瓣膜置换术后华法林稳定剂量预测模型研究

Study on prediction model of stable dosage of warfarin after valve replacement

目的:研究瓣膜置换术后CYP2C9~*2、CYP2C9~*3、CYP4F2、GGCX、VKORC1-1173、VKORC1-1639基因多态性及人口学、临床因素对瓣膜置换术后华法林稳定剂量的影响,建立华法林稳定剂量的预测模型。方法:收集226例瓣膜置换患者,提取DNA,设计引物,应用聚合酶链式反应(PCR)技术扩增上述位点基因,应用酶切技术,以特定内切酶切出相关基因,以电泳显示最终结果,得出目标DNA基因序列,回顾追踪患者服药剂量、临床资料、人口学特征,并长期监测其国际标准化比值(INR),结合有无出血、血栓形成,得出瓣膜置换术后华法林稳定剂量预测模型。结果:得出华法林稳定剂量预测模型:Y=2.131-1.816VKORC1-1173+0.369GGCX+1.529BSA-0.013Age(V1173当基因型为AA型时,取1,非AA型取0,当GGCX为GT型时取1,非GT型取0,BSA单位为m^2,Age单位为岁)。华法林稳定剂量与体表面积、年龄、VKORC1-1173、GGCX基因型相关,与CYP2C9~*2、CYP2C9~*3、CYP4F2、VKORC1-1639无明显线性关系。结论:VKORC1-1173的AA基因型与年龄及华法林稳定剂量呈负相关,而GGCX的GT基因型与体表面积及华法林稳定剂量呈正相关。

Objective： To study the effects of CYP2C9-＊2, CYP2C9-＊3, CYP4F2, GGCX, VKORC1-1173, VKORC1-1639 gene polymorphisms and the effects of demographic and clinical factors on the stable dose of warfarin after valve replacement, and to establish a prediction model of stable dose of warfarin. Methods： 226 patients with valve replacement were enrolled in this study. Extract DNA, Primers were designed and amplified by polymerase chain reaction（PCR） and the endogenous gene was digested with specific endonuclease. The specific results were obtained by electrophoresis. The target DNA gene sequence was obtained. The patient＇s dose, clinical data and demographic characteristics and the INR were tracked. With or without presence bleeding and thrombosis, Warfarin stable dose prediction model was inferred after valve replacement. Results： The prediction model of warfarin was obtained：Y = 2.131-1.816 V1173＋ 0.369 GGCX ＋1.529 BSA-0.013 Age（VKORC1-1173 When the genotype is AA type, take 1, non-AA to take 0, when GGCX for the GT type 1, non-GT take0,BSA unit is ㎡, Age unit is year）. The stable dose of warfarin was not strongly correlated with the expression of CYP2C9 -＊2, CYP2C9 -＊3,CYP4F2 and VKORC1-1639, and was related to the body surface area, age, VKORC1-1173 and GGCX genotype. Conclusion： The AA genotype of VKORC1-1173 and age could be negatively correlated with warfarin stable dose, while GT genotype of GGCX and BSA may have a positive correlation with the stable dose of warfarin.