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

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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
Publication statusPublished - Jan 1 2012

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All Science Journal Classification (ASJC) codes

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

Cite this

Yu, W., Hegarty, J. P., Berg, A., Kelly, A. A., Wang, Y., Poritz, L., ... Lin, Z. (2012). PTPN2 is associated with Crohn's disease and its expression is regulated by NKX2-3. Disease Markers, 32(2), 83-91. https://doi.org/10.3233/DMA-2011-0867