NDLI: Influence of CYP2C19 loss-of-function variants on the metabolism of clopidogrel in patients from north-western China.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lin, R. Zhang, L. Zhang, P. Zhou, L. Liu, T. Li, Y. Zhang, W. Wang, W. Zhang, J.
Spatial Coverage	China
Description	Country affiliation: China Author Affiliation: Lin R ( School of Pharmacology, Health Science Center, Xi'an Jiaotong University, Xi'an, China.)
Abstract	WHAT IS KNOWN AND OBJECTIVE: Variation of the cytochrome P450 2C19 gene coding for the CYP2C19 enzyme has been reported to be associated with clopidogrel response variability. The activity of the CYP2C19 enzyme is genetically influenced by polymorphisms of its gene. METHODS: This study was conducted to assess the impact of CYP2C19 polymorphism on the clopidogrel metabolism, indirectly selecting the plasma concentration ratios of clopidogrel to its inactive metabolite SR26334 as an evaluation index. Genotyping and plasma concentration results of 366 patients on clopidogrel maintenance therapy (75 mg daily dose) were analysed in this study. CYP2C19 genotypes were determined by PCR-restriction fragment length polymorphism method. RESULTS AND DISCUSSION: As for CYP2C19, patients were classified into three metabolism genotype groups: EM (44·3%), IM (43·4%) and PM (12·3%). The mean plasma concentration ratio of clopidogrel to its inactive metabolite SR26334 for the entire sample was 0·507. The plasma concentration ratios of the 3 metabolism groups were significantly different (P < 0·001). The lowest plasma concentration ratio value was observed for PM patients. WHAT IS NEW AND CONCLUSION: Polymorphism of CYP2C19 was significantly associated with plasma concentration ratios of clopidogrel to its inactive metabolite SR26334. Clopidogrel metabolism was regulated by CYP2C19. The 2 and 3 allele carriage were independently associated with the antiplatelet effect of chronic clopidogrel therapy.
File Format	HTM / HTML
ISSN	02694727
Issue Number	3
Volume Number	40
e-ISSN	13652710
Journal	Journal of Clinical Pharmacy and Therapeutics
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2015-06-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Therapeutics Discipline Pharmacology Cytochrome P-450 Cyp2c19 Genetics Platelet Aggregation Inhibitors Pharmacokinetics Ticlopidine Analogs & Derivatives Aged Asian Continental Ancestry Group China Metabolism Female Genotype Humans Male Middle Aged Polymerase Chain Reaction Polymorphism, Genetic Polymorphism, Restriction Fragment Length Blood Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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