Influence of genetic polymorphisms in cytochrome P450 oxidoreductase on the variability in stable warfarin maintenance dose in Han Chinese
Influence of genetic polymorphisms in cytochrome P450 oxidoreductase on the variability in stable warfarin maintenance dose in Han Chinese
复制标题
汉族细胞色素P450氧化还原酶基因多态性对华法林稳定维持剂量变异性的影响
DOI：
10.1007/s00228-016-2098-x
复制
发表时间：
2016-11-01
影响因子：
2.9
通讯作者：
Yang, Zhi-Sheng
中科院分区：
文献类型：
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作者：
Zeng, Wu-Tao;Xu, Qing;Yang, Zhi-Sheng
目的本研究的目的是探讨POR基因中的单核苷酸多态性(SNP)是否与CYP活性和表达显着相关，并可能影响汉族人稳定华法林维持剂量的总变异性。方法中山大学附属第一医院治疗的408例患者符合研究资格，且在研究开始时已获得稳定华法林维持剂量。记录人口统计学、华法林维持剂量和伴随药物。从外周血样本中提取基因组 DNA，并对 10 个 SNP（CYP2C9*2 和 *3、CYP4F2rs2108622、VKORC1−1639C>T 以及 rs10239977、rs3815455、rs41301394、rs56256515 的潜在 POR 基因）进行基因分型。结果建立了华法林维持剂量的预测模型，表明年龄、性别、体表面积、阿司匹林使用、CYP2C9*3、CYP4F2rs2108622、VKORC1−1639C>T和POR*37831–35C>T占了华法林维持剂量的预测模型。接受抗凝治疗的患者剂量差异为 42.4%。 POR*37 831–35C>T对华法林剂量变异的贡献仅为3.9%。结论SNPPOR*37831–35C>T首次被证实是与汉族华法林维持剂量个体间变异相关的次要但具有统计学意义的因素。在未来的算法中应考虑 POR*37 基因多态性，以便更快、更可靠地实现稳定的华法林维持剂量。
PurposeThe aim of this study was to investigate whether any of the single-nucleotide polymorphisms (SNPs) in thePORgene were significantly associated withCYPactivity and expression, and could contribute to the total variability in stable warfarin maintenance doses in Han Chinese.MethodsA 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 (CYP2C9*2 and *3,CYP4F2rs2108622,VKORC1−1639C>T, and potentialPORgenes of rs10239977, rs3815455, rs41301394, rs56256515, rs1057868, and rs2286823) using the Sequenom MassARRAY genotyping system.ResultsA predictive model of warfarin maintenance dose was established and indicated that age, gender, body surface area, aspirin use,CYP2C9*3,CYP4F2rs2108622,VKORC1−1639C>T, andPOR*37831–35C>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 %.ConclusionsFor the first time, the SNPPOR*37831–35C>T was confirmed as a minor but statistically significant factor associated with interindividual variation in warfarin maintenance dose in Han Chinese. ThePOR*37gene polymorphism should be considered in future algorithms for faster and more reliable achievement of stable warfarin maintenance doses.