Institute of Clinical Pharmacology, Central South University, Changsha, China, 410078.
Eur J Clin Pharmacol. 2013 Oct;69(10):1769-75. doi: 10.1007/s00228-013-1544-2. Epub 2013 Aug 16.
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).
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.
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.
POR polymorphisms (A503V and rs2868177) do not appear to significantly influence WSD in Han-Chinese patients with MHVR.
研究细胞色素 P450 氧化还原酶（POR）多态性（A503V 和 rs2868177）对汉族机械心脏瓣膜置换（MHVR）患者华法林稳定剂量（WSD）的影响。
纳入 317 例服用华法林稳定维持剂量的汉族 MHVR 患者。采集血样进行 VKORC1-1639G>A、CYP2C9*3、CYP4F2 rs2108622 和 POR（A503V 和 rs2868177）的基因分型分析。比较携带变异 POR 基因型或单倍型的患者的平均 WSD。采用单因素和多因素线性回归分析进行关联分析。
POR 多态性（A503V 和 rs2868177）的变异等位基因频率分别为 38.8%和 44.8%。POR A503V 和 rs2868177 之间的 D'为 0.855，r(2)为 0.375，4 种 POR 单倍型的频率分别为 CG 型 42.3%、TA 型 36.3%、CA 型 18.9%和 TG 型 2.5%。携带三种变异 POR A503V 基因型或携带三种变异 POR rs2868177 基因型的患者之间的平均 WSD 无显著差异（均 P>0.05）。同样，携带变异 POR 单倍型的患者之间的平均 WSD 也无显著差异（均 P>0.05）。单因素和多因素线性回归分析均未显示 POR A503V 或 POR rs2868177 多态性对 WSD 有显著影响。
POR 多态性（A503V 和 rs2868177）似乎对华法林在汉族 MHVR 患者中的稳定剂量无明显影响。
