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Influence of NR3C1 and VDR polymorphisms on stable warfarin dose in patients with mechanical cardiac valves

Title
Influence of NR3C1 and VDR polymorphisms on stable warfarin dose in patients with mechanical cardiac valves
Author
정지은
Keywords
Vitamin D receptor gene; Glucocorticoid receptor gene; Single nucleotide polymorphism; Warfarin stable dose; Number needed to genotype; VITAMIN-D-RECEPTOR; NUCLEAR RECEPTORS; GLUCOCORTICOID SENSITIVITY; TRANSCRIPTIONAL REGULATION; GENETIC POLYMORPHISMS; DEPRESSIVE DISORDER; JAPANESE PATIENTS; CYP2C9 GENOTYPE; HEART-DISEASE; HAN CHINESE
Issue Date
2017-06
Publisher
ELSEVIER IRELAND LTD
Citation
INTERNATIONAL JOURNAL OF CARDIOLOGY, v. 236, Page. 393-397
Abstract
Objectives: The aim of this study was to evaluate the associations between polymorphisms of VKORC1, CYP2C9, CYP4F2, NR3C1 and VDR genes and stable warfarin doses in Korean patients with mechanical heart valves. Methods: Seventeen single-nucleotide polymorphisms (SNPs) in 204 patients with stable warfarin dose were analyzed: VKORC1 (rs9934438), CYP2C9 (rs1057910), CYP4F2 (rs2108622), NR3C1 (rs41423247, rs1800445, rs56149945, rs10052957, rs6198, rs33388, rs6196, and rs244465), and VDR (rs1544410, rs11568820, rs731236, rs757343, rs7975232, and rs2228570). Statistical analyseswere conducted to evaluate the associations of gene variations with stable warfarin dose. Number needed to genotype was obtained by calculating the percentage of patients whose predicted dose was at least 20% higher or lower than the actual stable dose. Results: The combined genotypes of rs7975232 and rs2228570 of the VDR gene revealed a significant association with stable warfarin dose, along with VKORC1, CYP2C9, and CYP4F2 polymorphisms. Patients with the genotype combination GT, TT/CT, CC of VDR rs7975232/rs2228570 required significantly higher stable warfarin dose (5.79 +/- 2.02mg) than those with the other genotypic combinations (5.19 +/- 1.78mg, p= 0.034). Multivariate analysis showed that VDR rs7975232/rs2228570 explained 2.0% of the 47.5% variability in overallwarfarin dose. Adding VDR SNP combinations to the base model including non-genetic variables (age, sex, and body weight) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 41. Conclusions: This study showed that stable warfarin dose is associated with VDR SNPs along with VKORC1, CYP2C9, and CYP4F2 SNPs. (C) 2017 Elsevier B.V. All rights reserved.
URI
https://www.internationaljournalofcardiology.com/article/S0167-5273(16)32463-9/abstracthttp://repository.hanyang.ac.kr/handle/20.500.11754/72124
ISSN
0167-5273; 1874-1754
DOI
10.1016/j.ijcard.2017.02.103
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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