基因多态性对华法林稳态剂量和模型预测剂量的相关性研究

发布时间：2018-04-28 22:41

本文选题：华法林 + 剂量　；参考：《中国医院药学杂志》2017年11期

【摘要】：目的:研究扬州地区汉族人群CYP2C9、VKORC1基因型、性别、年龄、身高、体质量与华法林稳态剂量及计算机模型预测剂量的相关性。方法:收集扬州地区汉族人群使用华法林的患者,采用基因测序的方法检测CYP2C9和VKORC1基因型,同时记录患者的年龄、性别、身高、体质量、国家化标准比值(INR)、胺碘酮使用情况临床资料,并对这些临床资料进行相关分析及多元回归分析。结果:CYP2C9基因型检测有102例为野生AA型(91.9%),8例为杂合子AC型(7.21%),1例为突变CC型(0.9%)。VKORC1基因型检测有96例为突变纯合子AA型(86.49%),13例为杂合子GA型(11.71%),2例为野生GG型(1.80%),所有基因型分布符合Hardy-Weinberg遗传平衡。VKORC1 AA型患者华法林剂量明显低于较AG型,CYP2C9*3 AC型明显低于AA型(P0.05)。对患者年龄、身高、体质量及不同基因型、模型预测剂量及稳态剂量进行相关性分析和多元回归分析,提示患者的年龄、体质量、CYP2C9和VKORC1基因多态性与华法林个体剂量相关,而相关性分析提示性别和身高对华法林剂量差异无统计学意义。本研究提示模型预测剂量与实际稳态剂量的相关系数为0.732,配对t检验预估剂量与稳态剂量之间无显著性差异。随访显示不良反应发生率为10.81%,均为轻微出血,所有基因型中AC/AA型患者出血发生率最高。结论:扬州地区汉族人群存在CYP2C9和VKORC1基因多态性,应用CYP2C9和VKORC1基因多态性和模型可以准确估测华法林剂量。
[Abstract]:Objective: to study the correlation of CYP2C9 VKORC1 genotype, sex, age, height, body mass with warfarin steady-state dose and predicted dose by computer model. Methods: CYP2C9 and VKORC1 genotypes were detected by gene sequencing in patients with warfarin in Yangzhou Han population. The age, sex, height, body weight of the patients were recorded at the same time. The clinical data of the use of amiodarone and INRX were analyzed by correlation analysis and multivariate regression analysis. Results 102 cases of CYP2C9 genotypes were detected as wild AA type 91.9 and 8 cases as heterozygotes AC type 7.21 and 1 case as CC type 0.9g 路VKORC1 genotypes. 96 cases were identified as mutant homozygous AA genotype 86.49C 1. 13 cases were heterozygous GA type 11.71M, 2 cases were wild GG type 1.80%, all genotypes were divided into two groups. The dose of warfarin in patients with Hardy-Weinberg genetic balance, VKORC1-AA was significantly lower than that in patients with AG type CYP2C9C3AC. The correlation analysis and multiple regression analysis of age, height, body weight and different genotypes, predicted dose and steady-state dose showed that age, body weight, CYP2C9 and VKORC1 gene polymorphisms were correlated with warfarin individual dose. The correlation analysis showed that gender and height had no significant difference in warfarin dose. This study suggests that the correlation coefficient between the predicted dose and the actual steady-state dose is 0.732, and there is no significant difference between the predicted dose and the steady-state dose by paired t-test. The incidence of adverse reactions was 10.81%, all of which were mild bleeding. The incidence of hemorrhage was the highest in AC/AA patients. Conclusion: CYP2C9 and VKORC1 gene polymorphisms exist in the Han population in Yangzhou area. The dosage of warfarin can be estimated accurately by using CYP2C9 and VKORC1 gene polymorphism and model.
【作者单位】：江苏省苏北人民医院药学部;江苏省苏北人民医院心内科;
【基金】：江苏省临床医学专项(编号:BL2013022) 扬州市科技发展指导计划课题(编号:YZCZSYJJ1403)
【分类号】：R969

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