FUT2 non-secretor status is not associated with disease phenotype or outcomes in patients with Crohn’s disease

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Abstract
Purpose: 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 nonsense mutation in this gene leads to the absence of these antigens, termed FUT2 non-secretor 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: Subjects 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 non-secretor status. Baseline demographics, disease phenotype, CD-related surgeries, and hospitalizations were also assessed retrospectively and statistically compared based on FUT2 genotype. Results: 635 patients with CD were included in the analysis, including 178 FUT2 wild-type (WT), 314 heterozygous (HET) and 143 homozygous (O) patients. The mean duration of follow-up was 8 years and 2 months. There were no statistically significant differences detected between genotypes when comparing sex, race, smoking status, body-mass index, and age of onset. Presence of extra-intestinal manifestations including arthritis, uveitis, erythema nodosum, pyoderma gangrenosum and primary sclerosing cholangitis, as well as disease location and behavior were also found to be similar when compared between O and WT, O and HET, and O and HET plus WT populations. The mean number of biologics used between groups was 1.50 (O), 1.39 (HET)and 1.42 (WT) (P = .55), with no difference in 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 between groups in the number of patients who required more than one CD-related hospitalization (O = 30.1%, HET = 34.1%, WT = 30.3%) or surgery (O = 32.2%, HET = 39.5%, WT = 32%). Conclusion: In this single-center analysis of 635 patients with CD, the FUT2 genotype was not associated with disease phenotype, disease severity, or clinical outcomes. These data suggest that while lack of fucosylation is associated with developing CD, it does not play a major role in driving disease progression.

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