细胞毒性T淋巴细胞相关抗原4基因多态性与炎症性肠病的相关性

Association between the cytotoxic T lymphocyte antigen-4 gene microsatellite polymorphism and inflammatory bowel diseases in the Chinese

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CD2 8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 ,但未见其与IBD的研究。本研究旨在了解IBD的遗传易感性。方法 对 68例无血缘关系的湖北汉族IBD患者 (54例溃疡性结肠炎 ,14例克罗恩病 )以及 14 0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 ,与正常对照组比较 ,12 2bp等位基因在溃疡性结肠炎患者中显著增高 (7 4%vs 0 3 % ,P =0 0 0 0 2 /Pc =Sig ,OR =2 2 3 2 ,95%CI :2 76～ 180 80 )。结论 CTLA

ObjectiveInflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation as a result of an exaggerated T-cell response. Cytotoxic T lymphocyte antigen-4 (CTLA-4) expressed mainly on activated T cells,inhibits T cell activation by combining B 7 through competing CD 28 and maintains immune system homeostasis. Polymorphisms in the CTLA-4 gene are known to be associated with several autoimmune diseases, but no studies related to IBD. The aim of the study is to investigate an association between CTLA-4 gene microsatellite polymorphisms and IBD. MethodsUnrelated 68 Chinese Han patients with IBD (54 ulcerative colitis and 14 Crohn′s disease) and 140 healthy controls were studied. The (AT)n repeat sequence in the 3′ untranslated region of exon 4 were amplified by allele-specific PCR. The amplified products were electrophorosised by 12% polyacrylamid gel and followed by silver staining. ResultsEighteen alleles of CTLA-4 microsatellite were found in Chinese patients and healthy individuals. Long allele, 122bp was apparently increased in patients with ulcerative colitis compared with healthy controls (7.4% vs 0.3%, P=0.0002/Pc=Sig, OR=22.32, 95%CI: 2.76～180.80). ConclusionCTLA-4 gene microsatellite polymorphism was strongly associated with ulcerative colitis in Chinese Han patients in Hubei province.