Subiabre Valeska, Palomo Ivan, Guzmán Neftalí, Retamales Eduardo, Henríquez Hugo, Gonzalez Luis
The Clinical and Immunohematological Department, Faculty of Health Sciences, Universidad de Talca, Talca, Chile ; Molecular Diagnosis Laboratory, Faculty of Health Sciences, Universidad San Sebastián, Concepcion, Chile.
The Clinical and Immunohematological Department, Faculty of Health Sciences, Universidad de Talca, Talca, Chile.
Curr Ther Res Clin Exp. 2015 Jan 8;77:31-4. doi: 10.1016/j.curtheres.2014.12.002. eCollection 2015 Dec.
Vitamin K antagonists are drugs that are widely prescribed around the world and their use has helped improve the prognosis of patients with thromboembolic disease. However, a high interindividual variability has been observed in dosage requirements to reach the desired anticoagulation range that could be due to environmental and genetic factors. Studies suggest that ethnicity influences coumarin response, supporting the observed differences in dose requirements across various populations. Studies using mitochondrial DNA (mtDNA) markers have suggested that the Chilean population has a predominantly Amerindian genetic pool.
To evaluate the influence of ethnicity, defined by the presence of Amerindian mtDNA haplogroups, on the variability in therapeutic response to warfarin in the Chilean population.
A total of 191 patients treated with warfarin were included in this study. Analysis of the mitochondrial genome for detecting the presence of Amerindian mtDNA haplogroups was performed using polymerase chain reaction and polymerase chain reaction restriction fragment length polymorphism techniques. The evaluation of warfarin requirements according to each haplogroup was performed by ANOVA with a 95% CI and assuming statistical significance at P < 0.05.
Based on the presence of an mtDNA haplogroup, 91% of the Chilean population had an Amerindian background. There were no significant differences in warfarin dosage requirements among the different Amerindian haplogroups (P = 0.083).
The presence of Amerindian mtDNA haplogroup does not influence warfarin dosage requirements in the Chilean population.
维生素K拮抗剂是在全球广泛应用的药物,其使用有助于改善血栓栓塞性疾病患者的预后。然而,在达到所需抗凝范围的剂量需求方面观察到个体间存在很大差异,这可能是由环境和遗传因素导致的。研究表明种族会影响香豆素反应,这支持了不同人群在剂量需求上存在差异的观察结果。使用线粒体DNA(mtDNA)标记的研究表明,智利人群主要具有美洲印第安人的基因库。
评估由美洲印第安人mtDNA单倍群的存在所定义的种族对智利人群对华法林治疗反应变异性的影响。
本研究共纳入191例接受华法林治疗的患者。使用聚合酶链反应和聚合酶链反应限制性片段长度多态性技术对线粒体基因组进行分析,以检测美洲印第安人mtDNA单倍群的存在。根据每个单倍群对华法林需求进行评估,采用方差分析,95%置信区间,P<0.05时具有统计学意义。
基于mtDNA单倍群的存在,91%的智利人群具有美洲印第安人背景。不同美洲印第安人单倍群之间的华法林剂量需求无显著差异(P = 0.083)。
美洲印第安人mtDNA单倍群的存在不影响智利人群对华法林的剂量需求。