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• W2080240185 startingPage "877" @default.
• W2080240185 abstract "CYP3A4, CYP3A5 and CYP3A7 are hepatic enzymes that metabolize about 50% of drugs on the market, with a large overlap in their specificities. We investigated the genetic bases that contribute to the variation of CYP3A activity.We phenotyped 251 individuals from two independent studies (182 patients treated with methadone and 69 patients with clozapine) for CYP3A activity using the midazolam phenotyping test and genotyped them for CYP3A4, CYP3A5, and CYP3A7 genetic variants, including the single nucleotide polymorphism (SNP) rs4646437C>T in intron 7 of CYP3A4. Owing to the fact that CYP enzymes require electron transfer through the P450 oxidoreductase (POR), and functional impairment has been shown for the POR*28 SNP, this polymorphism was also analysed.We show that CYP3A4, CYP3A5 and CYP3A7 genotypes, including the SNP rs4646437C>T, do not reflect the inter-individual variability of CYP3A activity (P>0.1). In contrast, POR*28 TT genotype presents a 1.6-fold increase in CYP3A activity compared with POR*28C carriers (n = 182, P = 0.004). This finding was replicated in the second independent dataset (n = 69, P = 0.04).The SNP POR*28 seems to be a better genetic marker of the variability of total CYP3A activity in vivo than CYP3A4, CYP3A5 and CYP3A7 genetic variants." @default.
• W2080240185 created "2016-06-24" @default.
• W2080240185 creator A5004418235 @default.
• W2080240185 creator A5007579409 @default.
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• W2080240185 creator A5029157816 @default.
• W2080240185 creator A5072307317 @default.
• W2080240185 date "2009-11-01" @default.
• W2080240185 modified "2023-10-17" @default.
• W2080240185 title "The P450 oxidoreductase genotype is associated with CYP3A activity in vivo as measured by the midazolam phenotyping test" @default.
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• W2080240185 doi "https://doi.org/10.1097/fpc.0b013e32833225e7" @default.
• W2080240185 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19801957" @default.
• W2080240185 hasPublicationYear "2009" @default.
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