Associations of POR polymorphisms and warfarin stable maintenance dose in Han Chinese patients / 中国药理学通报

ABSTRACT

Aim To explore the effect of genetic poly-morphisms of POR on the stable warfarin maintenance doses in Han Chinese patients receiving mechanical heart valve replacement. Methods The association between POR gene polymorphisms and warfarin doses of 185 Han Chinese patients were investigated through ANOVA or t test. SNPs of POR and VKORC1 were de-tected by Sequenom? DNA MassArray genotyping method. CYP2C9*3 was genotyped by polymerase chain reaction-restriction fragment length polymorphism method ( PCR-RFLP ) . Patients ’ clinical characteris-tics, INR value and daily dose were obtained from their medical records. Statistical analysis was performed by SPSS 21. 0 software. Results No mutant carriers of POR rs17148944 , POR rs56256515 and rs72553971 were found in this study. The genotype frequencies of other SNPs were in accordance with Hardy-Weinberg e-quilibrium. In the group of patients with CYP2C9*1*1 , the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(3. 50 ± 1. 07) mg·d-1 vs (3. 14 ± 0. 94) mg· d-1,P =0. 03. Also, in the group of patients with CYP2 C9*1*1 and VKORC1 rs9934438 G allele carri-ers, the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(4. 76 ± 0. 90) mg·d-1 vs (4. 08 ± 1. 03) mg· d-1 ,P=0. 04. No significant difference was found in different genotypes of POR rs2868177 . Conclusion These results illustrate that POR rs17685 T carrier is closely associated with a higher warfarin maintenance dose, suggesting that this SNP is useful for clinical guidance of warfarin.