Anand Aishwarya, Kumar Rupesh, Sharma Swati, Gupta Ankur, Vijayvergiya Rajesh, Mehrotra Saurabh, Kumar Basant, Lad Deepesh, Patil Amol N, Shafiq Nusrat, Malhotra Samir
Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Department of Cardiothoracic and Vascular Surgery, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Drug Metab Pers Ther. 2023 Apr 19;38(3):273-279. doi: 10.1515/dmpt-2022-0189. eCollection 2023 Sep 1.
A study was conducted to develop and validate the warfarin pharmacogenetic dose optimization algorithm considering the clinical pharmacogenetic implementation consortium (CPIC) recommendations for the Asian ethnicity population.
The present prospective observational study recruited warfarin-receiving patients. We collected a three ml blood sample for VKORC1, CYP2C92, CYP2C93, and CYP4F2 polymorphism assessment during the follow-up visits. Clinical history, sociodemographic and warfarin dose details were noted.
The study recruited 300 patients (250 in derivation and 50 in validation timed cohort) receiving warfarin therapy. The baseline characteristics were similar in both cohorts. BMI, presence of comorbidity, VKORC1, CYP2C92, and CYP2C93 were identified as covariates significantly affecting the warfarin weekly maintenance dose (p<0.001 for all) and the same were included in warfarin pharmacogenetic dose optimization algorithm building. The algorithm built-in the present study showed a good correlation with Gage (r=0.57, p<0.0001), and IWPC (r=0.51, p<0.0001) algorithms, widely accepted in western side of the globe. The receiver operating characteristic curve analysis showed a sensitivity of 73 %, a positive predictive value of 96 %, and a specificity of 89 %. The algorithm correctly identified the validation cohort's warfarin-sensitive, intermediate reacting, and resistant patient populations.
Validation and comparisons of the warfarin pharmacogenetic dose optimization algorithm have made it ready for the clinical trial assessment.
开展一项研究，以制定并验证考虑临床药物基因组学实施联盟（CPIC）针对亚洲族裔人群建议的华法林药物基因组学剂量优化算法。
本前瞻性观察性研究招募了接受华法林治疗的患者。在随访期间，我们采集了3毫升血样用于评估VKORC1、CYP2C92、CYP2C93和CYP4F2基因多态性。记录临床病史、社会人口统计学和华法林剂量细节。
该研究招募了300名接受华法林治疗的患者（250名用于推导，50名用于验证定时队列）。两个队列的基线特征相似。BMI、合并症的存在、VKORC1、CYP2C92和CYP2C93被确定为显著影响华法林每周维持剂量的协变量（所有p<0.001），并被纳入华法林药物基因组学剂量优化算法构建中。本研究构建的算法与全球西方广泛接受的Gage算法（r=0.57，p<0.0001）和IWPC算法（r=0.51，p<0.0001）显示出良好的相关性。受试者工作特征曲线分析显示敏感性为73%，阳性预测值为96%，特异性为89%。该算法正确识别了验证队列中的华法林敏感、中等反应和耐药患者群体。
华法林药物基因组学剂量优化算法的验证和比较使其已准备好进行临床试验评估。
