基于临床参考及基因因素建立华法林稳定维持剂量预测模型

Establishment of A Prediction Model for The Stable Maintenance Dose of Warfarin Based on the Clinical Reference and Genetic Factors

关键词:  华法林  基因多态性  临床参考因素  稳定维持剂量  非瓣膜病心房纤颤

Key words:  warfarin  genetic polymorphisms  clinical reference factors  stable maintenance dose  non-vavular-disease atrial fibrillation (NVAF)

摘要:

目的 探讨华法林应用的临床参考因素及基因因素与华法林稳定维持剂量的相关性，并尝试构建适用于非瓣膜病心房纤颤（non-valvular-disease atrial fibrillation，NVAF）患者华法林稳定维持剂量的预测模型。方法 按照纳入标准共纳入126例患者，应用测序反应通用试剂盒及荧光检测仪检测细胞色素P450 2C9和维生素K环氧化物还原酶基因多态性，同时记录华法林应用的临床参考因素：年龄、体质量、房颤栓塞风险评分系统（CHA₂DS₂-VASc）评分、房颤出血风险评分系统（HAS-BLED）评分、谷丙转氨酶（glutamic-pyruvic transaminase，ALT）、肾小球滤过率（glomerular filtration rate，GFR）、左心室射血分数（left ventricular ejection fraction，LVEF）、二尖瓣环水平左室侧壁组织多普勒S波；采用相关性分析探讨临床参考因素及基因多态性与华法林稳定维持剂量的相关性，并通过多元线性回归建立了华法林稳定维持剂量预测模型。结果 体质量、ALT水平、二尖瓣环水平左室侧壁组织多普勒S波与华法林稳定维持剂量成正相关，年龄、CHA₂DS₂-VASc评分、HAS-BLED评分则成负相关，而LVEF、GFR未显示明显的相关性。建立的预测模型对已有样本验证准确率达55.6%。结论 该模型可用于预测NVAF患者华法林稳定维持剂量。

Abstract:

OBJECTIVE To explore the correlation of warfarin clinical reference factors and genetic factors and warfarin stable maintenance dose, and try to construct a predictive model for the stable maintenance dose of warfarin in patients with non valvular non-valvular-disease atrial fibrillation (NVAF). METHODS The genetic polymorphisms of cytochrome P450 2C9 and vitamin K epoxide reductase were detected in 126 patients who were selected according to the inclusion criteria, using the sequencing reaction general kit and fluorescence detector. The clinical reference factors of warfarin were recorded at the same time:age, body mass, atrial fibrillation risk scoring system (CHA₂DS₂-VASc) score, atrial fibrillation risk score system (HAS-BLED) score, glutamic-pyruvic transaminase (ALT), glomerular filtration rate (GFR), left ventricular ejection fraction (LVEF), mitral valve ring left ventricular wall tissue doppler S. The correlation analysis was used to investigate the correlation between the clinical reference factors and the stable maintenance dose of warfarin. The warfarin stable maintenance dose prediction model was established by multiple linear regression. RESULTS The study showed that body mass, level of ALT, mitral valve ring left ventricular wall tissue doppler S were positively correlated with the stable maintenance dose of warfarin, while the age, CHA₂DS₂-VASc score, HAS-BLED score were were negatively correlated, while LVEF and GFR did not show significant correlation. The accuracy rate of the existing samples was 55.6%. CONCLUSION The model can be used to predict the stable maintenance dose of warfarin in NVAF patients.