Cytochrome P450 oxidoreductase genetic polymorphisms A503V and rs2868177 do not significantly affect warfarin stable dosage in Han-Chinese patients with mechanical heart valve replacement.
OBJECTIVE
To investigate the influence of cytochrome P450 oxidoreductase (POR) polymorphisms (A503V and rs2868177) on warfarin stable dosage (WSD) in Han-Chinese patients with mechanical heart valve replacement (MHVR).


METHODS
Three hundred and seventeen Han-Chinese MHVR patients on stable maintenance dose of warfarin were enrolled. Blood samples were collected for genotyping analyses of VKORC1 -1639G>A, CYP2C9 *3, CYP4F2 rs2108622 and POR (A503V and rs2868177). Average WSD of carriers with variant POR genotypes or haplotypes were compared. Association analyses were performed by single and multiple linear regression analysis.


RESULTS
The variant allele frequencies of POR polymorphisms (A503V and rs2868177) were 38.8 % and 44.8 %, respectively. D' between POR A503V and rs2868177 was 0.855, r(2) was 0.375, and the frequencies of the four POR haplotypes were 42.3 % for CG, 36.3 % for TA, 18.9 % for CA, and 2.5 % for TG, respectively. There were no significant differences in average WSD among carriers with three variant POR A503V genotypes or among carriers with three variant POR rs2868177 genotypes (both P > 0.05). Similarly, there were no significant differences in average WSD among carriers with variant POR haplotypes (all P > 0.05). Neither single nor multiple linear regression analyses showed significant effects of POR A503V or POR rs2868177 polymorphisms on WSD.


CONCLUSIONS
POR polymorphisms (A503V and rs2868177) do not appear to significantly influence WSD in Han-Chinese patients with MHVR.
Institute of Clinical Pharmacology, Central South University, Changsha, China, 410078.
Sheng-Lan
SL
Tan
Zhi
Z
Li
Wei
W
Zhang
Guo-Bao
GB
Song
Li-Ming
LM
Liu
Juan
J
Peng
Zhao-Qian
ZQ
Liu
Lan
L
Fan
Xiang-Guang
XG
Meng
Lian-Sheng
LS
Wang
Yao
Y
Chen
Xin-Min
XM
Zhou
Hong-Hao
HH
Zhou
D000925:Anticoagulants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D002681:China; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004247:DNA / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
D000925:Anticoagulants; D014859:Warfarin; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases