HLA class II alleles, genotypes, haplotypes, and amino acids in primary biliary cirrhosis: A large-scale study
HLA class II alleles, genotypes, haplotypes, and amino acids in primary biliary cirrhosis: A large-scale study
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DOI：
10.1002/hep.21316
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发表时间：
2006-09-01
期刊：
影响因子：
13.5
通讯作者：
Bassendine, Margaret F.
中科院分区：
文献类型：
--
作者：
Donaldson, Peter T.;Baragiotta, Anna;Bassendine, Margaret F.
双胞胎和家庭研究表明，原发性胆汁性肝硬化（PBC）有一个显着的遗传成分。然而，无法复制报道的关联一直是一个反复出现的问题，唯一一致报道的遗传关联是PBC和HLA-DRB 1 *0801之间的关联。然而，最近连这一点也受到了质疑，一些新奇的联想也被报道出来。我们重新调查了492例特征明确的PBC患者的HLA II类DRB 1、DQA 1和DQB 1等位基因和单倍型，其中412例来自英国，另外80例来自北方意大利。与人群特异性健康对照相比，两组患者中的HILA-DRB 1 *0801均存在明确且显著的相关性（英国患者中为12% vs 4%，P = 0.00087，OR = 3.05;意大利患者中为18% vs 6%，P = 0.021，OR = 3.15）。在意大利患者中，DRB 1 *11也有显著的保护性相关性。（28%对47%，P = 0.0071，OR = 0.42），但在英国患者中并非如此（8%对8%），并在两个系列中与DRB 1 *13保护性相关（英国患者为14%对20%，P = 0.042，OR = 0.65;意大利患者为10%对31%，P = 0.00092，OR = 0.25）。总之，HILA和PBC之间存在着复杂的关系，并且某些遗传关联可能是人群特异性的。
Twin and family studies suggest there is a significant genetic component to primary biliary cirrhosis (PBC). However, the inability to replicate reported associations has been a recurring problem, with the only consistently reported genetic association that between PBC and HLA-DRB1*0801. However, recently even this has been questioned, and a number of novel associations have also been reported. We reinvestigated HLA class II DRB1, DQA1, and DQB1 alleles and haplotypes in a total of 492 well-characterized PBC patients, 412 from the United Kingdom and an additional 80 patients from northern Italy. There was a clear and significant association with HILA-DRB1*0801 in both groups of patients compared to population-specific healthy controls (12% versus 4% in the UK patients, P = .00087, OR = 3.05; and 18% versus 6% in the Italian patients, P = .021, OR = 3.15). There were also significant protective associations with DRB1*11 in the Italian patients (28% versus 47%, P = .0071, OR = 0.42), but not in the UK patients (8% versus 8%) and a protective association with DRB1*13 in both series (14% versus 20%, P = .042, OR = 0.65 in the UK patients; and 10% versus 31%, P = .00092, OR = 0.25 in the Italian patients). In conclusion, a complex relationship exists between HILA and PBC, and some genetic associations may be population specific.