Associations of FUT2 and FUT3 gene polymorphisms with Crohn's disease in Chinese patients

Abstract

Our study strongly implicates the polymorphic locus of FUT2 (rs1047781) in CD susceptibility in Chinese population. Mutations of FUT3 (rs28362459) and (rs3745635) might influence the lesion locations in CD patients.

Distribution of Lewis and Secretor polymorphisms and corresponding CA19‐9 antigen expression in a Chinese population

“…In a large cohort of 316 Chinese participants, we performed accurate genotyping and a combined analysis of nine SNPs reported previously in the fucosyltransferase genes . False‐negative reactions are often produced in Lewis blood typing due to weak hemagglutination reactions, which in the main is accounted for by adsorption of glycolipids and by erythrocyte levels .…”

“…Cooperation of the two fucosyltransferases ultimately regulates the expression of the histo‐blood group antigens, including CA19‐9 (sLe a ), in body fluids and on the surface of epithelial cells. A single nucleotide polymorphism (SNP) of FUT3 and FUT2 is prevalent in multiple populations and dramatically determines the fucosyltransferase activities . Distribution of the FUT3 / FUT2 genotypes exhibits ethnic heterogeneity and is strongly associated with a wide range of human diseases .…”

“…However, Lewis‐positive individuals (the Le / Le and Le / le genotypes) are divided into three Lewis‐secretor phenotypes according to distinct Secretor genotypes as follows: (a) Le (a−b+) secretors with the Se / Se or Se / se genotype; (b) Le (a+b−) non‐secretors with the se / se genotype; and (c) Le (a+b+) partial secretors having homozygosity for the weak Secretor allele . Nucleotide substitutions inactivating the FUT2 / 3 genes have been found within various populations, and the phenotypes have been determined by the ethnic group‐specific genotypes . Both genotypes of Lewis and Secretor are crucial for an individual's phenotype formation, and the serum CA19‐9 value will directly reflect the differences among individuals.…”

Host genetic variation in mucosal immunity pathways influences the upper airway microbiome

“…Interestingly, the non-secretor phenotype, characterized by a null variant in another FUT gene, FUT2 , and the resulting absence of ABH antigens in the mucosa in homozygotes for the null allele, influences the composition and diversity of the microbiome in the human intestinal tract (Wacklin et al 2011; Rausch et al 2011). Moreover, variants in both FUT2 and FUT3 have been shown in GWAS to increase susceptibility to diseases associated with both mucosal surface pathobiology and microbiome composition, such as cystic fibrosis (Taylor-Cousar et al 2009), Crohn’s disease (Hu et al 2014) and ulcerative colitis (Hu et al 2016). Our study extends a role for fucosyltransferases to the nasal mucosal surface, and further implicates host genetic influences on bacterial diversity at this site.…”

Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet's disease susceptibility

“…We found significant associations of rs601338 with disease in Turks ( P =6.51×10 −9 ) and in Iranians ( P =1.65x10 −5 ), and also significant association of rs1047781 in Japanese ( P =6.50×10 −4 , Supplementary Table 15). These non-secretor genotypes are also associated with Crohn’s disease risk 26,27 and with the gut microbiome composition 28,29 . The non-secretor phenotype has also been associated with increased predisposition to or resistance to different infectious agents 30–32 .…”