Dissertation > Excellent graduate degree dissertation topics show

Study on CYP2C9 Polymorphism and Warfarin Dosage Requirement in Population of Han Nationality in China

Author: ZhengCe
Tutor: MeiDan；GuanZuo
School: Peking Union Medical College , China
Course: Pharmacy
Keywords: warfarin enantiomers CYP2C9 polymorphism concentration Dosage INR value
CLC: R96
Type: Master's thesis
Year: 2006
Downloads: 199
Quote: 1
Read: Download Dissertation

Abstract

Warfarin is the most widely prescribed oral anticoagulant for prevention and treatment of pulmonary embolism, venous thrombosis and thromboembolism associated with AF and cardiac valve replacement, for Reducing risk of death, recurrent myocardial infarction, and thrombotic events after AMI. Clinically warfarin is available as a racemic mixture of S- and R-warfarin , and S-warfarin shows 3 to 5 times greater anticoagulation potency than R-warfarin. Cytochrome P-450 2C9(CYP2C9) accounts for nearly complete hepatic metabolism of S-warfarin. Recent studies have shown that CYP2C9*2 and CYP2C9*3—the two important SNPs of CYP2C9, are associated with low maintenance dosage requirement in warfarin therapy and increasing the risk of major bleeding events. In addition, patients with a CYP2C9 variant generally require multiple dosage adjustments and need weeks to months longer to achieve stable warfarin dosing compared to wild-type patients. Yet there have been no extensive and thorough studies in this field in China so far. In this study, the distribution of CYP2C9*2 and *3 of Han nationality in China, the correlation between CYP2C9 genotype, dosage requirements, INR, total and unbound concentration of warfarin enantiomers at steady state were investigated. In this study, a PCR-RFLP method was firstly developed to determine CYP2C9 genotype distribution in warfarin-treated patients, and the result was verified by Direct sequencing analysis. The frequencies of CYP2C9*2 and *3 were 3. 7% and 0. 4%, respectively. In addition, a CYP2C9 variant allele was found in one patient in this study, which disagreed the previous report that there are no CYP2C9*2 alles in Chinese.

Study on CYP2C9 Polymorphism and Warfarin Dosage Requirement in Population of Han Nationality in China

Abstract

Related Dissertations