Analysis of major histocompatibility complex and CTLA-4 alleles in Brazilian patients with primary biliary cirrhosis
Analysis of major histocompatibility complex and CTLA-4 alleles in Brazilian patients with primary biliary cirrhosis
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DOI：
10.1046/j.1440-1746.2003.03091.x
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发表时间：
2003-09-01
影响因子：
4.1
通讯作者：
Goldberg, AC
中科院分区：
文献类型：
--
作者：
Bittencourt, PL;Palácios, SA;Goldberg, AC
背景和目的：原发性胆汁性肝硬化 (PBC) 的易感性通常与 HLA-DRB1 基因座相关。然而，据报道，北欧和日本不到三分之一的 PBC 患者存在 HLA-DRB1*08 抗原。最近，肿瘤坏死因子 α (TNFA) 基因启动子 -308 位和细胞毒性 T 淋巴细胞抗原 4 (CTLA-4) 基因外显子 1 49 位的多态性与白种人 PBC 易感性相关。此外，HLA-DRB1*08 和 TNFA*1 等位基因的存在也与终末期肝病的进展有关。本研究的目的是调查不同遗传背景的 PBC 患者中 HLA-DR 和 DQ 抗原以及 TNFA 和 CTLA-4 等位基因的频率，并评估 TNFA 等位基因和 HLA-DR 抗原在疾病进展中的作用。 方法：采用基于聚合酶链反应的方法测定 PBC 患者和健康对照者的 HLA-DRB1、DQB1、TNFA 和 CTLA-4 等位基因。结果：PBC 患者和健康对照中 HLA-DR 和 DQ 抗原的频率相似。因此，在 PBC 患者中未观察到 TNFA 和 CTLA-4 等位基因之间的关联。 PBC患者入院时的组织学分期也显示与HLA抗原以及TNFA和CTLA-4等位基因没有相关性。结论：巴西人对PBC的易感性与HLA-DR和DQ抗原以及CTLA-4基因型无关。 TNFA 等位基因并未显示出影响疾病进展。 (C) 2003 年布莱克威尔出版亚洲有限公司。
Background and Aims: Predisposition to primary biliary cirrhosis (PBC) has been classically linked to HLA-DRB1 locus. However, the presence of the HLA-DRB1*08 antigen has been reported in less than one-third of PBC patients from Northern Europe and Japan. Recently, polymorphisms in the tumor necrosis factor alpha (TNFA) gene promoter at position -308 and in exon 1 of the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene at position 49 have been associated with susceptibility to PBC in Caucasians. In addition, the presence of HLA-DRB1*08 and the TNFA*1 allele was also linked to progression to end-stage liver disease. The aims of the present study were to investigate the frequencies of HLA-DR and DQ antigens and TNFA and CTLA-4 alleles in PBC patients from a different genetic background, as well as to assess the role of TNFA alleles and HLA-DR antigens in disease progression.Methods: Determination of HLA-DRB1, DQB1, TNFA and CTLA-4 alleles was performed in patients with PBC and healthy controls using polymerase chain reaction-based techniques.Results: Frequencies of HLA-DR and DQ antigens were similar in PBC patients and healthy controls. Accordingly, no association between TNFA and CTLA-4 alleles was observed in PBC patients. The histological stage at admission of patients with PBC also showed no correlation with HLA antigens and TNFA and CTLA-4 alleles.Conclusions: Susceptibility to PBC in Brazil is not associated with HLA-DR and DQ antigens and CTLA-4 genotypes. TNFA alleles were not shown to influence disease progression. (C) 2003 Blackwell Publishing Asia Pty Ltd.