title: PTPN2 is associated with Crohn's disease and its expression is regulated by NKX2-3.
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.
authors.affiliation: Department of Surgery, Pennsylvania State University, Hershey, PA, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: John P
authors.initials: JP
authors.lastname: Hegarty
authors.forename: Arthur
authors.initials: A
authors.lastname: Berg
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Kelly
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Poritz
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Walter A
authors.initials: WA
authors.lastname: Koltun
authors.forename: Zhenwu
authors.initials: Z
authors.lastname: Lin
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000235:genetics / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D018398:Homeodomain Proteins; C534957:NKX2-3 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2