696 FUT2 Genotype Is Not Associated With Disease Phenotype or Outcomes in Patients With Crohn's Disease

Abstract

INTRODUCTION: The fucosyltransferase 2 gene (FUT2) is responsible for the regulation of mucosal blood type antigens which can act as receptors for bacterial adhesion and regulate intestinal flora. A homozygous non-sense mutation in this gene leads to the absence of these antigens, termed FUT2 nonsecretor status, and is associated with the development of Crohn's disease (CD). The mechanism of this association is likely via changes in homeostatic symbiosis thus promoting development of inflammation. However, the impact of FUT2 genotype on CD phenotype and outcomes is not known. METHODS: Patients were prospectively enrolled into a single center translational IBD registry. All patients with CD who had available DNA extracted from peripheral blood for genotyping were included. Genotyping was performed using the rs601338-AA SNP, which represents the nonsense mutation (428GA) shown to be causing nonsecretor status. Baseline demographics, disease phenotype, CD-related surgery, and hospitalization were also assessed retrospectively and statistically compared based on FUT2 genotype. RESULTS: 635 patients with CD were studied including 178 wild-type (WT), 314 heterozygous (HET) and 143 homozygous (O) patients. The mean duration of follow up was 8 years 2 months. There were no significant differences detected between genotypes when comparing sex, race, smoking, body-mass index, and age of onset. Presence of extra-intestinal manifestations including arthritis, uveitis, erythema nodosum, pyoderma gangrenosum, and PSC, as well as disease location and behavior were also found to be similar when compared between O vs WT, O vs HET, and O vs HET + WT groups. The mean number of biologics used between groups was 1.50 (O), 1.39 (HET) and 1.42 (WT) (P = 0.55), with no difference in first or total duration of biologic therapy between groups. 60.8% of O patients used immunomodulators compared to 54.8% of HET and 59.6% of WT patients. In addition, there were no differences in the number of patients who required >1 CD-related hospitalization (O = 30.1%, HET = 34.1%, WT = 30.3%) or surgery (O = 32.2%, HET = 39.5%, WT = 32%) with the entire cohort having a mean of 1.46 for hospitalization and 1.43 for surgery, respectively. CONCLUSION: In this single center analysis of 635 patients with Crohn's Disease, FUT2 genotype was not associated with disease phenotype, disease severity, or clinical outcomes. This may be due to the fact that lack of fucosylation is a more of a causative factor but does not contribute to disease progression in CD.