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A population-based case-control study of CARD15 and other risk factors in Crohn's disease and ulcerative colitis
Steven R Brant1, Ming-Hsi Wang, Patricia Rawsthorne
1Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Insights
Crohn's disease (CD) and ulcerative colitis (UC) are influenced by CARD15/NOD2 mutations, family history, smoking, and Jewish ethnicity. These factors collectively contribute to the epidemiological understanding and genetic counseling for inflammatory bowel disease.
Area of Science:
- Gastroenterology
- Genetics
- Epidemiology
Background:
- Established risk factors for Crohn's disease (CD) and ulcerative colitis (UC) include family history, tobacco use, Jewish ethnicity, urban residency, and CARD15/NOD2 mutations.
- Previous studies often evaluated these factors individually in hospital-based settings.
Purpose of the Study:
- To assess the combined contributions of known risk factors for CD and UC.
- To evaluate these factors within a nonreferral, population-based cohort using an epidemiologic database.
Main Methods:
- Utilized a population-based Inflammatory Bowel Disease (IBD) Registry from Manitoba Health for CD (N=232) and UC (N=121) ascertainment.
- Recruited healthy controls (N=336) matched by age, sex, and postal code.
- Determined ethnicity, tobacco use, family history, residency, and CARD15/NOD2 genotype status.
Main Results:
- For CD, independent risk factors included CARD15/NOD2 genotype (heterozygote OR 3.7, homozygote/compound-heterozygote OR 40.0), Jewish ethnicity (OR 18.5), family history (OR 6.2), and smoking (current OR 3.0, ex-smoker OR 1.7).
- Population attributable risk was 26.7% for CARD15 and 46.8% for current tobacco use in CD.
- UC was associated with Jewish ethnicity (OR 37.1), family history (OR 2.6), ex-smoker status (OR 1.9), and CARD15/NOD2 status (heterozygote OR 1.9, homozygote/compound-heterozygote OR 6.4) in adjusted analyses.
Conclusions:
- CARD15/NOD2 mutations, family history, smoking, and Jewish ethnicity are confirmed as independent risk factors for Crohn's disease.
- This population-based study provides initial data for epidemiological characterization and genetic counseling in IBD.
Objectives:
Multiple established Crohn's disease (CD) and ulcerative colitis (UC) risk factors including family history, tobacco use, Jewish ethnicity, urban residency, and CARD15/NOD2 mutations have been evaluated singly and in hospital-based observational studies. The goal of this study was to assess the relative contributions of all these risk factors jointly in a nonreferral, population-based cohort derived from a population epidemiologic database.
Methods:
CD (N = 232) and UC (N = 121) subjects were ascertained from our population-based IBD Registry derived from Manitoba Health, the single provincial insurer. Healthy controls (HC) (N = 336) were recruited via a 10:1 mailing matched for age, sex, and postal code. Ethnicity, tobacco use, family history, residency, and CARD15/NOD2 genotype status were determined.
Results:
In both univariate analyses and analyses adjusted for all risk factors, CD was influenced independently by CARD15/NOD2 heterozygote and homozygote/compound-heterozygote status (adjusted odds ratios [OR] 3.7 and 40.0, respectively), Jewish ethnicity (OR 18.5), CD family history (OR 6.2), and smoking (OR 3.0 current and 1.7 ex-smoker, respectively). Penetrance for homozygote/compound-heterozygotes was 4.9%, heterozygotes 0.54%, and wild types 0.184%. Population attributable risk for CARD15 was 26.7% and current tobacco use was 46.8%. A tobacco-CARD15 interaction was not observed. UC was influenced by Jewish ethnicity (OR 37.1), and by family history (OR 2.6), ex-smoker status (OR 1.9), and CARD15/NOD2 heterozygote or homozygote/compound-heterozygote status (OR 1.9 and 6.4, respectively) in adjusted analyses only.
Conclusions:
CARD15/NOD2, family history, smoking, and Jewish ethnicity are independent risk factors for CD. Examination of these risk factors together in a single population-based cohort has provided initial data for population epidemiological characterization and genetic counseling uses.
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