The Clinical Relevance of the IBD-Associated Variation within the Risk Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 2 in Patients of the Swiss IBD Cohort

Digestion. 2016;93(3):182-92. doi: 10.1159/000444479. Epub 2016 Feb 27.

Abstract

Background/aims: The single nucleotide polymorphism (SNP) rs1893217 within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) results in a dysfunctional PTPN2 protein is associated with Crohn's disease (CD) and exists in perfect linkage disequilibrium with the CD- and ulcerative colitis (UC)-associated PTPN2 SNP rs2542151. We investigated associations of PTPN2 SNP rs1893217 and clinical characteristics of inflammatory bowel disease (IBD) patients.

Methods: One thousand seventy three patients with CD and 734 patients with UC from the Swiss IBD Cohort Study (SIBDCS) were included. Epidemiologic, disease and treatment characteristics were analysed for an association with the presence of one of the rs1893217 genotypes 'homozygous wild-type' (TT), 'heterozygous' (CT) and 'homozygous variant' (CC).

Results: About 2.88% of IBD patients were identified with CC, 26.8% with CT and 70.4% with TT genotype. The CC-genotype was associated with the existence of gallstones in CD and pancolitis in UC patients. The presence of the C-allele (i.e. either CC or CT genotype) was associated with the onset of uveitis, but protected from aphthous oral ulcers in CD patients. UC patients carrying a C-allele were diagnosed at an older age but required intestinal surgery more often. The presence of the C-allele was associated with a successful treatment with anti-TNF antibodies in both CD and UC patients.

Conclusion: IBD patients carrying the C-allele of PTPN2 SNP rs1893217 are at greater risk for developing a severe disease course but are more likely to respond to treatment with anti-TNF antibodies. These findings demonstrate a clinical relevance of this PTPN2 risk variant in IBD patients.

MeSH terms

  • Adalimumab / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Certolizumab Pegol / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Gastrointestinal Agents / therapeutic use
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Infant
  • Inflammatory Bowel Diseases / epidemiology
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / therapy*
  • Infliximab / therapeutic use
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / genetics*
  • Risk Factors
  • Switzerland / epidemiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Young Adult

Substances

  • Gastrointestinal Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • PTPN2 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2
  • Adalimumab
  • Certolizumab Pegol