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Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population

Xiaojuan Yan1, Feng Yang2, Hanyun Zhou2

  • 1Department of Respiratory Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, Hubei, China (mainland).

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
|November 20, 2015
PubMed

Insights

Genetic variations in VKORC1 influence warfarin maintenance dose for patients with cardiac valve replacement. Understanding these VKORC1 polymorphisms aids in personalized warfarin therapy.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Clinical Genetics

Background:

  • Vitamin K epoxide reductase complex subunit 1 (VKORC1) plays a crucial role in the vitamin K cycle, essential for blood coagulation.
  • Warfarin, an anticoagulant, requires careful dosage adjustment due to its narrow therapeutic index and inter-individual variability.
  • Single-nucleotide polymorphisms (SNPs) in the VKORC1 gene are known to affect warfarin metabolism and efficacy.

Purpose of the Study:

  • To investigate the association between specific VKORC1 gene polymorphisms (-1639 G/A, 1173 C/T, and 497 T/G) and the required warfarin maintenance dose.
  • To identify genetic factors influencing warfarin dosage in patients undergoing cardiac valve replacement.
  • To explore the correlation of these polymorphisms with clinical characteristics affecting warfarin dose.

Main Methods:

  • A cohort of 298 patients undergoing cardiac valve replacement was studied.
  • Genotyping for VKORC1 polymorphisms ( -1639 G/A, 1173 C/T, and 497 T/G) was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
  • Clinical data, including warfarin maintenance dose, were collected during follow-up.

Main Results:

  • Age, gender, and operation method were significantly correlated with warfarin maintenance dose (P<0.05).
  • VKORC1-1639 G/A AG + GG carriers and VKORC1 1173 C/T CT genotype carriers required significantly higher warfarin maintenance doses compared to AA and TT carriers, respectively (P<0.001).
  • Linear regression confirmed that gender, operation method, heart valve replacement method, and VKORC1 polymorphisms (-1639 G/A and 1173 C/T) were significant predictors of warfarin maintenance dose (P<0.05).

Conclusions:

  • VKORC1 gene polymorphisms are significant genetic determinants of inter-individual variability in warfarin maintenance dose for patients with cardiac valve replacement.
  • Factors such as gender, operation method, and the type of heart valve replacement may also influence warfarin dosage requirements.
  • These findings underscore the importance of pharmacogenetic testing for optimizing warfarin therapy in this patient population.

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