Cardiovascular Pharmacogenetics: From Discovery of Genetic Association to Clinical Adoption of Derived Test.

Autor:	Delabays B; Canada Excellence Research Chair in Genomic Medicine, Victor Phillip Dahdaleh Institute of Genomic Medicine, Department of Human Genetics, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada (B.D., K.T., V.M.); and Medeloop Inc., Palo Alto, California, and Montreal, QC, Canada (J.W.)., Trajanoska K; Canada Excellence Research Chair in Genomic Medicine, Victor Phillip Dahdaleh Institute of Genomic Medicine, Department of Human Genetics, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada (B.D., K.T., V.M.); and Medeloop Inc., Palo Alto, California, and Montreal, QC, Canada (J.W.)., Walonoski J; Canada Excellence Research Chair in Genomic Medicine, Victor Phillip Dahdaleh Institute of Genomic Medicine, Department of Human Genetics, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada (B.D., K.T., V.M.); and Medeloop Inc., Palo Alto, California, and Montreal, QC, Canada (J.W.)., Mooser V; Canada Excellence Research Chair in Genomic Medicine, Victor Phillip Dahdaleh Institute of Genomic Medicine, Department of Human Genetics, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada (B.D., K.T., V.M.); and Medeloop Inc., Palo Alto, California, and Montreal, QC, Canada (J.W.) vincent.mooser@mcgill.ca.
Jazyk:	angličtina
Zdroj:	Pharmacological reviews [Pharmacol Rev] 2024 Aug 15; Vol. 76 (5), pp. 791-827. Date of Electronic Publication: 2024 Aug 15.
DOI:	10.1124/pharmrev.123.000750
Abstrakt:	Recent breakthroughs in human genetics and in information technologies have markedly expanded our understanding at the molecular level of the response to drugs, i.e., pharmacogenetics (PGx), across therapy areas. This review is restricted to PGx for cardiovascular (CV) drugs. First, we examined the PGx information in the labels approved by regulatory agencies in Europe, Japan, and North America and related recommendations from expert panels. Out of 221 marketed CV drugs, 36 had PGx information in their labels approved by one or more agencies. The level of annotations and recommendations varied markedly between agencies and expert panels. Clopidogrel is the only CV drug with consistent PGx recommendation (i.e., "actionable"). This situation prompted us to dissect the steps from discovery of a PGx association to clinical translation. We found 101 genome-wide association studies that investigated the response to CV drugs or drug classes. These studies reported significant associations for 48 PGx traits mapping to 306 genes. Six of these 306 genes are mentioned in the corresponding PGx labels or recommendations for CV drugs. Genomic analyses also highlighted the wide between-population differences in risk allele frequencies and the individual load of actionable PGx variants. Given the high attrition rate and the long road to clinical translation, additional work is warranted to identify and validate PGx variants for more CV drugs across diverse populations and to demonstrate the utility of PGx testing. To that end, pre-emptive PGx combining genomic profiling with electronic medical records opens unprecedented opportunities to improve healthcare, for CV diseases and beyond. SIGNIFICANCE STATEMENT: Despite spectacular breakthroughs in human molecular genetics and information technologies, consistent evidence supporting PGx testing in the cardiovascular area is limited to a few drugs. Additional work is warranted to discover and validate new PGx markers and demonstrate their utility. Pre-emptive PGx combining genomic profiling with electronic medical records opens unprecedented opportunities to improve healthcare, for CV diseases and beyond. (Copyright © 2024 by The Author(s).)
Databáze:	MEDLINE
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