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Disease Markers
Volume 32 (2012), Issue 2, Pages 83-91

PTPN2 is Associated with Crohn’s Disease and Its Expression Is Regulated by NKX2-3

Wei Yu,1 John P. Hegarty,1 Arthur Berg,2 Ashley A. Kelly,1 Yunhua Wang,1 Lisa S. Poritz,1,3 Andre Franke,4 Stefan Schreiber,4 Walter A. Koltun,1 and Zhenwu Lin1

1Department of Surgery, Pennsylvania State University, Hershey, PA, USA
2Department of Public Health Sciences, Center for Statistical Genetics, Pennsylvania State University, Hershey, PA, USA
3Department of Cellular & Molecular Physiology, Pennsylvania State University, Hershey, PA, USA
4Institute for Clinical Molecular Biology, Department of General Internal Medicine, Christian-Albrechts University, Kiel, Germany

Received 23 February 2012; Accepted 23 February 2012

Copyright © 2012 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.