Bittencourt Paulo Lisboa, Palácios Selma Aliotti, Farias Alberto Queiroz, Abrantes-Lemos Clarice Pires, Cançado Eduardo Luiz Rachid, Carrilho Flair José, Laudanna Antonio Atílio, Kalil Jorge, Goldberg Anna C
Portuguese Hospital of Salvador, Rua Tamoios 314, Rio Vermelho, Salvador-Bahia, Brazil CEP: 41940-040.
J Gastroenterol Hepatol. 2003 Sep;18(9):1061-6. doi: 10.1046/j.1440-1746.2003.03091.x.
Predisposition to primary biliary cirrhosis (PBC) has been classically linked to HLA-DRB1 locus. However, the presence of the HLA-DRB108 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-DRB108 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.
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.
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.
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.
原发性胆汁性肝硬化（PBC）的易感性传统上与HLA - DRB1基因座相关。然而，据报道，来自北欧和日本的PBC患者中，HLA - DRB108抗原的阳性率不到三分之一。最近，肿瘤坏死因子α（TNFA）基因启动子-308位点的多态性以及细胞毒性T淋巴细胞抗原4（CTLA - 4）基因第1外显子49位点的多态性与白种人PBC易感性相关。此外，HLA - DRB108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来自不同遗传背景的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。
采用基于聚合酶链反应的技术，对PBC患者和健康对照者进行HLA - DRB1、DQB1、TNFA和CTLA - 4等位基因的检测。
PBC患者和健康对照者中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与HLA抗原、TNFA和CTLA - 4等位基因无相关性。
巴西PBC的易感性与HLA - DR和DQ抗原以及CTLA - 4基因型无关。未显示TNFA等位基因影响疾病进展。
