PMID- 32100936 OWN - NLM STAT- MEDLINE DCOM- 20210628 LR - 20240330 IS - 1752-8062 (Electronic) IS - 1752-8054 (Print) IS - 1752-8054 (Linking) VI - 13 IP - 5 DP - 2020 Sep TI - Pharmacogenomics in Asian Subpopulations and Impacts on Commonly Prescribed Medications. PG - 861-870 LID - 10.1111/cts.12771 [doi] AB - 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. CI - (c) 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society of Clinical Pharmacology and Therapeutics. FAU - Lo, Cody AU - Lo C AD - Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. FAU - Nguyen, Samantha AU - Nguyen S AD - College of Pharmacy, Mercer University, Atlanta, Georgia, USA. FAU - Yang, Christine AU - Yang C AD - School of Medicine, Stanford University, Palo Alto, California, USA. FAU - Witt, Lana AU - Witt L AD - School of Medicine, Stanford University, Palo Alto, California, USA. FAU - Wen, Alice AU - Wen A AD - School of Medicine, Stanford University, Palo Alto, California, USA. FAU - Liao, T Vivian AU - Liao TV AD - College of Pharmacy, Mercer University, Atlanta, Georgia, USA. FAU - Nguyen, Jennifer AU - Nguyen J AD - College of Pharmacy, Mercer University, Atlanta, Georgia, USA. FAU - Lin, Bryant AU - Lin B AD - Division of Primary Care and Population Health, School of Medicine, Stanford University, Palo Alto, California, USA. FAU - Altman, Russ B AU - Altman RB AD - Department of Biomedical Data Science, Stanford University, Palo Alto, California, USA. AD - Department of Biomedical Engineering, Genetics and Medicine, Stanford University, Palo Alto, California, USA. FAU - Palaniappan, Latha AU - Palaniappan L AD - Division of Primary Care and Population Health, School of Medicine, Stanford University, Palo Alto, California, USA. LA - eng GR - R01 HL126172/HL/NHLBI NIH HHS/United States GR - K24 HL150476/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review DEP - 20200413 PL - United States TA - Clin Transl Sci JT - Clinical and translational science JID - 101474067 RN - 0 (Anticoagulants) RN - 0 (Anticonvulsants) RN - 0 (Antidepressive Agents) RN - 0 (Antifungal Agents) RN - 0 (Antineoplastic Agents) RN - 0 (Antiviral Agents) RN - 0 (HLA-B*15:02 antigen) RN - 0 (HLA-B15 Antigen) RN - 0 (Platelet Aggregation Inhibitors) RN - EC 1.14.14.1 (CYP2C19 protein, human) RN - EC 1.14.14.1 (Cytochrome P-450 CYP2C19) SB - IM MH - Anticoagulants/administration & dosage/adverse effects/pharmacokinetics MH - Anticonvulsants/administration & dosage/adverse effects/pharmacokinetics MH - Antidepressive Agents/administration & dosage/adverse effects/pharmacokinetics MH - Antifungal Agents/administration & dosage/adverse effects/pharmacokinetics MH - Antineoplastic Agents/administration & dosage/adverse effects/pharmacokinetics MH - Antiviral Agents/administration & dosage/adverse effects/pharmacokinetics MH - Asian People/*genetics MH - Cytochrome P-450 CYP2C19/*genetics/metabolism MH - Global Burden of Disease MH - HLA-B15 Antigen/*genetics MH - Heterozygote MH - Humans MH - Incidence MH - Pharmacogenomic Testing MH - *Pharmacogenomic Variants MH - Platelet Aggregation Inhibitors/administration & dosage/adverse effects/pharmacokinetics MH - Stevens-Johnson Syndrome/*epidemiology/genetics/immunology PMC - PMC7485947 COIS- R.B.A is a board member of Youscript and advisor to Personalis. All other authors declared no competing interests for this work. EDAT- 2020/02/27 06:00 MHDA- 2021/06/29 06:00 PMCR- 2020/09/01 CRDT- 2020/02/27 06:00 PHST- 2019/11/13 00:00 [received] PHST- 2020/01/07 00:00 [accepted] PHST- 2020/02/27 06:00 [pubmed] PHST- 2021/06/29 06:00 [medline] PHST- 2020/02/27 06:00 [entrez] PHST- 2020/09/01 00:00 [pmc-release] AID - CTS12771 [pii] AID - 10.1111/cts.12771 [doi] PST - ppublish SO - Clin Transl Sci. 2020 Sep;13(5):861-870. doi: 10.1111/cts.12771. Epub 2020 Apr 13.