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

Authors:
Wei Yu, John P Hegarty, Arthur Berg, Ashley A Kelly, Yunhua Wang, Lisa S Poritz, Andre Franke, Stefan Schreiber, Walter A Koltun, Zhenwu Lin
Year of publication:
2012
Volume:
32
Issue:
2
Issn:
0278-0240
Journal title abbreviated:
DIS MARKERS
Journal title long:
Disease markers : a Wiley medical publication
Impact factor:
2.137
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.