Fucosyltransferase 2 A Genetic Risk Factor for Pr

Authors: Luca Maroni Stan F J van de Graaf Simon D Hohenester Ronald P J Oude Elferink Ulrich Beuers

Publish Date: 2014/05/15

Volume: 48, Issue: 2-3, Pages: 182-191

PDF Link

Abstract

Fucosyltransferase 2 FUT2 mediates the inclusion of fucose in sugar moieties of glycoproteins and glycolipids ABO blood group antigens and hostmicrobe interactions are influenced by FUT2 activity About 20  of the population has a “nonsecretor” status caused by inactivating variants of FUT2 on both alleles The nonsense mutation G428A and the missense mutation A385T are responsible for the vast majority of the nonsecretor status in Caucasians Africans and Asians respectively Nonsecretor individuals do not secrete fucosepositive antigens and lack fucosylation in epithelia They also appear to be protected against a number of infectious diseases such as Norovirus and Rotavirus infections In recent years genomewide 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 These associations are intriguing given the important roles of fucosylated glycans in hostmicrobe interactions and membrane stability Nonsecretors have a reduced fecal content of Bifidobacteria The intestinal bacterial composition of CD patients resembles the one of nonsecretors with an increase in Firmicutes and decreases in Proteobacteria and Actinobacteria Nonsecretor individuals lack fucosylated glycans at the surface of biliary epithelium and display a different bacterial composition of bile compared to secretors Notably an intact biliary epithelial glycocalix is relevant for a stable ‘biliary HCO3 − umbrella’ to protect against toxic effects of hydrophobic bile salt monomers Here the biology of FUT2 will be discussed as well as hypotheses to explain the role of FUT2 in the pathophysiology of PSC and Crohn’s disease

Keywords: