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VKORC1 -1639G/A and 1173 C/T Genetic Polymorphisms Influence Individual Differences in Warfarin Maintenance Dose

Yi Li1, Jun Zhu2, Jianqiang Ding2

  • 11 Department of Pharmacy, Ministry of Health Beijing Hospital , Beijing, People's Republic of China .

Genetic Testing and Molecular Biomarkers
|July 14, 2015
PubMed

Insights

Two VKORC1 gene variations, -1639G/A and 1173C/T, significantly impact warfarin maintenance dosage in valvular heart disease patients post-cardiac valve replacement. Age, gender, and weight also influence dosage requirements.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Genetics

Background:

  • Warfarin is a critical anticoagulant for patients with valvular heart disease (VHD) after cardiac valve replacement (CVR).
  • Individual variability in warfarin maintenance dosage necessitates personalized treatment approaches.
  • The vitamin K epoxide reductase complex subunit 1 (VKORC1) gene is a key determinant of warfarin response.

Purpose of the Study:

  • To investigate the association between two VKORC1 gene polymorphisms, -1639G/A and 1173C/T, and warfarin maintenance dosage in VHD patients.
  • To identify genetic and clinical factors influencing warfarin dose requirements after CVR.

Main Methods:

  • A cohort of 219 VHD patients undergoing warfarin therapy post-CVR was studied.
  • VKORC1 -1639G/A and 1173C/T polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
  • Clinical data including age, gender, weight, and prothrombin time were collected and analyzed statistically.

Main Results:

  • Patients with VKORC1 -1639G/A (AG+GG genotypes) and 1173C/T (CT genotype) polymorphisms required significantly higher warfarin doses.
  • Linear regression revealed that VKORC1 polymorphisms, gender, age, and weight were independently correlated with warfarin maintenance dose.
  • Specific genotype associations demonstrated significant differences in daily warfarin requirements (p<0.001).

Conclusions:

  • VKORC1 -1639G/A and 1173C/T polymorphisms are significant genetic determinants of warfarin maintenance dosage in VHD patients post-CVR.
  • Clinical factors such as gender, age, and weight also play independent roles in warfarin dose individualization.
  • These findings support the integration of pharmacogenetics into warfarin therapy management for improved patient outcomes.
Abstract

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