Jiang Yi, Xia Bing, Jiang Li, Lv Min, Guo Qiusha, Chen Min, Li Jin, Xia Harry Hua-Xiang, Wong Benjamin Chun-Yu
Department of Internal Medicine & Geriatrics, Research Center of Digestive Diseases, Zhongnan Hospital, Key Laboratory of Allergy and Immune-related Diseases, Wuhan University School of Medicine, Wuhan, China.
Inflamm Bowel Dis. 2006 May;12(5):369-73. doi: 10.1097/01.MIB.0000217339.61183.dd.
Ulcerative colitis (UC) is characterized by chronic intestinal inflammation as a result of an exaggerated T cell response. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4), expressed mainly in activated T cells, inhibits T cell activation and proliferation by combining B7 through competing CD28 and maintains immune homeostasis. Polymorphisms of the CTLA-4 gene are known to be associated with several autoimmune diseases. The aim of this study was to investigate the association between the CTLA-4 gene microsatellite polymorphism and UC in Chinese patients. Unrelated 100 Chinese patients with UC and 140 healthy controls were studied. The (AT) repeats in the 3' untranslated region of exon 4 of the CTLA-4 gene were amplified by allele-specific polymerase chain reaction (PCR). The amplified products were electrophoresed on a 12% polyacrylamide gel, followed by silver staining. Twenty alleles were found in Chinese patients and healthy controls. The 122-bp allele was increased in UC compared with healthy controls (9.5% vs 0.7%, P = 0.0001/Pc = 0.002, OR = 14.591, 95%CI 3.357-63.420). The frequency of the longer alleles (>or=118 bp) of UC was higher than that in healthy controls (26% vs 4%, P = 0.0001/Pc = 0.0002, OR = 7.644, 95%CI 3.950-14.792), but was not associated with location and severity of the disease. Furthermore, the longer alleles were not associated with haplotypes of C-318T/A+49G of the CTLA-4 gene in Chinese patients with UC. The longer alleles of the CTLA-4 gene microsatellite polymorphism were strongly associated with UC in Chinese patients.
溃疡性结肠炎（UC）的特征是由于T细胞反应过度而导致的慢性肠道炎症。细胞毒性T淋巴细胞相关抗原4（CTLA-4）主要在活化的T细胞中表达，通过与B7结合竞争CD28来抑制T细胞活化和增殖，并维持免疫稳态。已知CTLA-4基因的多态性与多种自身免疫性疾病相关。本研究的目的是调查中国UC患者中CTLA-4基因微卫星多态性与UC的关联。研究了100例无血缘关系的中国UC患者和140例健康对照。通过等位基因特异性聚合酶链反应（PCR）扩增CTLA-4基因第4外显子3'非翻译区的（AT）重复序列。扩增产物在12%聚丙烯酰胺凝胶上进行电泳，然后进行银染。在中国患者和健康对照中发现了20个等位基因。与健康对照相比，UC患者中122-bp等位基因增加（9.5%对0.7%，P = 0.0001/Pc = 0.002，OR = 14.591，95%CI 3.357-63.420）。UC患者中较长等位基因（≥118 bp）的频率高于健康对照（26%对4%，P = 0.0001/Pc = 0.0002，OR = 7.644，95%CI 3.950-14.792），但与疾病的部位和严重程度无关。此外，在中国UC患者中，较长等位基因与CTLA-4基因的C-318T/A+49G单倍型无关。CTLA-4基因微卫星多态性的较长等位基因与中国UC患者的UC密切相关。
