Association of Ulcerative Colitis with FUT2 and FUT3 Polymorphisms in Patients from Southeast China

PLoS One. 2016 Jan 14;11(1):e0146557. doi: 10.1371/journal.pone.0146557. eCollection 2016.

Abstract

Objectives: Dysbiosis of intestinal microbiota has been implicated in ulcerative colitis (UC). Fucosyltransferase (FUT) 2 and FUT3 determine expression of histo-blood group antigens in the gut and may affect the intestinal microbiota. We investigated the association between FUT2 and FUT3 polymorphisms and UC in Chinese patients.

Methods: We genotyped FUT2 (rs281377, rs1047781 and rs601338) and FUT3 (rs28362459, rs3745635 and rs3894326) in 485 UC patients and 580 healthy controls using SNaPshot. We also evaluated expression of Lewis a and b antigens in the sigmoid colon of 7 UC patients and 7 patients with benign colonic polyps.

Results: The frequencies of mutant allele (A) and genotype (GA+AA) in FUT3 (rs3745635) were higher in UC patients than controls (P = 0.016, 95%CI: 1.339-1.699; P = 0.038, 95%CI: 1.330-1.742, respectively). Stratified analyses revealed that the frequencies of mutant allele (G) and genotype (TG+GG) of FUT3 (rs28362459) were significantly lower in patients with extensive colitis than those with distal colitis (P<0.001, 95%CI: 0.503-0.742; P = 0.001, 95%CI: 0.567-0.786, respectively). Similar conclusions were drawn for the mutant allele (A) and genotype (GA+AA) of FUT3 (rs3745635) in patients with extensive colitis compared to those with distal colitis (P = 0.006, 95%CI: 0.553-0.845; P = 0.011, 95%CI: 0.621-0.900, respectively). Although expression of Lewis b antigen in the sigmoid colon did not differ between UC patients and controls, Lewis a antigen expression was higher in the cryptic epithelium of both inflammatory and non-inflammatory sigmoid colon of UC patients than controls (P = 0.028).

Conclusions: Our findings indicated that polymorphisms in FUT3 and its intestinal expression might be associated with UC pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • China
  • Colitis, Ulcerative / genetics*
  • Female
  • Fucosyltransferases / genetics*
  • Fucosyltransferases / metabolism
  • Humans
  • Intestinal Mucosa / metabolism
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • Fucosyltransferases
  • 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase
  • galactoside 2-alpha-L-fucosyltransferase

Grant support

The study project was supported by grants from Natural Science Foundation of Zhejiang Province (Grant number: LY14H030012, http://www.zjnsf.gov.cn/; recipient: YJ) and Zhejiang Provincial Health Bureau (Grant number: 2014KYB157 and 2012KYA132, http://www.zjwst.gov.cn/; recipient: YJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.