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    Predicting complicated Crohn’s disease and surgery: phenotypes, genetics, serology and psychological characteristics of a population based cohort

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    Date
    2012-08
    Author
    Ryan, John David
    Silverberg, Mark
    Xu, Wei
    Graff, Lesley A.
    Targownik, Laura
    Walker, John R.
    Carr, Rachel
    Clara, Ian
    Miller, Norine
    Rogala, Linda
    Bernstein, Charles N.
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    Abstract
    BACKGROUND: Predictors of complicated Crohn's disease (CD), defined as stricturing or penetrating behaviour, and surgery have largely been derived from referral centre populations. AIM: To investigate whether serological markers, susceptibility genes or psychological characteristics are associated with complicated CD or surgery in a population-based cohort. METHODS: One hundred and eighty-two members of the Manitoba IBD Cohort with CD phenotyped using the Montreal classification underwent genetic and serological analysis at enrolment and after 5 years. One hundred and twenty-seven had paired sera at baseline and 5 years later and their data were used to predict outcomes at a median of 9.3 years. Serological analysis consisted of a seven antibody panel, and DNA was tested for CD-associated NOD2 variants (rs2066845,rs2076756,rs2066847), ATG16L1 (rs3828309, rs2241880) and IL23R (rs11465804). Psychological characteristics were assessed using semi-structured interviews and validated survey measures. RESULTS: Sixty-five per cent had complicated CD and 42% underwent surgery. Multivariate analysis indicated that only ASCA IgG-positive serology was predictive of stricturing/penetrating behaviour (OR = 3.01; 95% CI: 1.28-7.09; P = 0.01) and ileal CD (OR = 2.2; 95% CI: 1.07-4.54, P = 0.03). Complicated CD behaviour was strongly associated with surgery (OR = 5.6; 95% CI: 2.43-12.91; P < 0.0001), whereas in multivariate analysis, only ASCA IgG was associated (OR = 2.66; 95% CI, 1.40-5.06, P = 0.003). ASCA titre results were similar at baseline and follow-up. Psychological characteristics were not significantly associated with disease behaviour, serological profile or genotype. CONCLUSIONS: ASCA IgG at baseline was significantly associated with stricturing/penetrating disease at 9-10 years from diagnosis. Stricturing/penetrating disease was significantly associated with surgery. In a model including serology, the genotypes assessed did not significantly associate with complicated disease or surgery.
    URI
    http://hdl.handle.net/1993/30418
    DOI
    10.1111/apt.12368
    Collections
    • Rady Faculty of Health Sciences Scholarly Works [1296]
    • University of Manitoba Scholarship [1952]

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