สืบค้นงานวิจัย
Effects of cytochrome P450 2C19 and paraoxonase 1 polymorphisms on antiplatelet response to clopidogrel therapy in patients with coronary artery disease
Tresukosol D. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Effects of cytochrome P450 2C19 and paraoxonase 1 polymorphisms on antiplatelet response to clopidogrel therapy in patients with coronary artery disease
ผู้แต่ง / หัวหน้าโครงการ (EN): Tresukosol D.
บทคัดย่อ (EN): Clopidogrel is an antiplatelet prodrug that is recommended to reduce the risk of recurrent thrombosis in coronary artery disease (CAD) patients. Paraoxonase 1 (PON1) is suggested to be a rate-limiting enzyme in the conversion of 2-oxoclopidogrel to active thiol metabolite with inconsistent results. Here, we sought to determine the associations of CYP2C19 and PON1 gene polymorphisms with clopidogrel response and their role in ADP-induced platelet aggregation. Clopidogrel response and platelet aggregation were determined using Multiplate aggregometer in 211 patients with established CAD who received 75 mg clopidogrel and 75-325 mg aspirin daily for at least 14 days. Polymorphisms in CYP2C19 and PON1 were genotyped and tested for association with clopidogrel resistance. Linkage disequilibrium (LD) and their epistatic interaction effects on ADP-induced platelet aggregation were analysed. The prevalence of clopidogrel resistance in this population was approximately 33.2% (n = 70). The frequencies of CYP2C19∗2 and ∗3 were significantly higher in nonresponder than those in responders. After adjusting for established risk factors, CYP2C19∗2 and ∗3 alleles independently increased the risk of clopidogrel resistance with adjusted ORs 2.94 (95%CI, 1.65-5.26; p<0.001) and 11.26 (95%CI, 2.47- 51.41; p = 0.002, respectively). Patients with ∗2 or ∗3 allele and combined with smoking, diabetes and increased platelet count had markedly increased risk of clopidogrel resistance. No association was observed between PON1 Q192R and clopidogrel resistance (adjusted OR = 1.13, 95%CI, 0.70-1.82; p = 0.622). Significantly higher platelet aggregation values were found in CYP2C19∗2 and ∗3 patients when compared with ∗1/∗1 allele carriers (p = 1.98×10 -6 ). For PON1 Q192R genotypes, aggregation values were similar across all genotype groups (p = 0.359). There was no evidence of gene-gene interaction or LD between CYP2C19 and PON1 polymorphisms on ADP-induced platelet aggregation. Our findings indicated that only CYP2C19∗2 and ∗3 alleles had an influence on clopidogrel resistance. The risk of clopidogrel resistance increased further with smoking, diabetes, and increased platelet count. Copyright © 2014 Tresukosol et al.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-84908211522&doi=10.1371%2fjournal.pone.0110188&partnerID=40&md5=51f4fff1e62155a1f5377c3378c8aa79
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): Ticlopidine
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
หากไม่พบเอกสารฉบับเต็ม (Full Text) โปรดติดต่อหน่วยงานเจ้าของข้อมูล

การอ้างอิง

Tresukosol D.. "Effects of cytochrome P450 2C19 and paraoxonase 1 polymorphisms on antiplatelet response to clopidogrel therapy in patients with coronary artery disease". ไม่ระบุหน่วยงาน. ม.ป.ป.

Tresukosol D.. "Effects of cytochrome P450 2C19 and paraoxonase 1 polymorphisms on antiplatelet response to clopidogrel therapy in patients with coronary artery disease". ไม่ระบุหน่วยงาน. ม.ป.ป.. Print.



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Effects of cytochrome P450 2C19 and paraoxonase 1 polymorphisms on antiplatelet response to clopidogrel therapy in patients with coronary artery disease
Tresukosol D.
มหาวิทยาลัยมหิดล
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