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目的炎症性肠病(IBD)的发病机制与T细胞免疫应答过度有关。细胞毒T淋巴细胞相关抗原-4(CTLA-4)主要在已激活的T细胞上表达,通过与CD28竞争与B7结合,抑制T细胞激活,维持免疫系统内环境稳定。CTLA-4基因多态性与一些自身免疫性疾病相关,但未见与炎症性肠病的研究。本文研究CTLA-4基因多态性与炎症性肠病的相关性,旨在阐明炎症性肠病的遗传易感性。方法对68例无血缘关系的湖北汉族炎症性肠病患者(54例溃疡性结肠炎,14例克罗恩病)以及140例正常对照者,采用序列特异性引物PCR方法检测CTLA-4外显子4的3’非转录区包含AT重复序列的特异性等位基因。扩增产物用12%非变性聚丙烯酰胺凝胶电泳,硝酸银染色,部分样品经测序以确定片段长度。结果共发现CTLA-4基因有18种等位基因,其中122bp等位基因与正常对照组比较,在溃疡性结肠炎患者中显著增高(7.4%vs0.3%,P=0.0002/Pc=Sig,OR=22.320,95%CI:2.755～180.80)。结论CTLA-4基因微卫星多态性与溃疡性结肠炎显著相关。
The purpose of the pathogenesis of inflammatory bowel disease (IBD) and T-cell immune response over. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is mainly expressed on activated T cells and competes with CD28 for binding to B7 to suppress T cell activation and maintain the stable internal environment of the immune system. CTLA-4 gene polymorphisms are associated with some autoimmune diseases, but no studies have been done with inflammatory bowel disease. This article studies CTLA-4 gene polymorphism and inflammatory bowel disease, aims to clarify the genetic susceptibility to inflammatory bowel disease. Methods Sixty-eight unrelated Han patients with inflammatory bowel disease (54 ulcerative colitis, 14 Crohn’s disease) and 140 normal controls were enrolled in this study. Sequence-specific PCR was used to detect the expression of CTLA-4 The 3 ’untranslated region of daughter 4 contains the specific allele of the AT repeat. The amplified product was electrophoresed on a 12% non-denaturing polyacrylamide gel, stained with silver nitrate, and some of the samples were sequenced to determine the fragment length. RESULTS: A total of 18 alleles were found in the CTLA-4 gene. The 122 bp allele was significantly higher in patients with ulcerative colitis than in the normal controls (7.4% vs 0.3%, P = 0.0002 / Pc = Sig, OR = 22.320, 95% CI: 2.755-180.80). Conclusion The microsatellite polymorphism of CTLA-4 gene is significantly associated with ulcerative colitis.