Impact of GATA4 variants on stable warfarin doses in patients with prosthetic heart valves

Pharmacogenomics J. 2015 Feb;15(1):33-7. doi: 10.1038/tpj.2014.36. Epub 2014 Jul 15.

Abstract

Interindividual variability in stable warfarin doses is largely attributed to VKORC1 and CYP2C9 variants. On the basis of a recent finding of the role of GATA4 in control of CYP2C9 expression, we tested a possible effect of GATA4 genotypes on variability in warfarin response using 201 Korean patients with prosthetic cardiac valves. Two single-nucleotide polymorphisms (SNPs), rs2645400 (G>T) and rs4841588 (G>T), were significantly associated with stable warfarin doses in patients carrying CYP2C9 wild-type homozygotes; homozygote carriers of these two SNPs required higher doses than those with other genotypes (5.94±1.73 versus 5.34±1.88 mg, P=0.026; 5.94±1.66 versus 5.37±1.92, P=0.036, respectively). Multivariate analysis showed that two GATA4 combinations, rs867858 (G>T)/rs10090884 (A>C) and rs2645400 (G>T)/rs4841588 (G>T), increased contribution to the overall warfarin dose variability from 36.4 to 40.9%. This study revealed that GATA4 can be predictive of stable warfarin dose and extended warfarin pharmacogenetics further to the regulation of CYP2C9 expression.

MeSH terms

  • Adult
  • Aged
  • Dose-Response Relationship, Drug
  • Female
  • GATA4 Transcription Factor / genetics*
  • Genetic Variation / drug effects
  • Genetic Variation / genetics*
  • Heart Valve Prosthesis*
  • Humans
  • Male
  • Middle Aged
  • Warfarin / pharmacology*

Substances

  • GATA4 Transcription Factor
  • GATA4 protein, human
  • Warfarin