Genetic Markers and Radiologic Disease Activity in Crohnʼs Disease: Results From a Cohort at a Tertiary Care IBD Referral Center

Abstract

Introduction: Several studies have examined association between serologic/immunologic biomarkers and outcome parameters among Crohn's disease (CD) patients. Impact of serologic/immunologic biomarkers on CD outcomes is difficult to study due to their variability over time. Contrary to this, genotypes are time independent. We studied association between select IBD specific genetic markers and radiologic disease activity (RDA) in CD patients seen at a U.S. tertiary care IBD referral center. Methods: Adult CD patients >19 years followed for at least one year between 2014 and 2016 at our IBD center and tested for presence of ATG16L1, ECM1, NKX2-3 genotypes (associated with IBD) and absence of STAT3 genotype (associated with IBD) at initial observation were included. Radiologic data including CT/MR enterography and MRI/CT Abdomen and pelvis were reviewed. We performed univariate analyses to examine incidence rates of moderate to severely active radiologic disease among CD patients based on presence or absence of above genotypes. We built Generalized Poisson Regression Models (GPR) for Rate Data to estimate adjusted (for age, sex, race, duration of disease, steroid use, biologic use, methotrexate use, azathioprine use) incidence rate ratios (IRR) of radiologic active disease based on dichotomous assessment at each clinic visit among CD patients with presence vs. absence of selected IBD specific genotypes. Results: Of the 76 CD patients with available genetic markers, 54 were followed in clinic for at least one year. Of these, 45 (83%) had positive genotype ATG16L1, 28 (52%) had positive ECM1, 42 (78%) had NKX2-3 and 25 (46%) lacked STAT3 genotype respectively (Table 1). Among CD patients, incidence rate of radiologic active disease was 81.48 per 100 person-years for genotype ATG16L1, 90.63 per 100 person-years for genotype ECM1, 75.51 per 100 person-years for genotype NKX2-3, 86.21 per 100 person-years for absence of genotype STAT3. GPR Model for Rate Data when adjusted showed that CD patients with genotypes ATG16L1 (IRR 1.34, 95%CI 0.54 - 3.27) and ECM1 (IRR 1.12, 95%CI 0.54 - 2.33) had slightly higher rate of radiologic active disease during the observation period (Table 2). These associations did not reach statistical significance.Table: Table. Characteristic description of Crohn's disease patients by Genetic MarkersTable: Table. Rates and Rate Ratios of Crohn's Disease Related Radiologic Disease Activity (RDA)Conclusion: Presence of ATG16L1 and ECM1 genotypes may play a role in predicting radiologic active disease in CD. However, further study of these associations in larger samples is needed to better elucidate their overall impact on CD outcomes.