Tsareva E Yu, Favorova O O, Boyko A N, Kulakova O G
Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, 117997 Russia.
Mol Biol (Mosk). 2019 Jul-Aug;53(4):574-599. doi: 10.1134/S0026898419040153.
Pharmacogenetics (PG) investigates the inherited variants of the human genome that underlie individual differences in drug metabolic transformation, delivery, and mechanism of action. Not only the contributions of individual genes, but also their cumulative effect should be considered in the case of polygenic diseases, which include the majority of human diseases. Multiple sclerosis (MS) is a severe autoimmune neurodegenerative disorder of the central nervous system (CNS) and is polygenic in nature. Understanding the role that the immune system plays in the pathogenesis of MS helped to design drugs for its pathogenetic therapy. These drugs are known as the disease-modifying treatments (DMTs). Among these are interferon β (IFN-β) and glatiramer acetate (GA), whose treatment efficacy and long-term safety have been proven in many clinical trials. However their efficacy on MS course varies from highly effective to lack of response. Prognostic genetic biomarkers of treatment efficacy can help to identify the MS patient groups where a particular drug is preferential or even strictly indicated to use. The review summarizes the findings from pharmacogenetic studies evaluating the efficacy of IFN-β and GA in MS patients, including the author's original data.
药物遗传学（PG）研究人类基因组的遗传变异，这些变异是药物代谢转化、递送和作用机制个体差异的基础。对于包括大多数人类疾病在内的多基因疾病，不仅要考虑单个基因的作用，还要考虑它们的累积效应。多发性硬化症（MS）是一种严重的中枢神经系统（CNS）自身免疫性神经退行性疾病，本质上是多基因的。了解免疫系统在MS发病机制中的作用有助于设计针对其发病机制的治疗药物。这些药物被称为疾病修正治疗（DMTs）。其中包括干扰素β（IFN-β）和醋酸格拉替雷（GA），它们的治疗效果和长期安全性已在许多临床试验中得到证实。然而，它们对MS病程的疗效从高度有效到无反应不等。治疗效果的预后遗传生物标志物有助于识别特定药物优先甚至严格适用的MS患者群体。本综述总结了评估IFN-β和GA对MS患者疗效的药物遗传学研究结果，包括作者的原始数据。
