title: Measuring pharmacogenetics in special groups: geriatrics.
abstract: BACKGROUND
  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?
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: IRCCS Casa Sollievo della Sofferenza, Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences , San Giovanni Rotondo, Foggia , Italy dseripa@operapadrepio.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.forename: Francesco
authors.initials: F
authors.lastname: Panza
authors.forename: Julia
authors.initials: J
authors.lastname: Daragjati
authors.forename: Giulia
authors.initials: G
authors.lastname: Paroni
authors.forename: Alberto
authors.initials: A
authors.lastname: Pilotto
mesh_terms: D000367:Age Factors; D000368:Aged; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D044127:Epigenesis, Genetic; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D010597:Pharmacogenetics; D010641:Phenotype
chemical_list: D003577:Cytochrome P-450 Enzyme System
keywords: CYP; DNA methylation; epigenetics; geriatrics; pharmacogenetics