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

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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 wildtype 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.

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