Challenges to assess substrate-dependent allelic effects in CYP450 enzymes and the potential clinical implications.
Pharmacogenomics J
; 19(6): 501-515, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31616046
ABSTRACT
Cytochrome P450 enzyme variant alleles have shown evidence that functional consequences differ between substrates. A systematic effort has not yet been made to confirm substrate-dependent activity. This review will discuss the challenges of assessing three examples (CYP2C8*3, CYP2D6*10, and CYP2C9*2) where substrate-dependent activity has been hypothesized with differing levels of evidence and their potential clinical implications. Data supports bidirectional substrate-dependent activity for CYP2C8*3. Although some data suggests CYP2D6*10 causes differences in the magnitude of effect across substrates, confirmatory studies are needed. Convincing evidence for CYP2C9*2 was lacking likely due to compensatory CYP450 metabolism or experimental variability. Confirmed substrate-dependent activity has the potential to impact clinical use of pharmacogenomics, and must be taken into consideration to ensure the goal of improving treatment through personalization is met. It is important for the pharmacogenomics community to begin thinking about this important topic and how it can be best accommodated in clinical practice.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistema Enzimático do Citocromo P-450
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article