Pharmacogenetics and pharmacogenomics: development, science, and translation.
Pharmacogenetics and pharmacogenomics involve the study of the role of inheritance in individual variation in drug response, a phenotype that varies from potentially life-threatening adverse drug reactions to equally serious lack of therapeutic efficacy. This discipline evolved from the convergence of rapid advances in molecular pharmacology and genomics. Originally, pharmacogenetic studies focused on monogenic traits, often involving genetic variation in drug metabolism. However, contemporary studies increasingly involve entire "pathways" encoding proteins that influence both pharmacokinetics--factors that influence the concentration of a drug reaching its target(s)--and pharmacodynamics, the drug target itself, as well as genome-wide approaches. Pharmacogenomics is also increasingly moving across the "translational interface" into the clinic and is being incorporated into the drug development process and the governmental regulation of that process. However, significant challenges remain to be overcome if pharmacogenetics-pharmacogenomics is to achieve its full potential as a major medical application of genomic science.
Weinshilboum
Richard M
RM
Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Mayo Medical School-Mayo Foundation, Rochester, Minnesota 55905, USA. weinshilboum.richard@mayo.edu
Wang
Liewei
L
D015195:Drug Design; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*