Pharmacogenetics: The Influence of Genetic Variation on Drug Efficacy and Toxicity
Genetic polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and receptors contribute, at least in part, to the wide interindividual variability in drug response and adverse drug reactions. Pharmacogenetics is the study of the influence of genetic variation on drug efficacy or toxicity, focusing on single genes. The term is often used interchangeably with pharmacogenomics, which is the study of how genetic makeup affects an individual’s response to drugs; in other words, the focus is on many genes. Pharmacogenetics can be broadly divided into (1) the study of genetic variations that affect drug metabolism (pharmacokinetics); and (2) the study of genetic variations that affect drug targets (pharmacodynamics).
Thus far, some small-scale studies have demonstrated an association between various genotypes or haplotypes and response to drug therapies for 2 major eye disorders, age-related macular degeneration and glaucoma, but the results are conflicting. One example is the relationship between single nucleotide polymorphisms (SNPs) in genes and the response to latanoprost, specifically, SNPs in the genes coding for matrix metalloproteinases and SNPs in the prostaglandin F2α receptor gene (PTGFR). Another example is the pharmacogenetic relationship between polymorphisms in specific genes and the different levels of drug efficacy in the treatment of exudative age-related macular degeneration.
Although translation of pharmacogenetic and pharmacogenomic data into clinical practice would provide significant opportunities to increase the safety and efficacy of pharmacotherapy, consensus (social, ethical, and economical) on issues such as genetic discrimination needs to be reached and such issues addressed by regulatory agencies. Clinicians must be aware of the ethical, legal, and social issues associated with genetic testing.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.