Measuring pharmacogenetics in special groups: geriatrics

Abstract

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.

Heat stress: A risk factor for skin carcinogenesis

“…If melanin is produced and distributed correctly, keratinocytes are protected from the harmful effects of UV, even as the cell is undergoing cell division (Seripa et al, 2015;Tallmadge et al, 2015;Wilken et al, 2015). However, if the melanin production and distribution is significantly reduced, or if alterations in the signalling pathways of the keratinocyte-melanocyte complex arise, leading to diminished melanin production, then it is possible for UV and other environmental stresses to cause the DNA mutations that precede skin cancers .…”

The role of epigenomics in personalized medicine

“…Epigenetic alterations may be a better indicator than chronological age for personalizing drug therapy for the older population. For example, it has been proposed that epigenetic regulation of cytochrome P450 (CYP) enzymes responsible for drug metabolism through DNA methylation may result in altered drug exposure in geriatric patients [119]. More research is needed to elucidate the relationships between epigenetics and drug exposure and response during senescence, but is a promising alternative to chronologic age for adjusting pharmacotherapy in older adults.…”

DNA Methylation of ADME Genes

“…Independent from other factors, there is first evidence that differences in DNA methylation patterns may contribute to the ontogeny of the expression of DME in childhood . A higher risk for ADRs is well established in older patients, which may not only be related to, e.g., different body composition and impaired organ function due to underlying diseases as well as polypharmacy, but also to the reduced capability to metabolize and/or transport drugs . Major research activities are warranted to fully comprehend the impact of DNA methylation on ADME gene expression and function related to these different subgroups.…”

“…to metabolize and/or transport drugs. 16 Major research activities are warranted to fully comprehend the impact of DNA methylation on ADME gene expression and function related to these different subgroups.…”