内皮型一氧化氮合酶基因多态性与基因相互作用的药物遗传学相关性。
Pharmacogenetic relevance of endothelial nitric oxide synthase polymorphisms and gene interactions.
作者信息
Luizon Marcelo R, Pereira Daniela A, Tanus-Santos Jose E
机构信息
Department of General Biology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais 31270-901, Brazil.
UFMG Graduate Program in Genetics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais 31270-901, Brazil.
出版信息
Pharmacogenomics. 2018 Dec;19(18):1423-1435. doi: 10.2217/pgs-2018-0098. Epub 2018 Nov 6.
Endothelial nitric oxide synthase (NOS3) is a key enzyme responsible for nitric oxide (NO) generation in the vascular endothelium. Endothelial dysfunction is characterized by reduced NO production, and is a hallmark of cardiovascular diseases. Drugs with cardiovascular action may activate NOS3 and result in NO release and vasodilation. Moreover, genetic variations affect NOS3 expression and activity, and may partially explain the variability in the responses to cardiovascular drugs. We reviewed NO signaling and genetic effects on NO formation, and the effects of NOS3 polymorphisms, haplotypes and gene-gene interactions within NO signaling pathways on the responses to cardiovascular drugs. We discuss the role of rare NOS3 variants and further gene-gene interactions analysis for the development of novel therapies for cardiovascular diseases.
内皮型一氧化氮合酶（NOS3）是负责在血管内皮中生成一氧化氮（NO）的关键酶。内皮功能障碍的特征是NO生成减少，是心血管疾病的一个标志。具有心血管作用的药物可能会激活NOS3并导致NO释放和血管舒张。此外，基因变异会影响NOS3的表达和活性，并可能部分解释对心血管药物反应的变异性。我们综述了NO信号传导以及基因对NO形成的影响，以及NO信号通路内NOS3多态性、单倍型和基因-基因相互作用对心血管药物反应的影响。我们讨论了罕见NOS3变异体的作用以及进一步的基因-基因相互作用分析对开发心血管疾病新疗法的意义。
Zotero 插件