ABO histo-blood group might modulate predisposition to Crohn's disease and affect disease behavior

Background and aims: ABO encodes a glycosyltranferase which determines the major human histo-blood group. The FUT2 fucosyltransferase allows expression of ABO antigens on the gastrointestinal mucosa and in bodily secretions (secretor phenotype). A nonsense allele in FUT2 represents a susceptibility variant for Crohn's disease, and both the secretor and ABO blood group status affect the composition of the gut microbiota. Thus, we evaluated if variants in ABO might represent good candidates as Crohn's disease susceptibility loci. Methods: We recruited two case-control cohorts, from Italy (n. = 1301) and Belgium (n. = 2331). Subjects were genotyped for one SNP in FUT2 and two variants in ABO. Results: No effect on Crohn's disease risk was detected for ABO variants, whereas an association was observed between the FUT2 polymorphism and Crohn's disease susceptibility in the Belgian sample, but not in the Italian cohort. The effect of histo-blood groups was evaluated using group O as the reference. Most non-O groups had odds ratios (ORs) higher than 1 in both cohorts, and combined analysis of the two samples indicated a predisposing effect for the A and B groups (OR. = 1.17, 95% CI: 1.02-1.32 and OR. = 1.33, 95% CI: 1.09-1.58, respectively). In Crohn's disease patients, the non-O blood group and the non-secretor status were associated with higher risk of developing a stricturing or penetrating disease. Conclusions: ABO histo-blood group might confer susceptibility to Crohn's disease and modulate disease severity.