Zeng Wu-Tao, Xu Qing, Li Cheng-Hsun, Chen Wei-Yan, Sun Xiu-Ting, Wang Xiang, Yang Yi-Ying, Shi Hui, Yang Zhi-Sheng
The First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan Rd.2, Guangzhou, Guangdong, 510080, People's Republic of China.
The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgangdong Rd, Guangzhou, Guangdong, 510260, People's Republic of China.
Eur J Clin Pharmacol. 2016 Nov;72(11):1327-1334. doi: 10.1007/s00228-016-2098-x. Epub 2016 Aug 4.
The aim of this study was to investigate whether any of the single-nucleotide polymorphisms (SNPs) in the POR gene were significantly associated with CYP activity and expression, and could contribute to the total variability in stable warfarin maintenance doses in Han Chinese.
A total of 408 patients treated at the First Affiliated Hospital of Sun Yat-Sen University were eligible for the study and had attained a stable warfarin maintenance dose at the start of the investigation. Demographics, warfarin maintenance doses, and concomitant medications were documented. Genomic DNA was extracted from peripheral blood samples and genotyped for ten SNPs (CYP 2C9*2 and *3, CYP4F2 rs2108622, VKORC1 -1639C>T, and potential POR genes of rs10239977, rs3815455, rs41301394, rs56256515, rs1057868, and rs2286823) using the Sequenom MassARRAY genotyping system.
A predictive model of warfarin maintenance dose was established and indicated that age, gender, body surface area, aspirin use, CYP2C93, CYP4F2 rs2108622, VKORC1 -1639C>T, and POR37 831-35C>T accounted for 42.4 % of dose variance in patients undergoing anticoagulant treatment. The contribution of POR*37 831-35C>T to warfarin dose variation was only 3.9 %.
For the first time, the SNP POR37 831-35C>T was confirmed as a minor but statistically significant factor associated with interindividual variation in warfarin maintenance dose in Han Chinese. The POR37 gene polymorphism should be considered in future algorithms for faster and more reliable achievement of stable warfarin maintenance doses.
本研究旨在调查POR基因中的任何单核苷酸多态性（SNP）是否与CYP活性和表达显著相关，以及是否有助于汉族患者华法林稳定维持剂量的总体变异性。
中山大学附属第一医院共408例接受治疗的患者符合本研究条件，且在调查开始时已达到华法林稳定维持剂量。记录人口统计学信息、华法林维持剂量和伴随用药情况。从外周血样本中提取基因组DNA，并使用Sequenom MassARRAY基因分型系统对10个SNP（CYP 2C92和3、CYP4F2 rs2108622、VKORC1 -1639C>T以及rs10239977、rs3815455、rs41301394、rs56256515、rs1057868和rs2286823的潜在POR基因）进行基因分型。
建立了华法林维持剂量的预测模型，结果表明年龄、性别、体表面积、阿司匹林使用情况、CYP2C93、CYP4F2 rs2108622、VKORC1 -1639C>T和POR37 831-35C>T占抗凝治疗患者剂量变异的42.4%。POR*37 831-35C>T对华法林剂量变异的贡献仅为3.9%。
首次证实SNP POR37 831-35C>T是与汉族患者华法林维持剂量个体间变异相关的一个次要但具有统计学意义的因素。在未来的算法中应考虑POR37基因多态性，以便更快、更可靠地达到华法林稳定维持剂量。
