Association of FUT2 and ABO with Crohn's disease in Koreans.

Abstract

Fucosyltransferase 2 (FUT2) at 19q13 is a well-established susceptibility locus for Crohn's disease (CD) in Caucasians. FUT2 encodes α-1,2-fucosyltransferase that regulates the secretion of the α-1-2-N-acetylgalactosaminyltransferase and α-1-3-galactosyltransferase (ABO) antigens in both the gastrointestinal mucosa and secretory glands. Given that CD is thought to arise from dysregulated mucosal immune responses to the gut flora and both the ABO blood group and the FUT2 secretor status affect the composition of the gut microbiota, the goal of this study was to evaluate the associations of variants of FUT2 and ABO with CD in Koreans. Three single-nucleotide polymorphisms from the FUT2 and ABO genes were genotyped in 1735 patients with CD and 8074 healthy controls. The FUT2 non-secretor allele showed genome-wide significant association with CD in Koreans (rs1047781, odds ratio [OR]=1.30, Pcombined =3.52×10-12 ). The ABO locus showed genome-wide significant association with CD in Asians (Pmeta =2.35×10-8 ). A moderate association was observed with the A and B groups (OR=1.40, P = 2.26×10-6 ; and OR=1.32, P = 1.92×10-4 , respectively) compared with the O group. Following stratification on the basis of FUT2 genotype, carriers of the secretor O blood group were significantly protective against CD than were those of the secretor non-O blood group (OR=0.63, 95% confidence interval=0.54-0.73, P = 2.86×10-9 ). These are the first results indicating that the O blood group and FUT2 secretor status are protective factors against CD in Asians.