Contribution of CYP2B6 alleles in explaining extreme (S)-methadone plasma levels: a CYP2B6 gene resequencing study.
Pharmacogenet Genomics
; 23(2): 84-93, 2013 Feb.
Article
de En
| MEDLINE
| ID: mdl-23249875
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Oxidoreductases, (N-demethylating)
/
Aryl hydrocarbon hydroxylases
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Polymorphisme de nucléotide simple
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Analgésiques morphiniques
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Méthadone
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Troubles liés aux opiacés
Type d'étude:
Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Limites:
Humans
Langue:
En
Journal:
Pharmacogenet Genomics
Sujet du journal:
FARMACOLOGIA
/
GENETICA MEDICA
Année:
2013
Type de document:
Article