Impact of GATA4 variants on stable warfarin doses in patients with prosthetic heart valves
| Autor: | K E Lee, H Jeong, Hye Sun Gwak, B C Chang, E Jeong |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male medicine.medical_specialty Single-nucleotide polymorphism Pharmacology Gastroenterology Internal medicine Genotype Genetics medicine Humans In patient CYP2C9 Aged Dose-Response Relationship Drug business.industry GATA4 Warfarin Genetic Variation Middle Aged GATA4 Transcription Factor Heart Valve Prosthesis Molecular Medicine Female VKORC1 business Pharmacogenetics medicine.drug |
| Zdroj: | The Pharmacogenomics Journal. 15:33-37 |
| ISSN: | 1473-1150 1470-269X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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