کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6002769 | 1182980 | 2011 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacogenomics of clopidogrel: Evidence and perspectives
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کلمات کلیدی
VASPCyPPPICYP2C19PON1ADPPCIcAMP - cAMPadenosine diphosphate - آدنوزین دی فسفاتCyclic adenosine monophosphate - آدنوزین مونوفسفات CyclicAntiplatelet therapy - آنتی بادی درمانCytochrome P450 - سیتوکروم پی۴۵۰Pharmacogenomics - فارماکوژنومیکconfidence interval - فاصله اطمینانVasodilator-stimulated phosphoprotein - فسفوپروتئین تحریک شده با واسوادولاتورpercutaneous coronary intervention - مداخله کرونری از راه پوستProton-pump inhibitors - مهار کننده های پمپ پروتونodds ratio - نسبت شانس هاParaoxonase-1 - پاراکسوناز-1clopidogrel - کلوپیدوگرل
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Clopidogrel has become the mainstay oral antiplatelet regimen to prevent recurrent ischemic events after acute coronary syndromes or stent placement. However, there is marked interindividual variability in the antiplatelet effects of clopidogrel, and a reduced response to this drug may be a risk factor for ischemic complications. Pharmacogenomic analyses, including candidate-gene and genome-wide association studies, have confirmed that genetic polymorphisms in the hepatic cytochrome P450 (CYP) 2C19 dominantly affect the antiplatelet effects of clopidogrel. CYP2C19 reduced-function alleles have been associated with a significant decrease in clopidogrel responsiveness and a higher risk of adverse cardiac events including stent thrombosis, myocardial infarction, and death in several prospective studies, although these effects were not reproduced in a recent large randomized study that included a randomized control group. The US Food and Drug Administration addressed this issue by adding a boxed warning to the clopidogrel label and suggesting that adjusting the clopidogrel dose or using alternative antiplatelet agents should be potentially implemented for high-risk individuals who are identified based on the CYP2C19 genotype. Although it is promising that CYP2C19 genotyping could be used to guide personalized antiplatelet clopidogrel therapy, currently there is insufficient evidence to recommend routine genetic testing. Prospective randomized clinical trials are necessary to validate this pharmacogenomic approach to clopidogrel therapy. In the most recent trial, paraoxonase-1 (PON1) was identified as a crucial new enzyme for clopidogrel bioactivation, with its common Q192R polymorphism determining the rate of active metabolite and the clinical activity of clopidogrel. Further studies are needed to investigate the comprehensive influence of a number of different polymorphisms of CYP2C19 and PON1 variant alleles or other genetic variants on clopidogrel in various ethnic populations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Thrombosis Research - Volume 128, Issue 4, October 2011, Pages 307-316
Journal: Thrombosis Research - Volume 128, Issue 4, October 2011, Pages 307-316
نویسندگان
Tong Yin, Toshiyuki Miyata,