Department of Surgery, Pennsylvania State University, Hershey, PA, USA.
Dis Markers. 2012;32(2):83-91. doi: 10.3233/DMA-2011-0867.
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.
PTPN2 是克罗恩病（CD）的风险基因。我们在一个家族性 IBD 登记处调查了 PTPN2 遗传变异（rs2542151 和 rs2542152）是否与 CD 相关。rs2542151 和 rs2542152 均与 CD 相关，但与溃疡性结肠炎（UC）无关。来自 CD 患者的肠道组织（p=0.0493）和 B 细胞（p=0.0889）中 PTPN2 的 mRNA 表达水平显著增加，但在 UC 中未发生显著改变。cDNA 微阵列结果发现，NKX2-3 敲低可下调人细胞中的 PTPN2。我们通过在 IBD 患者的 B 细胞和人肠微血管内皮细胞（HIMEC）中进行 NKX2-3 敲低的 RT-PCR 分析证实了这一观察结果。此外，我们发现另一个与 IBD 相关的基因 NKX2-3 的 mRNA 表达在 CD 患者的肠道组织和 B 细胞中增加，但在 UC 患者中未显著增加。在 CD 和 UC 患者的 B 细胞和肠道组织中，PTPN2 和 NKX2-3 的 mRNA 表达之间存在正相关。这些结果表明 PTPN2 可能在 CD 的发病机制中具有重要作用，并且可能代表 IBD 的潜在诊断和治疗靶点。
