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老年人细胞色素 P450(CYP)的遗传药理学。

Pharmacogenetics of cytochrome P450 (CYP) in the elderly.

机构信息

Geriatric Unit & Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, 71013 San Giovanni Rotondo (FG), Italy.

出版信息

Ageing Res Rev. 2010 Oct;9(4):457-74. doi: 10.1016/j.arr.2010.06.001. Epub 2010 Jun 20.

Abstract

The genetics of cytochrome P450 (CYP) is a very active area of multidisciplinary research, overlapping the interest of medicine, biology and pharmacology, being the CYP enzyme system responsible for the metabolism of more than 80% of the commercially available drugs. Variations in CYP encoding genes are responsible for inter-individual differences in CYP production or function, with severe clinical consequences as therapeutic failures (TFs) and adverse drug reactions (ADRs), being ADRs worldwide primary causes of morbidity and mortality in elderly people. In fact, the prevalence of both TFs and ADRs strongly increased in the presence of multiple pharmacological treatments, a common status in subjects aging 65 years and over. The present article explored some basic concepts of human genetics that have important implications in the genetics of CYP. An attempted to transfer these basic concepts to the genetic data reported by the Home Page of The Human Cytochrome P450 (CYP) Allele Nomenclature Committee was also made, focusing on the current knowledge of CYP genetics. The status of what we know and what we need to know is the base for the clinical applications of pharmacogenetics, in which personalized drug treatments constituted the main aim, in particular in patients attending a geriatric ward.

摘要

细胞色素 P450(CYP)的遗传学是一个非常活跃的多学科研究领域,涉及医学、生物学和药理学的交叉领域,CYP 酶系统负责代谢超过 80%的市售药物。CYP 编码基因的变异导致 CYP 产生或功能的个体间差异,具有严重的临床后果,如治疗失败(TFs)和药物不良反应(ADRs),ADRs 是全球老年人发病率和死亡率的主要原因。事实上,在存在多种药物治疗的情况下,TFs 和 ADRs 的患病率都强烈增加,这在 65 岁及以上的人群中是常见的状况。本文探讨了一些人类遗传学的基本概念,这些概念对 CYP 的遗传学有重要影响。还尝试将这些基本概念转化为人类细胞色素 P450(CYP)等位基因命名委员会主页报告的遗传数据,重点介绍 CYP 遗传学的现有知识。我们所知道的和需要知道的现状是药物遗传学临床应用的基础,其中个体化药物治疗是主要目标,特别是在老年病房的患者中。

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