TNFSF15 is an independent predictor for the development of Crohn's disease-related complications in Koreans

J Crohns Colitis. 2014 Oct;8(10):1315-26. doi: 10.1016/j.crohns.2014.04.002. Epub 2014 May 14.

Abstract

Background: Crohn's disease (CD) is a chronic idiopathic inflammatory bowel disease involving the whole gastrointestinal tract. TNFSF15 has been proved as a susceptibility gene for CD, but there are few reports about the association between TNFSF15 single nucleotide polymorphisms (SNPs) and the clinical course of CD.

Aim: To investigate the association between TNFSF15 genotypes and the clinical course of CD in Koreans.

Methods: A total of 906 CD patients having TNFSF15 genotype data and clinical information were recruited from CD registry database of a tertiary referral center. The association between five TNFSF15 SNPs (rs4574921, rs3810936, rs6478108, rs6478109, and rs7848647) and various clinical parameters including stricture, non-perianal penetrating complications, bowel resection, and reoperation was investigated.

Results: Among the five SNPs, rs6478108 CC genotype was associated with the development of stricture and non-perianal penetrating complications during follow-up (HR for stricture=1.706, 95% confidence interval 1.178-2.471, P=0.005; HR for non-perianal penetrating complications=1.667, 95% confidence interval 1.127-2.466, P=0.010), and rs4574921 CC genotype was associated with the development of perianal fistula (HR=2.386, 95% confidence interval 1.204-4.727, P=0.013) by multivariate analysis. However, there was no significant association of cumulative operation and reoperation rate with 5 SNPs of TNFSF15.

Conclusion: In Korean patients with CD, non-risk allele homozygotes of TNFSF15 SNPs rs6478108 and rs4574921 are independent genetic predictive factors for the development of strictures/non-perianal penetrating complications and perianal fistula, respectively.

Keywords: Complication; Crohn's disease; Single nucleotide polymorphism; TNFSF15.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Constriction, Pathologic / genetics
  • Constriction, Pathologic / surgery
  • Crohn Disease / complications*
  • Crohn Disease / genetics*
  • Crohn Disease / surgery
  • Female
  • Genotype
  • Humans
  • Intestines / pathology*
  • Intestines / surgery
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Rectal Fistula / etiology
  • Rectal Fistula / genetics*
  • Rectal Fistula / surgery
  • Reoperation
  • Republic of Korea
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / genetics*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Young Adult

Substances

  • TNFSF15 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 15
  • Tumor Necrosis Factor-alpha