Effects of single nucleotide polymorphisms in c-Myc on stable warfarin doses in patients with cardiac valve replacements

Pharmacogenomics. 2015;16(10):1101-8. doi: 10.2217/pgs.15.37. Epub 2015 Aug 7.

Abstract

Aim: This study aimed to investigate an association between c-Myc SNPs and stable warfarin doses.

Materials & methods: The influences of genetic polymorphisms on dose requirements were investigated by genotyping ten SNPs in 201 patients with stable warfarin doses; VKORC1 (rs9923231), CYP2C9 (rs1057910), CYP4F2 (rs2108622), GATA4 (rs10090884), c-Myc (rs4645962, rs4645943, rs4645948 and rs4645974) and 8q24 (rs1447295 and rs16901979).

Results: Around 44.3% of the overall interindividual variability in warfarin dose requirements was explained by the multivariate regression model; VKORC1 genotype accounted for 26.4%, CYP2C9 genotype for 4.9%, age for 3.4%, c-Myc genotypes for 5.2% (rs4645974 for 2.4% and rs4645943 for 2.8%), CYP4F2 genotype for 2.9% and diuretic use for 1.5%.

Conclusion: Our results revealed that c-Myc could be a determinant of stable warfarin doses.

Keywords: 8q24; VKORC1; c-Myc; transcription factor; warfarin.

MeSH terms

  • Anticoagulants / administration & dosage*
  • Cytochrome P-450 Enzyme System / genetics
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Heart Valve Prosthesis
  • Heart Valves / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Proto-Oncogene Proteins c-myc / genetics*
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin / administration & dosage*

Substances

  • Anticoagulants
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Warfarin
  • Cytochrome P-450 Enzyme System
  • Vitamin K Epoxide Reductases