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

Wei Yu, John P. Hegarty, Arthur Berg, Ashley A. Kelly, Yunhua Wang, Lisa Poritz, Andre Franke, Stefan Schreiber, Walter Koltun, Zhenwu Lin

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalDisease Markers
Volume32
Issue number2
DOIs
StatePublished - 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Clinical Biochemistry
  • Biochemistry, medical

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