The role of epigenetics in personalized medicine: challenges and opportunities.
Bottom Line: These alterations include methylation, acetylation, phosphorylation, and ubiquitylation of DNA and histone proteins (nucleosomes) as well as chromatin remodeling.DNA methylation is one important modification that leads to disease.This review will discuss the advances that have been made as well as the challenges for the future.
Epigenetic alterations are considered to be very influential in both the normal and disease states of an organism. These alterations include methylation, acetylation, phosphorylation, and ubiquitylation of DNA and histone proteins (nucleosomes) as well as chromatin remodeling. Many diseases, such as cancers and neurodegenerative disorders, are often associated with epigenetic alterations. DNA methylation is one important modification that leads to disease. Standard therapies are given to patients; however, few patients respond to these drugs, because of various molecular alterations in their cells, which may be partially due to genetic heterogeneity and epigenetic alterations. To realize the promise of personalized medicine, both genetic and epigenetic diagnostic testing will be required. This review will discuss the advances that have been made as well as the challenges for the future.
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Mentions: To understand variable drug responses (traditional and/or personalized medicines), pharmacokinetics (PK) and pharmacodynamics (PD) are highly useful. These two disciplines integrate quantitative measurements of drug exposure and effect (figure 2). Pharmacokinetics data are associated with drug exposure and the monitoring of drug levels, providing a platform to analyze the phenotypic markers (epigenetic markers) useful for personalized medicine. Variability in drug response is often linked to alterations or mutations in the drug metabolizing enzymes cytochrome P450 and glucuronyl transferase, encoded by the polymorphic genes of the CYP450 family , as well as drug transporters encoded by several hundred genes . Microarray technology can be used to detect the 29 known variants of two important CYP450 genes, CYP2D6 and CYP2C19; these genes affect the metabolism of 25% of all prescribed drugs .