Underhill J A, Donaldson P T, Doherty D G, Manabe K, Williams R
Institute of Liver Studies, King's College Hospital, London, England.
Hepatology. 1995 Apr;21(4):959-62.
In recent years there has been an increasing interest in the link between susceptibility to autoimmune liver disease and genes of the HLA system, although the role of the DPB1 locus in British patients has only been investigated in autoimmune hepatitis. The aim of the current study was to determine the distribution of DPB1 alleles in a large series of British patients with the two other autoimmune liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis, and compare the allele frequencies obtained with those of a geographically matched control group. Polymerase chain reaction sequence-specific oligonucleotide probing was used to assign 18 DPB1 alleles in 82 patients with primary biliary cirrhosis (PBC), 71 patients with primary sclerosing cholangitis (PSC), and 103 controls. The frequencies of the DPB1 alleles were not significantly different comparing patients and controls. However, two important observations were made. Firstly, in primary sclerosing cholangitis, the previously reported association with the haplotype A1-B8-DR3-DQ2 does not extend to the DPB1 locus, suggesting that the genetic determinants of susceptibility for this disease lie closer to the DRB loci. Secondly, in primary biliary cirrhosis there is evidence that the reported association with DR8-DQB10402 includes the DPB10301 allele. The weak HLA association reported here is in contrast with recent data from Japan, where susceptibility is strongly linked to a particular amino acid residue encoded by the DPB1*0501 allele. These data clearly demonstrate that the alleles of the DPB1 locus are not associated with susceptibility to or protection from either primary biliary cirrhosis or primary sclerosing cholangitis in British patients.
近年来，人们对自身免疫性肝病易感性与HLA系统基因之间的联系越来越感兴趣，尽管DPB1基因座在英国患者中的作用仅在自身免疫性肝炎中进行过研究。本研究的目的是确定一大系列患有另外两种自身免疫性肝病（原发性胆汁性肝硬化和原发性硬化性胆管炎）的英国患者中DPB1等位基因的分布，并将获得的等位基因频率与地理匹配的对照组进行比较。采用聚合酶链反应序列特异性寡核苷酸探针技术，对82例原发性胆汁性肝硬化（PBC）患者、71例原发性硬化性胆管炎（PSC）患者和103例对照者的18种DPB1等位基因进行分型。患者和对照者的DPB1等位基因频率无显著差异。然而，有两个重要发现。首先，在原发性硬化性胆管炎中，先前报道的与单倍型A1-B8-DR3-DQ2的关联并不延伸至DPB1基因座，这表明该疾病易感性的遗传决定因素更靠近DRB基因座。其次，在原发性胆汁性肝硬化中，有证据表明所报道的与DR8-DQB10402的关联包括DPB10301等位基因。此处报道的HLA弱关联与日本最近的数据形成对比，在日本，易感性与DPB1*0501等位基因编码的特定氨基酸残基密切相关。这些数据清楚地表明，DPB1基因座的等位基因与英国患者原发性胆汁性肝硬化或原发性硬化性胆管炎的易感性或抵抗力无关。
