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• W3013772653 abstract "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 < 0.01). Among participants with low‐intermediate and poor CYP2C9 metabolizer genotypes, eight (22%) who also had extensive and rapid CYP2C19 metabolizer genotypes experienced cutaneous adverse events, compared with none of those who also had intermediate CYP2C19 metabolizer genotypes ( P = 0.17). Genetic variation reducing CYP2C9 metabolic activity may increase risk for phenytoin‐induced cutaneous adverse events in the absence of the HLA‐B*15:02 risk allele." @default.
• W3013772653 created "2020-04-03" @default.
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• W3013772653 date "2020-04-18" @default.
• W3013772653 modified "2023-10-18" @default.
• W3013772653 title "Associations of <i>CYP2C9</i> and <i>CYP2C19</i> Pharmacogenetic Variation with Phenytoin‐Induced Cutaneous Adverse Drug Reactions" @default.
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• W3013772653 doi "https://doi.org/10.1111/cts.12787" @default.
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