Al-Eitan Laith N, Elsaqa Barakat Z, Almasri Ayah Y, Aman Hatem A, Khasawneh Rame H, Alghamdi Mansour A
Department of Biotechnology and Genetic Engineering, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid 22110, Jordan.
Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.
Pharmgenomics Pers Med. 2020 Nov 17;13:619-632. doi: 10.2147/PGPM.S274246. eCollection 2020.
Cardiovascular disease is one of the most common causes of morbidity and mortality worldwide. Several cardiovascular diseases require therapy with warfarin, an anticoagulant with large interindividual variability resulting in dosing difficulties. The selected genes and their polymorphisms have been implicated in several Genome-Wide Association Study (GWAS) to be associated with cardiovascular disease.
The goal of this study is to discover if there are any associations between rs646776 of , rs660240 and rs12740374 of , and rs602633 of to coronary heart disease (CHD) and warfarin dose variability in patients diagnosed with cardiovascular disease undergoing warfarin therapy.
The study was directed at the Queen Alia Hospital Anticoagulation Clinic in Amman, Jordan. DNA was extracted and genotyped using the Mass ARRAY™ system, statistical analysis was done using SPSS.
The study found several associations between the selected SNPs with warfarin, but none with cardiovascular disease. All 4 studied SNPs were found to be correlated to warfarin sensitivity during the stabilization phase except rs602633 and with warfarin dose variability at the initiation phase. SNPs also showed association with dose variability during the stabilization phase. Also, rs646776 and rs12740374 were linked to warfarin sensitivity over the initiation phase. Only rs602633 was associated with INR treatment outcomes.
The findings presented in this study found new pharmacogenomic associations for warfarin, that warrant further research in the field of genotype-guided warfarin dosing.
心血管疾病是全球发病和死亡的最常见原因之一。几种心血管疾病需要使用华法林进行治疗，华法林作为一种抗凝剂，个体间差异较大，导致给药困难。在多项全基因组关联研究（GWAS）中，已发现某些选定基因及其多态性与心血管疾病有关。
本研究的目的是发现基因的rs646776、基因的rs660240和rs12740374以及基因的rs602633与冠心病（CHD）之间以及与接受华法林治疗的心血管疾病患者的华法林剂量变异性之间是否存在关联。
该研究针对约旦安曼的阿莉亚女王医院抗凝门诊。使用Mass ARRAY™系统提取DNA并进行基因分型，使用SPSS进行统计分析。
该研究发现选定的单核苷酸多态性（SNP）与华法林之间存在多种关联，但与心血管疾病无关。除rs602633外，在稳定期发现所有4个研究的SNP均与华法林敏感性相关，在起始期与华法林剂量变异性相关。SNP在稳定期也显示出与剂量变异性有关联。此外，rs646776和rs12740374在起始期与华法林敏感性相关。只有rs602633与国际标准化比值（INR）治疗结果相关。
本研究结果发现了华法林新的药物基因组学关联，这值得在基因型指导华法林给药领域进行进一步研究。
