Polymorphisms of PTPN11 coding SHP-2 as biomarkers for ulcerative colitis susceptibility in the Japanese population

J Clin Immunol. 2009 May;29(3):303-10. doi: 10.1007/s10875-008-9272-6. Epub 2009 Jan 22.

Abstract

Objective: To identify genetic determinants of inflammatory bowel disease (IBD), we examined an association between polymorphisms of both the programmed cell death 1 gene (PDCD1) and the src homology 2 domain-containing tyrosine phosphatase 2 gene (PTPN11) and susceptibility to IBD.

Methods: Study subjects comprised 114 patients with ulcerative colitis (UC), 83 patients with Crohn's disease, and 200 healthy control subjects. Five single nucleotide polymorphisms (SNPs) in PDCD1 and PTPN11 were detected by polymerase chain reaction restriction fragment length polymorphism. Subsequently, haplotypes composed of the two SNPs in PTPN11 were constructed.

Results: The frequencies of the Hap 1 haplotype and its homozygous Hap 1/Hap 1 diplotype of PTPN11 were significantly increased in UC patients compared to control subjects (P = 0.011 and P = 0.030, respectively). While no association was found for PDCD1 for UC or CD and none for PTPN11 for CD.

Conclusion: PTPN11 is a genetic determinant for the pathogenesis of UC, and haplotyping of PTPN11 may be useful as a genetic biomarker to identify high-risk individuals susceptible to UC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / genetics*
  • Apoptosis Regulatory Proteins / genetics*
  • Biomarkers / metabolism
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / physiopathology
  • Crohn Disease / diagnosis
  • Crohn Disease / genetics*
  • Crohn Disease / physiopathology
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Programmed Cell Death 1 Receptor
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics*

Substances

  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • Biomarkers
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11