A population-based case-control study of CARD15 and other risk factors in Crohn's disease and ulcerative colitis.
OBJECTIVE
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.
Brant
Steven R
SR
Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Wang
Ming-Hsi
MH
Rawsthorne
Patricia
P
Sargent
Michael
M
Datta
Lisa Wu
LW
Nouvet
Franklin
F
Shugart
Yin Yao
YY
Bernstein
Charles N
CN
D000293:Adolescent; D000328:Adult; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics*; D003424:Crohn Disease / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007585:Jews; D008297:Male; D008350:Manitoba / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011159:Population Surveillance; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014505:Urban Population
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D004247:DNA