HLA class II genotype influences the type of liver injury in drug-induced idiosyncratic liver disease
HLA class II genotype influences the type of liver injury in drug-induced idiosyncratic liver disease
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DOI：
10.1002/hep.20215
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发表时间：
2004-06-01
期刊：
影响因子：
13.5
通讯作者：
Hidalgo, R
中科院分区：
文献类型：
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作者：
Andrade, RJ;Lucena, MI;Hidalgo, R
药物性特异性肝病（DIILD）在很大程度上取决于宿主易感因素。小型研究支持人类白细胞抗原（HILA） 11类分子对DIILD易感性的遗传影响。我们寻求HI-A-DRB和-DQB等位基因与DIILD之间的关联，这些等位基因总体上或根据肝损伤的生化表达来考虑。我们共研究了140例确诊或可能诊断为DIILD的患者，根据国际医学科学组织理事会的评估标准，其中635名志愿骨髓和献血者作为对照。基因组扩增后用序列特异性寡核苷酸杂交进行HLA-DRB1*和-DQB1*基因分型。在HLA-DRB和-DQB抗原的分布方面，DIILD组与对照组没有差异。胆固醇淤滞型/混合型肝损害患者的DRB1*15等位基因频率（35.4% vs. 18.6%, P = 0.002；比值比[OR] 2.31）和DQB1*06等位基因频率（61.5% vs. 40.8%, P = 0.001; OR 2.32）明显高于健康者。相比之下，DRB1*07 （16.9% vs. 35.4%; P = 0.003; OR 0.37）和DQB1*02 （32.3% vs. 55.8%; P = 0.003; OR 0.39）等位基因的频率显著降低。总之，任何特定的HI-A等位基因与发生DIILD的倾向之间没有关联。然而，与HLA II类等位基因相关的遗传影响似乎在胆汁淤积/混合性肝毒性中肝损伤的生化表达中发挥作用，并可能解释为什么给定的药物可能导致不同类型的肝损伤。
Drug-induced idiosyncratic liver disease (DIILD) depends largely on host susceptibility factors. Small studies support the genetic influence of human leukocyte antigen (HILA) class 11 molecules on the predisposition to DIILD. We sought associations between HI-A-DRB and -DQB alleles and DIILD considered collectively or according to the biochemical expression of liver damage. We studied a total of 140 patients with a definitive or probable diagnosis of DIILD, as assessed with the Council for International Organizations of Medical Sciences scale, with 635 volunteer bone marrow and blood donors serving as controls. HLA-DRB1* and -DQB1* genotyping was performed by hybridization with sequence-specific oligonucleotides after genomic amplification. The group with DIILD did not differ from control subjects with regard to the distribution of HLA-DRB and -DQB antigens. The frequencies of alleles DRB1*15 (35.4% vs. 18.6% of controls; P =.002; odds ratio [OR] 2.31) and DQB1*06 (61.5% vs. 40.8%; P =.001; OR 2.32) were significantly increased in patients with the cholestatic/mixed type of liver damage in comparison to healthy subjects. By contrast, frequencies of alleles DRB1*07 (16.9% vs. 35.4%; P =.003; OR 0.37) and DQB1*02 (32.3% vs. 55.8%; P =.0003; OR 0.39) were significantly decreased. In conclusion, there is no association between any specific HI-A allele and the propensity to develop DIILD. However, the genetic influence associated with HLA class II alleles appears to play a role in the biochemical expression of liver injury in cholestatic/mixed hepatotoxicity and may explain why a given drug may cause different patterns of liver damage.