Fricke-Galindo I, Jung-Cook H, LLerena A, López-López M
Programa de Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Unidad Xochimilco, Coyoacán, México D.F. , México.
Departamento de Neuropsicofarmacología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Departamento de Farmacia, Universidad Nacional Autónoma de México, Tlalpan, México D.F., México.
Neurologia (Engl Ed). 2018 Apr;33(3):165-176. doi: 10.1016/j.nrl.2015.03.005. Epub 2015 May 11.
Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment since they decrease treatment adherence and impact patients' quality of life of patients. Pharmacogenetics aims to identify genetic polymorphisms associated with drug safety. This article presents a review of genes coding for drug metabolising enzymes and drug transporters, and HLA system genes that have been linked to AED-induced ADRs.
To date, several genetic variations associated with drug safety have been reported: CYP2C92 and 3 alleles, which code for enzymes with decreased activity, have been linked to phenytoin (PHT)-induced neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2 genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles (e.g. HLA-B15:02, -A31:01, -B15:11, -C08:01) with cutaneous ADRs.
Published findings show that there are ADRs with a pharmacogenetic basis and a high interethnic variability, which indicates a need for future studies in different populations to gather more useful results for larger number of patients. The search for biomarkers that would allow predicting ADRs to AEDs could improve pharmacotherapy for epilepsy.
药物不良反应（ADR）是一个重大的公共卫生问题，也是全球发病和死亡的主要原因。就抗癫痫药物（AED）而言，ADR是成功治疗的障碍，因为它们会降低治疗依从性并影响患者的生活质量。药物遗传学旨在识别与药物安全性相关的基因多态性。本文综述了与AED引起的ADR相关的药物代谢酶、药物转运体编码基因以及HLA系统基因。
迄今为止，已报道了几种与药物安全性相关的基因变异：编码活性降低的酶的CYP2C92和3等位基因与苯妥英（PHT）引起的神经毒性有关；GSTM1无效等位基因与卡马西平（CBZ）和丙戊酸（VPA）诱导的肝毒性有关；EPHX1多态性与致畸作用有关；ABCC2基因变异与CBZ和VPA诱导的神经学ADR有关；以及与皮肤ADR相关的HLA等位基因（如HLA-B15:02、-A31:01、-B15:11、-C08:01）。
已发表的研究结果表明，存在具有药物遗传学基础且种族间差异很大的ADR，这表明未来需要在不同人群中开展研究，以便为更多患者收集更有用的结果。寻找能够预测AED引起的ADR的生物标志物可能会改善癫痫的药物治疗。
