Associations of CYP2C9 and CYP2C19 Pharmacogenetic Variation with Phenytoin‐Induced Cutaneous Adverse Drug Reactions
| Autor: | Brian L Lawson, Allan E. Rettie, Vincent X. Liu, Dilrini K. Ranatunga, Alison E. Fohner, Catherine Schaefer, Khanh K. Thai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
030213 general clinical medicine medicine.medical_specialty Pharmacogenomic Variants CYP2C19 HLA-B15 Antigen Risk Assessment 030226 pharmacology & pharmacy Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Risk Factors Internal medicine medicine Humans Genetic Predisposition to Disease General Pharmacology Toxicology and Pharmaceutics Allele Adverse effect CYP2C9 Alleles Aged Cytochrome P-450 CYP2C9 Retrospective Studies Aged 80 and over Molecular Epidemiology business.industry Research General Neuroscience lcsh:Public aspects of medicine lcsh:RM1-950 lcsh:RA1-1270 Articles General Medicine Odds ratio Middle Aged Pharmacogenomic Testing Cytochrome P-450 CYP2C19 lcsh:Therapeutics. Pharmacology Genetic epidemiology Phenytoin Cohort Female Drug Eruptions business Pharmacogenetics |
| Zdroj: | Clinical and Translational Science, Vol 13, Iss 5, Pp 1004-1009 (2020) Clinical and Translational Science |
| ISSN: | 1752-8054 1752-8062 |
| Popis: | The role of cytochrome P450 (CYP)2C9 and CYP2C19 genetic variation in risk for phenytoin‐induced cutaneous adverse drug events is not well understood independently of the human leukocyte antigen B (HLA‐B)*15:02 risk allele. In the multi‐ethnic resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, we identified 382 participants who filled a phenytoin prescription between 2005 and 2017. These participants included 21 people (5%) who self‐identified as Asian, 18 (5%) as black, 29 (8%) as white Hispanic, and 308 (81%) as white non‐Hispanic. We identified 264 (69%) CYP2C9*1/*1, 77 (20%) CYP2C9*1/*2, and 29 (8%) CYP2C9*1/*3. We also determined CYP2C19 genotypes, including 112 with the increased activity CYP2C19*17 allele. Using electronic clinical notes, we identified 32 participants (8%) with phenytoin‐induced cutaneous adverse events recorded within 100 days of first phenytoin dispensing. Adjusting for age, sex, daily dose, and race/ethnicity, participants with CYP2C9*1/*3 or CYP2C9*2/*2 genotypes were more likely to develop cutaneous adverse events compared with CYP2C9*1/*1 participants (odds ratio 4.47; 95% confidence interval 1.64–11.69; P |
| Databáze: | OpenAIRE |
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