title: Impact of GATA4 variants on stable warfarin doses in patients with prosthetic heart valves.
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.
authors.affiliation: Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea.
authors.forename: E
authors.initials: E
authors.lastname: Jeong
authors.affiliation: 1] Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea [2] College of Pharmacy, Chungbuk National University, Chungbuk, Korea.
authors.forename: K E
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Vismer Co, Ltd, Ansan, Gyeonggi-do, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Jeong
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Yonsei University Medical Center, Seoul, Korea.
authors.forename: B C
authors.initials: BC
authors.lastname: Chang
authors.affiliation: Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Gwak
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics*; D014644:Genetic Variation / Q000187:drug effects / Q000235:genetics*; D006350:Heart Valve Prosthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D014859:Warfarin / Q000494:pharmacology*
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D014859:Warfarin