A population-based case-control study of CARD15 and other risk factors in Crohn's disease and ulcerative colitis.

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.