's disease (P<.05) and proctitis in ulcerative colitis (P<.05). CONCLUSIONS SNPs associated with smoking quantity is associated with an increased risk for surgery in Crohn's disease patients who smoke. Our data provide an example of genetics interacting with the environment to influence the disease course of inflammatory bowel disease.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Pneumology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Pharmacology (medical)
Language:English
Date:January 2018
Deposited On:19 Jan 2018 07:57
Last Modified:19 Aug 2018 12:52
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0269-2813
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/apt.14378
PubMed ID:29052254

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