Seripa Davide, Panza Francesco, Daragjati Julia, Paroni Giulia, Pilotto Alberto
IRCCS Casa Sollievo della Sofferenza, Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences , San Giovanni Rotondo, Foggia , Italy
Expert Opin Drug Metab Toxicol. 2015 Jul;11(7):1073-88. doi: 10.1517/17425255.2015.1041919. Epub 2015 May 19.
The cytochrome P450 (CYP) enzymes oxidize about 80% of the most commonly used drugs. Older patients form a very interesting clinical group in which an increased prevalence of adverse drug reactions (ADRs) and therapeutic failures (TFs) is observed. Might CYP drug metabolism change with age, and justify the differences in drug response observed in a geriatric setting?
A complete overview of the CYP pharmacogenetics with a focus on the epigenetic CYP gene regulation by DNA methylation in the context of advancing age, in which DNA methylation might change.
Responder phenotypes consist of a continuum spanning from ADRs to TFs, with the best responders at the midpoint. CYP genetics is the basis of this continuum on which environmental and physiological factors act, modeling the phenotype observed in clinical practice. Physiological age-related changes in DNA methylation, the main epigenetic mechanisms regulating gene expression in humans, results in a physiological decrease in CYP gene expression with advancing age. This may be one of the physiological changes that, together with increased drug use, contributed to the higher prevalence of ADRs and TFs observed in the geriatric setting, thus, making geriatrics a special group for pharmacogenetics.
细胞色素P450（CYP）酶可氧化约80%最常用的药物。老年患者构成了一个非常有趣的临床群体，在该群体中观察到药物不良反应（ADR）和治疗失败（TF）的发生率增加。CYP药物代谢会随年龄变化吗？这能否解释在老年患者中观察到的药物反应差异？
对CYP药物遗传学进行全面概述，重点关注在年龄增长过程中DNA甲基化对CYP基因的表观遗传调控，其中DNA甲基化可能会发生变化。
反应者表型构成了一个从ADR到TF的连续统一体，最佳反应者处于中间位置。CYP遗传学是这个连续统一体的基础，环境和生理因素作用于其上，塑造了临床实践中观察到的表型。DNA甲基化是调节人类基因表达的主要表观遗传机制，与年龄相关的生理变化会导致CYP基因表达随年龄增长而生理性下降。这可能是导致老年患者中ADR和TF发生率较高的生理变化之一，老年患者用药增多，因此，老年医学成为药物遗传学的一个特殊群体。
