PTPN2 is associated with Crohn's disease and its expression is regulated by NKX2-3

Dis Markers. 2012;32(2):83-91. doi: 10.3233/DMA-2011-0867.

Abstract

PTPN2 is a risk gene for Crohn's disease (CD). We investigated whether PTPN2 genetic variants (rs2542151 and rs2542152) were associated with CD in a familial IBD registry. Both rs2542151 and rs2542152 are associated with CD, but not ulcerative colitis (UC). mRNA expression levels of PTPN2 were significantly increased in intestinal tissues (p=0.0493), and nearly significantly increased in B cells (p=0.0889) from CD patients, but not significantly altered in UC. cDNA microarray results found that PTPN2 was down-regulated by NKX2-3 knockdown in human cells. We confirmed this observation by RT-PCR analyses in NKX2-3 knockdown in B cells from IBD patients and human intestinal microvascular endothelial cells (HIMEC). In addition, we found that mRNA expression of another IBD-associated gene, NKX2-3, was increased in intestinal tissues and B cells from CD patients, but not significantly increased in UC patients. A positive correlation was observed between mRNA expression of PTPN2 and NKX2-3 in B cells and in intestinal tissues from both CD and UC patients. These results suggest that PTPN2 may have an important role in CD pathogenesis and may represent a potential diagnostic and therapeutic target for IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / metabolism
  • Case-Control Studies
  • Cells, Cultured
  • Colitis, Ulcerative / genetics
  • Colitis, Ulcerative / pathology
  • Crohn Disease / genetics*
  • Crohn Disease / pathology
  • Down-Regulation
  • Gene Expression Regulation*
  • Genetic Association Studies
  • Genotype
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Homeodomain Proteins / physiology*
  • Humans
  • Polymorphism, Single Nucleotide
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transcription, Genetic

Substances

  • Homeodomain Proteins
  • NKX2.3 protein, human
  • RNA, Messenger
  • Transcription Factors
  • PTPN2 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2