Besides CYP2C192, the variant allele CYP2C93 is associated with higher on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective coronary stent implantation

被引：78

作者：

Harmsze, Ankie ^{[1
,4
]}

van Werkum, Jochem W. ^{[2
]}

Bouman, Heleen J. ^{[2
]}

Ruven, Henk J. ^{[3
]}

Breet, Nicolien J. ^{[2
]}

Ten Berg, Jurrien M. ^{[2
]}

Hackeng, Christian M. ^{[3
]}

Tjoeng, Mathieu M. ^{[1
]}

Klungel, Olaf H. ^{[4
]}

de Boer, Anthonius ^{[4
]}

Deneer, Vera H. ^{[1
]}

机构：

[1] St Antonius Hosp, Dept Clin Pharm, NL-3430 EM Nieuwegein, Netherlands

[2] St Antonius Hosp, Dept Cardiol, NL-3430 EM Nieuwegein, Netherlands

[3] St Antonius Hosp, Dept Clin Chem, NL-3430 EM Nieuwegein, Netherlands

[4] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Pharmacotherapy, Utrecht, Netherlands

来源：

PHARMACOGENETICS AND GENOMICS | 2010年 / 20卷 / 01期

关键词：

ABCB1; absorption; clopidogrel; coronary stent implantation; CYP2C19; CYP2C9; genes; genetic variations; metabolism; platelet reactivity; OF-FUNCTION POLYMORPHISM; HAPLOTYPE RECONSTRUCTION; ACTIVE METABOLITE; CYP2C19; GENE; RESPONSIVENESS; ACTIVATION; P2Y12; RISK; INTERVENTION;

D O I：

10.1097/FPC.0b013e328333dafe

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Introduction The prodrug, clopidogrel, plays an important role in the prevention of thrombotic events in patients undergoing coronary stenting. However, a substantial number of atherothrombotic events still occur, which can partially be explained by heightened residual platelet reactivity. Several studies report that the genetic variation in CYP2C19 (*2) is associated with an impaired response to clopidogrel. Objectives To evaluate the effect of genetic variants affecting clopidogrel's absorption (ABCB1 C1236T, G2677T/A, C3435T), metabolism (CYP2C9*2, *3, CYP2C19*3, CYP3A4*1B, and CYP3A5*3), and pharmacodynamics (P2Y1 A1622G) on top of the influence of CYP2C19*2 on platelet reactivity in patients undergoing elective coronary stenting on dual antiplatelet therapy. Methods Platelet function was assessed by light transmittance aggregometry and VerifyNow P2Y1 2 assay in 428 consecutive patients. Patients were either on chronic clopidogrel maintenance therapy (75 mg/day for >= 5 days before the intervention) or received a 300 mg clopidogrel loading dose (1-5 days before the intervention, followed by 75 mg/day). Linear and logistic regressions were used to assess the associations between genetic variants and platelet reactivity and poor responder status. Results In both the treatment groups, CYP2C19*2-carriage was associated with higher platelet reactivity (P<0.002) and poor responder status; 75 mg group: adjusted odds ratio (ORadj): 3.8, 95% confidence interval (CI): 2.0-7.2, 300 mg group: ORadj: 4.1, 95% CI: 1.6-10.4. In the 300 mg group, CYP2C9*3-carriage was associated with higher platelet reactivity (P<0.05) and poor responder status (ORadj: 11.1, 95% CI: 1.6-78.8, P= 0.016). Conclusion Besides CYP2C19*2, the variant allele CYP2C9*3 plays an important role in the response to clopidogrel in patients on dual antiplatelet therapy undergoing coronary stenting. Pharmacogenetics and Genomics 20:18-25 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

引用

页码：18 / 25

页数：8

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Besides CYP2C19*2, the variant allele CYP2C9*3 is associated with higher on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective coronary stent implantation

Besides CYP2C192, the variant allele CYP2C93 is associated with higher on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective coronary stent implantation