TY - JOUR
T1 - Influence of NR3C1 and VDR polymorphisms on stable warfarin dose in patients with mechanical cardiac valves
AU - Lee, Kyung Eun
AU - Chung, Jee Eun
AU - Yi, Boram
AU - Cho, Yoon Jeong
AU - Kim, Hyun Jeong
AU - Lee, Gwan Yung
AU - Kim, Joo Hee
AU - Chang, Byung Chul
AU - Gwak, Hye Sun
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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 analyses were 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 ± 2.02 mg) than those with the other genotypic combinations (5.19 ± 1.78 mg, p = 0.034). Multivariate analysis showed that VDR rs7975232/rs2228570 explained 2.0% of the 47.5% variability in overall warfarin 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.
AB - 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 analyses were 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 ± 2.02 mg) than those with the other genotypic combinations (5.19 ± 1.78 mg, p = 0.034). Multivariate analysis showed that VDR rs7975232/rs2228570 explained 2.0% of the 47.5% variability in overall warfarin 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.
KW - Glucocorticoid receptor gene
KW - Number needed to genotype
KW - Single nucleotide polymorphism
KW - Vitamin D receptor gene
KW - Warfarin stable dose
UR - http://www.scopus.com/inward/record.url?scp=85014189339&partnerID=8YFLogxK
U2 - 10.1016/j.ijcard.2017.02.103
DO - 10.1016/j.ijcard.2017.02.103
M3 - Article
C2 - 28262345
AN - SCOPUS:85014189339
SN - 0167-5273
VL - 236
SP - 393
EP - 397
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -