TITLE

Farmakogenetika varfarina u kliničkoj praksi

AUTHOR(S)
Božina, Nada
PUB. DATE
April 2010
SOURCE
Biochemia Medica;2010, Vol. 20 Issue 1, p33
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Warfarin is the most widely prescribed oral anticoagulant. It shows great (up to 20-fold) interindividual variability in dose requirement because of both, genetic and environmental factors. Information from pharmacogenomics, a study of the interaction of the individual's genotype and drug response, can help optimize drug efficacy and minimize adverse drug reactions. Genotyping data on two genes, the warfarin metabolic enzyme CYP2C9 and warfarin target enzyme, vitamin K epoxide reductase complex 1 (VKORC1), confirmed their influence on warfarin maintenance dose. Genome-wide association study also found a weak effect of CYP4F2. The presence of CYP2C9*2 or CYP2C9*3 variant alleles, which results in decreased enzyme activity, is associated with a significant decrease in the mean warfarin dose. VKORC1 single nucleotide polymorphisms (SNPs) explain a large fraction of the interindividual variation in warfarin dose, and VKORC1 has an approximately three-fold CVP2C9 effect. Carrier state of a combination of VKORC1 and CVP2C9 polymorphisms, rather than of one of these polymorphisms is associated with severe overanticoagulation. The time to achieve stability is mainly associated with the CYP2C9 genotype. Warfarin resistance has been related to several missense mutations in the VKORC1. Algorithms incorporating genetic (CYP2C9 and VKORC1), demographic, and clinical factors to estimate warfarin dosage could potentially minimize the risk of overdose during warfarin induction.
ACCESSION #
49313488

 

Related Articles

  • Warfarin Dosage Response Related Pharmacogenetics in Chinese Population. Li, Siyue; Zou, Yuangao; Wang, Xia; Huang, Xunbei; Sun, Yong; Wang, Yuqing; Dong, Li; Jiang, Hong // PLoS ONE;Jan2015, Vol. 10 Issue 1, p1 

    Objectives: As the most frequently prescribed anticoagulant, warfarin has large inter-individual variability in dosage. Genetic polymorphisms could largely explain the differences in dosage requirement. rs9923231 (VKORC1), rs7294 (VKORC1), rs1057910 (CYP2C9), rs2108622 (CYP4F2), and rs699664...

  • Pharmacogenetics of Warfarin: Development of a Dosing Algorithm for Brazilian Patients. Perini, J. A.; Struchiner, C. J.; Silva-Assunção, E.; Santana, I. S. C.; Rangel, F.; Ojopi, E. B.; Dias-Neto, E.; Suarez-Kurtz, G. // Clinical Pharmacology & Therapeutics;Dec2008, Vol. 84 Issue 6, p722 

    A dosing algorithm including genetic (VKORC1 and CYP2C9 genotypes) and nongenetic factors (age, weight, therapeutic indication, and cotreatment with amiodarone or simvastatin) explained 51% of the variance in stable weekly warfarin doses in 390 patients attending an anticoagulant clinic in a...

  • Strategies to Enable a Stable Warfarin Maintenance Dose. Gandara, Esteban; Wells, Philip S. // Journal of Coagulation Disorders;2010, Vol. 2 Issue 2, p63 

    In North America, warfarin is the current standard for oral anticoagulation therapy in the treatment and/or prophylaxis of different thrombotic conditions. In daily clinical practice a significant proportion of patients on long-term warfarin therapy fail to stabilize within their target...

  • Pharmacogenetics of warfarin: current status and future challenges. Wadelius, M.; Pirmohamed, M // Pharmacogenomics Journal;2007, Vol. 7 Issue 2, p99 

    Warfarin is an anticoagulant that is difficult to use because of the wide variation in dose required to achieve a therapeutic effect, and the risk of serious bleeding. Warfarin acts by interfering with the recycling of vitamin K in the liver, which leads to reduced activation of several clotting...

  • VKORC1 Gene Analysis of Some Iranian Sensitive Patients to Warfarin. Kianmehr, Z.; Ghadam, P.; Sadrai, S.; Kazemi, B.; Sharifian, R. A. // Pakistan Journal of Biological Sciences;2010, Vol. 13 Issue 18, p906 

    No abstract available.

  • Warfarin Anticoagulant Therapy: A Southern Italy Pharmacogenetics-Based Dosing Model. Mazzaccara, Cristina; Conti, Valeria; Liguori, Rosario; Simeon, Vittorio; Toriello, Mario; Severini, Angelo; Perricone, Corrado; Meccariello, Alfonso; Meccariello, Pasquale; Vitale, Dino Franco; Filippelli, Amelia; Sacchetti, Lucia // PLoS ONE;Aug2013, Vol. 8 Issue 8, p1 

    Background and Aim: Warfarin is the most frequently prescribed anticoagulant worldwide. However, warfarin therapy is associated with a high risk of bleeding and thromboembolic events because of a large interindividual dose-response variability. We investigated the effect of genetic and non...

  • Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients. Choi, Jung Ran; Kim, Jeong-Oh; Kang, Dae Ryong; Yoon, Seong-Ae; Shin, Jung-Young; Zhang, XiangHua; Roh, Mee Ork; Hong, Hyung Joo; Wang, Young-Pil; Jo, Keon-Hyon; Lee, Kwang-Soo; Yun, Ho-Jung; Oh, Yong-Seog; Yoo, Ki-Dong; Jeon, Hee-Gyeong; Lee, Yoon Sook; Kang, Tae Sun; Park, Hyun-Joo; Chung, Myeon Woo; Kang, Jin-Hyoung // Journal of Human Genetics;Apr2011, Vol. 56 Issue 4, p290 

    Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboembolic disorders. We investigated the contribution of genetic variations of four genes and clinical factors to warfarin dose requirement and provided a warfarin-dosing algorithm based on genetic and clinical...

  • Validation of a Rapid and Inexpensive Allele-Specific Amplification (ASA)-PCR Genotyping Assay for Vitamin K Antagonist Pharmacogenomics. Spohn, Gabriele; Geisen, Christof; Luxembourg, Beate; Sittinger, Katja; Seifried, Erhard; Bönig, Halvard // Molecular Diagnosis & Therapy;Jan2011, Vol. 15 Issue 1, p13 

    Background: Variant alleles of vitamin K epoxide reductase complex subunit 1 gene (VKORC1), the target molecule of vitamin K antagonists, and of cytochrome P450 (CYP) 2C9, an enzyme involved in coumarin metabolism, affect the anticoagulant response of coumarins, which have a narrow therapeutic...

  • Effect of age and sex on warfarin dosing. Khoury, Ghada; Sheikh-Taha, Marwan // Clinical Pharmacology;2014, Vol. 6, p103 

    Objective: We examined the potential effect of sex and age on warfarin dosing in ambulatory adult patients. Methods: We conducted a retrospective chart review of patients attending an anticoagulation clinic. We included patients anticoagulated with warfarin for atrial fibrillation or venous...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics