Association of Fucosyltransferase 2 Gene Polymorphisms with Inflammatory Bowel Disease in Patients from Southeast China

Abstract

Aims. Fucosyltransferase 2 (FUT2) gene potentially affects the constituent of intestinal microbiota, which play a crucial role in the pathogenesis of inflammatory bowel disease (IBD). This study investigated the association of FUT2 gene polymorphisms with IBD in southeast China. Methods. We collected 671 IBD patients and 502 healthy controls. FUT2 gene polymorphisms (C357T, A385T, and G428A) were determined by SNaPshot. Frequencies of the FUT2 genotypes, alleles, and haplotype between groups were compared by χ2 test. Results. The allele and genotype frequencies of FUT2 did not differ between ulcerative colitis patients and controls (all P > 0.05). However, mutant allele and genotype of FUT2 (A385T) were significantly increased in Crohn's disease (CD) patients (P = 0.024, OR = 1.271, and 95% CI = 1.031–1.565; P < 0.001, OR = 1.927, and 95% CI = 1.353–2.747, resp.). The same conclusion was drawn from FUT2 (G428A) (P = 0.023, OR = 3.324, and 95% CI = 1.108–9.968; P = 0.044, OR = 1.116–10.137, and 95% CI = 1.116–10.137, resp.). The haplotype TT formed with “C357T and A385T” was more prevalent in CD patients than in controls (P = 0.020, OR = 1.277, and 95% CI = 1.036–1.573). Besides, frequencies of mutant allele and genotype of FUT2 (A385T) were significantly lower in patients with ileocolonic CD than in those with colonic CD (P = 0.001 and 0.002, resp.) and ileal CD (P = 0.007 and 0.004, resp.). Conclusions. FUT2 gene polymorphisms and haplotypes were associated with the susceptibility to CD but not UC.

FUT2 genotype and secretory status are not associated with fecal microbial composition and inferred function in healthy subjects

“…The minor allele (A) confers a nonsecretor phenotype and is associated with Crohn's disease (CD) susceptibility with odds ratio of 1.11 (1.071-1.143 95% CI, p < 10 ¡15 ). [13][14][15] Host-microbe interactions can involve FUT2 through modification of components of the mucus layer, [16][17][18][19] and thus FUT2 is an ideal candidate to test for association with the gut microbiota variability. Indeed several studies have already investigated the role of FUT2 in the composition of the microbiota but large biological (mucosal versus stool sample or bile duct) and technical differences (DNA extraction and profiling method of the microbiota) exist between studies resulting in potentially different results.…”

Exogenous l ‐fucose protects the intestinal mucosal barrier depending on upregulation of FUT2‐mediated fucosylation of intestinal epithelial cells

“…Fucosyltransferase 2 (FUT2) is one of the detected gene variants in IBD patients, and it is associated with predisposition to IBD in patients of various races. [10][11][12][13] Aheman et al reported that FUT2 gene variants are associated with UC in Han and Uyghur patients in western China. 12 Parmar et al discovered a significant FUT2 mutation in Finish patients with UC and CD.…”

Microbe-set enrichment analysis facilitates functional interpretation of microbiome profiling data

“…Specifically, CCL11 , an eosinophil-specific chemokine, is significantly elevated in serum of Crohn’s disease patients versus normal controls 27 and has been shown to be a central mediator for eosinophil recruitment in colon 28 . The genetic polymorphisms of Fucosyltransferase 2 ( FUT2 ) have also been associated with Crohn’s diseases in multiple independent genome-wide association studies from distinctive populations 29 , 30 . The role of Autophagy Related 16 Like 1 ( ATG16L1 ) in Crohn’s diseases is even more well-characterized by a large body of literature (See 26 for a comprehensive review).…”