【摘要】 目的:研究华法林剂量估算公式预测剂量与稳态剂量的一致性,以及性别、年龄、身高、体质量、体质指数(BMI)、CCR、肝功能、细胞色素P450酶2C9基因(CYP2C9)和维生素K环氧化物还原酶复合体亚单位1(VKORC1)基因型与华法林稳态剂量相关性。方法:收集在我院进行基因检测患者临床资料,采用原位杂交荧光染色脱氧核糖核酸(DNA)测序技术检测CYP2C9和VKORC1基因型,同时记录患者性别、年龄、身高、体质量、国际标准化比值(INR)、华法林日剂量、血肌酐、肝功能、模型预测剂量等临床资料,并用SPSS 21.0软件对这些资料进行相关分析和多元回归分析。结果:147例患者入选,CYP2C9(1075A>C)位点检测到*1/*1型137例(93.2%),*1/*3型9例(6.1%),*3/*3型1例(0.7),VKORC1(1639G>A)位点检测到AA型118例(80.3%),AG型27例(18.4%),GG型2例(1.4%)。55例患者出院时达稳态,其中CYP2C9(1075A>C)位点*1/*1型51例(92.7%),*1/*3型4例(7.3%),*3/*3型0例(0%),VKORC1(1639G>A)位点AA型48例(87.3%),GA型7例(12.7%),GG型0例(0%)。55例达稳态剂量患者中,估算日剂量最小值为1.4 mg,最大剂量为7 mg,平均日剂量为(2.60±0.87) mg,达稳态日剂量最小值为1 mg,最大值为6 mg,平均日剂量为(2.54±0.94) mg。达稳态患者的估算日平均剂量与达稳态日平均剂量差异无统计学意义(P>0.05)。稳态剂量与年龄、身高、体质量、肾功能、P450 CYP2C9、VKORC1有一定的相关性,且估算剂量与稳态剂量的相关系数为0.732,差异有统计学意义(P<0.05)。多元线性回归分析结果显示CYP2C9、VKORC1、年龄、身高、体质量、BMI与华法林稳态剂量有相关性(P<0.05)。结论:模型预测剂量与稳态剂量具有一致性,同时华法林稳态剂量与年龄、体质量、身高、BMI、基因型等相关。更多还原

【Abstract】 Objective: To evaluate the consistency between the IWPC predicted dose and the actual dose,and the association of gender,age,height,body weight,BMI,CCR,liver function,cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) genotypes with warfarin stable dose. Methods: The clinical data including gender,age,height,body weight,international normalized ratio (INR),daily dose of warfarin,serum creatinine,liver function and model-predicted dose of patients treated with warfarin and undergoing gene detection were collected,recorded and analyzed by correlation analysis and multivariate regression analysis with SPSS 21.0 software. CYP2C9 and VKORC1 genotypes were determined by situ hybridization fluorescence staining deoxyribonucleic acid (DNA) sequencing technology. Results: A total of 147 patients were included. CYP2C9 genotyping showed that there were 137 cases (93.2%) of * 1/* 1 type,9 (6.1%) of * 1/* 3 type and 1 (0.7%) of * 3/* 3 type,VKORC1 genotyping showed that the frequency of AA,GA and GG was 80.3% (118/147),18.4% (27/147) and 1.4% (2/147),respectively. Among the55 patients reached steady-state when discharged from hospital,the frequency of * 1/* 1,* 1/* 3 and * 3/* 3 of CYP2C9 ws92.7% (51/55),7.3% (4/55) and 0% (0/55),and 87.3% (48/55),12.7% (7/55) and 0% (0/55) of AA,GA and GG of VKORC1,resepctively. The minimum predictive daily dose of the 55 cases was 1.4 mg,the maximum predictive daily dose was 7 mg,and the average daily dose was (2.60±0.87) mg. The minimum daily dose of steady-state was 1 mg,the maximum value was 6 mg,and the average daily dose was (2.54+0.94) mg. The matched t-test was used to evaluate the consistency of the average daily dose and the average daily dose of steady-state patients. The results showed that there was no statistical difference (P>0.05). The correlation analysis and multivariate regression analysis showed that age,height,body weight,renal function,CYP2C9 and VKORC1 genotypes were related to warfarin steady-state dose,and the correlation coefficient of warfarin stable dose and the predicted dose was 0.732,and there was statistically significant difference (P< 0.05). The multivariate regression analysis showed that there was statistical association between the warfarin stable dose and age,body weight,height,BMI,CYP2C9 genotype and VKORC1 genotype (P < 0.05). Conclusion: There is consistency between daily steady-state dose and daily predicted dose. Meanwhile,the steady-state dose of warfarin is related to age,body weight,height,BMI and genotype.更多还原