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Association Between the Lower Extremity Deep Venous Thrombosis, the Warfarin Maintenance Dose, and CYP2C9*3,

Shang Ju1, Yu Gao1, Xin Cao1

  • 1Department of Peripheral Vascular, Beijing University of Chinese Medicine Dongzhimen Hospital , Beijing, China .

Genetic Testing and Molecular Biomarkers
|September 6, 2017
PubMed

Insights

Genetic variations in CYP3A5*3 may increase the risk of lower extremity deep venous thrombosis (LEDVT). These genetic factors, along with CYP2C9*3 and CYP2D6*10, also influence warfarin maintenance dosage.

Area of Science:

  • Pharmacogenomics
  • Thrombosis Research
  • Clinical Genetics

Background:

  • Lower extremity deep venous thrombosis (LEDVT) is a significant postsurgical complication.
  • Warfarin is a commonly prescribed anticoagulant, but its dosage requires careful management.
  • Genetic polymorphisms in drug-metabolizing enzymes can influence drug efficacy and patient outcomes.

Purpose of the Study:

  • To investigate the association between CYP2C9*3, CYP2D6*10, and CYP3A5*3 genetic polymorphisms and the risk of LEDVT.
  • To explore the relationship between these genetic polymorphisms and the required warfarin maintenance dose in LEDVT patients.

Main Methods:

  • A case-control study involving 536 LEDVT patients and 540 controls.
  • Genotyping of CYP2C9*3, CYP2D6*10, and CYP3A5*3 alleles using PCR-RFLP.
  • Analysis of genotype distributions and haplotype frequencies using SHEsis software.
  • Logistic regression analysis to identify risk and protective factors for LEDVT.

Main Results:

  • Increased frequency of CYP3A5*3 genotypes (A/G, G/G) and the G allele in the LEDVT group.
  • Higher ACG haplotype frequency and lower ACA/ATA haplotype frequencies in LEDVT patients.
  • CYP3A5*3 and the ACG haplotype identified as independent risk factors for LEDVT.
  • CYP2C9*3, CYP2D6*10, and CYP3A5*3 polymorphisms were linked to warfarin maintenance dose variations.

Conclusions:

  • CYP3A5*3 genetic polymorphism is a potential risk factor for LEDVT.
  • CYP2C9*3, CYP2D6*10, and CYP3A5*3 genetic variations are associated with warfarin maintenance dosage, highlighting their pharmacogenetic importance.
Abstract

Keywords:
CYP2C9*3CYP2D6*10CYP3A5*3genetic polymorphismlower extremity deep venous thrombosismaintenance doseriskwarfarin

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