Affiliations: Department of Surgery, Pennsylvania State University,
Hershey, PA, USA | Department of Public Health Sciences, Center for
Statistical Genetics, Pennsylvania State University, Hershey, PA, USA | Department of Cellular & Molecular Physiology,
Pennsylvania State University, Hershey, PA, USA | Institute for Clinical Molecular Biology, Department
of General Internal Medicine, Christian-Albrechts University, Kiel,
Germany
Note: [] Corresponding author: Walter A. Koltun, MD and Zhenwu Lin, PhD.
Division of Colon & Rectal Surgery. Mail code H137. The Milton S.
Hershey Medical Center, Penn State College of Medicine, 500 University Drive,
P.O. Box 850, Hershey, PA 17033, USA. Tel.: +1 717 531 5164; Fax: +1 717 531
0646; E-mail: wkoltun@hmc.psu.edu
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.
