背景:药物基因组学(PGx)测试已证明其对于一些常用的心血管疾病(CVD)药物的实用性和成本效益。此外,PGx指导的给药指南现在可用于多种CVD药物,包括氯吡格雷,华法林,和他汀类药物。阿拉伯联合酋长国(UAE)人口多样化和多种族,全国有150多个国籍。PGx测试不是大多数全球医疗保健环境中的护理标准的一部分,包括阿联酋的医疗系统。最近批准了第一个在CVD中进行的药物基因组学临床研究,但是在开始之前需要评估多种考虑因素。本报告评估了PGx临床实施程序以及在阿联酋实施PGx实施计划的潜在好处,并具有全球影响。
方法:患者开了一种或多种以下药物:氯吡格雷,阿托伐他汀,瑞舒伐他汀,还有华法林,被招募。通过实时PCR对与研究药物相互作用的基因处的选择的遗传变体进行基因分型。
结果:对于当前的试点研究,招募了160名患者。基因型和推断的单倍型,二倍体,预测表型显示,11.9%的参与者是不良的CYP2C19代谢者,35%的中间代谢者,28.1%正常代谢,和25%快速或超快速代谢者。值得注意的是,我们队列中46.9%的人应该得到建议,避免使用氯吡格雷或考虑替代药物。关于华法林,只有20%的参与者在VKORC1-1639G>A时表现出参考等位基因,CYP2C9*2和CYP2C9*3,在两个基因中的任一个留下80%的替代基因型,其可以整合到华法林给药算法中并且可以在患者接受华法林处方时使用。对于他汀类药物,31.5%的患者在基因分型的SLCO1B1变体(rs4149056)携带至少一个等位基因,增加他们患肌病的风险。我们队列的96%接受了至少一个PGx产生的研究药物的临床推荐。
结论:当前的试点分析验证了PGx测试的可行性,以及当前使用次优药物治疗方案的患者的不可预见的高频率,这可能会从PGx测试中受益。
BACKGROUND: Pharmacogenomic (PGx) testing has proved its utility and cost-effectiveness for some commonly prescribed cardiovascular disease (CVD) medications. In addition, PGx-guided dosing guidelines are now available for multiple CVD drugs, including clopidogrel, warfarin, and statins. The United Arab Emirates (UAE) population is diverse and multiethnic, with over 150 nationalities residing in the country. PGx-testing is not part of the standard of care in most global healthcare settings, including the UAE healthcare system. The first pharmacogenomic implementation clinical
study in CVD has been approved recently, but multiple considerations needed evaluation before commencing. The current report appraises the PGx-clinical implementation procedure and the potential benefits of pursuing PGx-implementation initiatives in the UAE with global implications.
METHODS: Patients prescribed one or more of the following drugs: clopidogrel, atorvastatin, rosuvastatin, and warfarin, were recruited. Genotyping selected genetic variants at genes interacting with the
study drugs was performed by real-time PCR.
RESULTS: For the current pilot
study, 160 patients were recruited. The genotypes and inferred haplotypes, diplotypes, and predicted phenotypes revealed that 11.9% of the participants were poor CYP2C19 metabolizers, 35% intermediate metabolizers, 28.1% normal metabolizers, and 25% rapid or ultrarapid metabolizers. Notably, 46.9% of our cohort should receive a recommendation to avoid using clopidogrel or consider an alternative medication. Regarding warfarin, only 20% of the participants exhibited reference alleles at VKORC1-1639G > A, CYP2C9*2, and CYP2C9*3, leaving 80% with alternative genotypes at any of the two genes that can be integrated into the warfarin dosing algorithms and can be used whenever the patient receives a warfarin prescription. For statins, 31.5% of patients carried at least one allele at the genotyped SLCO1B1 variant (rs4149056), increasing their risk of developing myopathy. 96% of our cohort received at least one PGx-generated clinical recommendation for the studied drugs.
CONCLUSIONS: The current pilot analysis verified the feasibility of PGx-testing and the unforeseen high frequencies of patients currently treated with suboptimal drug regimens, which may potentially benefit from PGx testing.