1. Current Progress in the Pharmacogenetics of Infectious Disease Therapy
- Author
-
Andrew Owen, Emilie R Elliot, and T. Mahungu
- Subjects
Candidate gene ,medicine.medical_specialty ,Future studies ,business.industry ,Human immunodeficiency virus (HIV) ,Pharmacology ,medicine.disease_cause ,Drug development ,Infectious disease (medical specialty) ,Medicine ,Biological plausibility ,Personalized medicine ,business ,Intensive care medicine ,Pharmacogenetics - Abstract
Personalized medicine remains an attractive concept in many areas of medicine, particularly where complex and potentially toxic therapies are prescribed over prolonged periods of time. The inter- and intraindividual variability observed in both therapeutic and toxic effects is governed by demographic, physiological, and genetic factors. The relative contribution of any of these factors to variability differs between populations and prescribed compounds. The completion of the Human Genome Project in 2001 heralded the beginning of great technological advancements in the era of personalized medicine. Over time, and particularly since 2000s, pharmacogenetic studies have utilized either a candidate gene approach or been genome-wide association studies and up to date findings in the fields of HIV, malaria and TB therapies are described in details here. Both these approaches have identified important associations but both also require rigorous clinical validation. This is central to minimizing spurious findings, which have historically led to confusion in the field and have therefore been a barrier to the uptake of pharmacogenetic testing. Spurious associations can also be avoided through thorough mechanistic evaluations to ensure biological plausibility. Understanding mechanisms will also increase the value of the data generated by helping to target future studies and by informing the drug development process. Despite an increase in the number and complexity of studies performed, the clinical utility of reported genotype–phenotype associations remains unclear in many studies. Therefore, there is a need for well-powered validation studies in ethnically diverse cohorts with well-characterized phenotypes.
- Published
- 2017
- Full Text
- View/download PDF