Several studies have been conducted to investigate the association of fucosyltransferase 2 gene (rs601338) variant with UC and CD, but the results were inconsistent.
In recent years, genome-wide association studies (GWAS) identified inactivating variants at the FUT2 locus to be associated with primary sclerosing cholangitis (PSC), Crohn's disease (CD), and biochemical markers of biliary damage.
Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease.
Although a causing viral infectious agent remains untraceable in Crohn's disease, most recent genome-wide association studies have linked the FUT2W143X mutation (resulting in asymptomatic norovirus infection) with the pathogenesis of Crohn's ileitis and with vitamin B12 deficiency (i.e., a known risk factor for Crohn's disease with ileal involvement).
Therefore, the colonic microbiota of non-secretors is altered at both the compositional and functional levels, affecting the host mucosal state and potentially explaining the association of FUT2 genotype and CD susceptibility.
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.
Individuals lacking a functional copy of FUT2 are known as "nonsecretors" and display an array of differences in susceptibility to infection and disease, including Crohn disease.
We demonstrated replication in an independent cohort of 1174 CD cases and 357 controls between the four primary FUT2 single nucleotide polymorphisms (SNPs) and CD (rs602662, combined P-value 4.90x10(-8)) and also association with FUT2W143X (P=2.6x10(-5)).