Pharmacogenomics in Asian Subpopulations and Impacts on Commonly Prescribed Medications.

Autor: Lo C; Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Nguyen S; College of Pharmacy, Mercer University, Atlanta, Georgia, USA., Yang C; School of Medicine, Stanford University, Palo Alto, California, USA., Witt L; School of Medicine, Stanford University, Palo Alto, California, USA., Wen A; School of Medicine, Stanford University, Palo Alto, California, USA., Liao TV; College of Pharmacy, Mercer University, Atlanta, Georgia, USA., Nguyen J; College of Pharmacy, Mercer University, Atlanta, Georgia, USA., Lin B; Division of Primary Care and Population Health, School of Medicine, Stanford University, Palo Alto, California, USA., Altman RB; Department of Biomedical Data Science, Stanford University, Palo Alto, California, USA.; Department of Biomedical Engineering, Genetics and Medicine, Stanford University, Palo Alto, California, USA., Palaniappan L; Division of Primary Care and Population Health, School of Medicine, Stanford University, Palo Alto, California, USA.
Jazyk: angličtina
Zdroj: Clinical and translational science [Clin Transl Sci] 2020 Sep; Vol. 13 (5), pp. 861-870. Date of Electronic Publication: 2020 Apr 13.
DOI: 10.1111/cts.12771
Abstrakt: Asians as a group comprise > 60% the world's population. There is an incredible amount of diversity in Asian and admixed populations that has not been addressed in a pharmacogenetic context. The known pharmacogenetic differences in Asian subgroups generally represent previously known variants that are present at much lower or higher frequencies in Asians compared with other populations. In this review we summarize the main drugs and known genes that appear to have differences in their pharmacogenetic properties in certain Asian populations. Evidence-based guidelines and summary statistics from the US Food and Drug Administration and the Clinical Pharmacogenetics Implementation Consortium were analyzed for ethnic differences in outcomes. Implicated drugs included commonly prescribed drugs such as warfarin, clopidogrel, carbamazepine, and allopurinol. The majority of these associations are due to Asians more commonly being poor metabolizers of cytochrome P450 (CYP) 2C19 and carriers of the human leukocyte antigen (HLA)-B*15:02 allele. The relative risk increase was shown to vary between genes and drugs, but could be > 100-fold higher in Asians. Specifically, there was a 172-fold increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis with carbamazepine use among HLA-B*15:02 carriers. The effects ranged from relatively benign reactions such as reduced drug efficacy to severe cutaneous skin reactions. These reactions are severe and prevalent enough to warrant pharmacogenetic testing and appropriate changes in dose and medication choice for at-risk populations. Further studies should be done on Asian cohorts to more fully understand pharmacogenetic variants in these populations and to clarify how such differences may influence drug response.
(© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society of Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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