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

我们已经建立了一种简单的基因分型方法来检测人类白细胞抗原-A^*3303，它似乎与噻氯匹定引起的严重肝功能障碍有关。在本研究中，我们已经证实了另一个候选基因的多态性，该基因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，人类白细胞抗原-A^*0206和人类白细胞抗原-B^*3901中的一种或两种可能与氯吡格雷所致的肝功能障碍有关。因此，建立了简单的基因分型方法来检测这些特定的HLA等位基因。然后，我们应用这些基因分型方法来确认在第二个人群中，是否有一个或两个HLA等位基因确实与氯吡格雷引起的肝功能障碍有关。然而，没有获得可重复性的结果，可能是由于少数患者患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了噻氯匹定和氯吡格雷所致的肝功能障碍，但尚未确定导致氯吡格雷所致肝功能障碍的致病基因。这些结果表明，替氯匹定和氯吡格雷可以安全地相互替代使用。

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.