Measuring pharmacogenetics in special groups: geriatrics

Abstract

Introduction: 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?

Areas covered: 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.

Expert opinion: 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.

Keywords:

• CYP
• DNA methylation
• epigenetics
• geriatrics
• pharmacogenetics

Declaration of interest

This work was completely supported by “Ministero della Salute”, IRCCS Research Program, Ricerca Corrente 2015-2017, Linea n. 2 “Malattie complesse e terapie innovative” and by the “5 × 1000” voluntary contribution. The authors have no conflict of interest to disclose.

Notes

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