蛋白酪氨酸磷酸酶非受体型22基因-1123G/C多态性与溃疡性结肠炎的相关性

Association of Protein Tyrosine Phosphatase Nonreceptor Type 22 Gene-1123G/C Polymorphism with Ulcerative Colitis

目的:研究蛋白酪氨酸磷酸酶非受体型22基因(PTPN22)启动子区-1123G/C和外显子10区+788G/A多态性与湖北汉族溃疡性结肠炎(UC)的相关性,检测UC患者肠黏膜PTPN22mRNA表达。方法:收集105例UC患者和200名健康对照者,采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测PTPN22基因-1123G/C和+788G/A位点多态性。实时定量PCR方法检测肠黏膜PTPN22mRNA表达。结果:UC患者PTPN22基因-1123G/C位点C等位基因和"CC+CG"基因型频率显著高于正常对照组(42.4%比32.5%,P=0.016,OR=1.53,95%CI:1.08-2.16;67.6%比51.5%,P=0.009,OR=1.93,95%CI:1.18-3.16),且与广泛性结肠炎相关(P=0.035)。活动期UC患者肠黏膜PTPN22mRNA的水平显著高于缓解期UC患者(P=0.005)。UC患者PTPN22基因-1123G/C多态性与肠黏膜PTPN22mRNA的水平无关。UC组+788G/A基因型频率与对照组比,差异无统计学意义。结论:PTPN22基因启动子区-1123G/C位点C等位基因与湖北汉族UC相关,活动性UC患者肠黏膜PTPN22mRNA水平增高,提示PTPN22基因在UC遗传免疫发病机制中可能起重要作用。

Objective： To investigate the -1123G/C in the promoter and ＋788G/A in exon 10 polymor- phisms of protein tyrosine phosphatase nonreceptor type 22 （PTPN22） gene on disease suscepti- bility and phenotype of ulcerative colitis （UC）, and explore the expression of PTPN22 mRNA in colonic biopsies of UC. Methods： A total of 105 UC patients and 200 healthy controls were geno- typed for -1123G/C and q-788G/A of the PTPN22 gene polymorphisms using a method of poly-merase chain reaction based restriction fragment length polymorphism. PTPN22 mRNA expres- sion in colonic biopsies of UC patients and controls was determined by quantitative PCR. Results. The frequencies of C allele and ＂CC ＋ CG＂ genotype were higher in UC patients than in healthy controls （42.4%vs 32.5%, P = 0. 016, OR=I. 53, 95% CI. 1.08-2.16% 67.6% vs 51.5%, P =0. 009, OR=I. 93, 95% CI. 1.18-3.16）, and associated with extensive colitis （P=0. 035）. In UC patients, PTPN22 mRNA expression levels were elevated in active disease compared with in- active disease （P=0. 005）. There was no association of PTPN22 mRNA expression levels with -1123G/C polymorphism in UC patients. The distribution of ＋788G/A allele and genotype fre- quencies did not differ between UC patients and the healthy controls. Conclusion. Our study showed the potential association between PTPN22 -1123G/C polymorphism and UC in central China. PTPN22 mRNA expression levels were highly expressed in colonic biopsies of active UC. It suggests that PTPN22 may plays an important role in pathogenesis of UC.