Contribution of CYP2B6 alleles in explaining extreme (S)-methadone plasma levels: a CYP2B6 gene resequencing study.

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Version: author
Serval ID
serval:BIB_B0FCBF667C36
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Contribution of CYP2B6 alleles in explaining extreme (S)-methadone plasma levels: a CYP2B6 gene resequencing study.
Journal
Pharmacogenetics and Genomics
Author(s)
Dobrinas M., Crettol S., Oneda B., Lahyani R., Rotger M., Choong E., Lubomirov R., Csajka C., Eap C.B.
ISSN
1744-6880 (Electronic)
ISSN-L
1744-6872
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
23
Number
2
Pages
84-93
Language
english
Notes
Publication types: JOURNAL ARTICLE
Abstract
BACKGROUND: (S)-Methadone, metabolized mainly by CYP2B6, shows a wide interindividual variability in its pharmacokinetics and pharmacodynamics. METHODS: Resequencing of the CYP2B6 gene was performed in 12 and 35 selected individuals with high (S)-methadone plasma exposure and low (S)-methadone plasma exposure, respectively, from a previously described cohort of 276 patients undergoing methadone maintenance treatment. Selected genetic polymorphisms were then analyzed in the complete cohort. RESULTS: The rs35303484 (*11; c136A>G; M46V) polymorphism was overrepresented in the high (S)-methadone level group, whereas the rs3745274 (*9; c516G>T; Q172H), rs2279344 (c822+183G>A), and rs8192719 (c1294+53C>T) polymorphisms were underrepresented in the low (S)-methadone level group, suggesting an association with decreased CYP2B6 activity. Conversely, the rs3211371 (*5; c1459C>T; R487C) polymorphism was overrepresented in the low-level group, indicating an increased CYP2B6 activity. A higher allele frequency was found in the high-level group compared with the low-level group for rs3745274 (*9; c516G>T; Q172H), rs2279343 (*4; c785A>G; K262R) (together representing CYP2B6*6), rs8192719 (c1294+53C>T), and rs2279344 (c822+183G>A), suggesting their involvement in decreased CYP2B6 activity. These results should be replicated in larger independent cohorts. CONCLUSION: Known genetic polymorphisms in CYP2B6 contribute toward explaining extreme (S)-methadone plasma levels observed in a cohort of patients following methadone maintenance treatment.
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Create date
07/02/2013 18:56
Last modification date
20/08/2019 16:20
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