Development of a system, which can pre-avoid anti-platelet agents-induced severe hepatic disfunction that is difficult to predict

我们开发了一种简单的基因分型方法来检测HLA-A^*3303，它似乎是噻氯匹定引起严重肝功能障碍的原因。在本研究中，我们证实了另一种候选基因多态性，它可能与噻氯匹定引起的肝毒性有关。在我们的初步研究中，我们发现HLA-A^*0206和HLA-B^*3901可能是氯吡格雷诱导的肝功能障碍的原因。因此，开发了检测这些特异性HLA等位基因的简单基因分型方法。然后，我们应用这些基因分型方法来确认HLA等位基因是否与氯吡格雷诱导的第二人群肝功能障碍真正相关。然而，没有得到可重复的结果，可能是由于少数患者有氯吡格雷引起的肝功能障碍。提示不同的遗传因素可能参与噻氯匹定和氯吡格雷引起的肝功能障碍，尽管我们还没有确定导致氯吡格雷引起肝功能障碍的HLA等位基因。提示噻氯匹定与氯吡格雷可作为替代药物安全使用。

We have developed a simple genotyping method to detect HLA-A^*3303, which appeared to be responsible for severe hepatic disfunction induced by ticlopidine. In this study, we have confirmed that another candidate gene polymorphism, which may be involved in ticlopidine-induced hepatotoxicity. We found that either or both HLA-A^*0206 and HLA-B^*3901 may be responsible for clopidogrel-induced hepatic disfunction in our preliminary studies. Thus, simple genotyping methods to detect these specific HLA alleles were developed. Then, we applied these genotyping methods to confirm whether either or both HLA alleles were truly related to the clopidogrel-induced hepatic disfunction in the second population. However, reproducible results were not obtained, possibly due to a small number of patients with clopidogrel-induced hepatic disfunction. It was suggested that different genetic factors may be involved in hepatic disfunction induced by ticlopidine and clopidogrel, although we have not identify the causal HLA allele responsible for clopidogrel-induced hepatic disfunction. These results indicate that ticlopidine and clopidogrel could be used safely as alternative drug each other.