CYP2C9及VKORC1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：2018-08-09 17:51

【摘要】：目的研究湖北地区汉族人性别、年龄、身高、体重、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及计算机模型预测剂量的相关性。方法收集湖北地区汉族人群临床使用华法林的患者,采用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)技术检测CYP2C9和VKORC1基因型,同时记录患者的年龄、性别、体重、身高、国际标准化比值(INR)、华法林稳态剂量和计算机模型预测剂量等临床资料,并对这些临床资料进行相关分析及多元回归分析。结果 435例患者的CYP2C9基因型检测显示402例为*1/*1型(92.41%)、30例为*1/*3型(6.90%)、3例*3/*3型(0.69%)。前两型患者华法林剂量分别为(2.91±1.12)mg/d、(1.91±0.85)mg/d,*1/*3型较*1/*1型华法林需求量少,差异有统计学意义(P0.01)(CYP2C9基因型*3/*3型样本量太少,未参与组间比较);VKORC1基因型检测显示354例为AA型(81.4%)、77例为杂合子GA型(17.7%)、4例为纯合子GG型(0.9%)。患者华法林剂量分别为(2.58±0.94)mg/d、(3.82±1.52)mg/d、(5.62±1.77)mg/d,AA型较GA型华法林需求量少,两组间比较差异有统计学意义(P0.01)(VKORC1基因型GG型样本量太少,未参与组间比较)。同时对患者的年龄、身高、体重、两种基因型、稳态剂量以及计算机模型预测剂量均分别行相关分析及多元回归分析,提示华法林剂量与患者的年龄、身高、体重及不同的基因型均有关,且相关分析提示计算机模型预测剂量与稳态剂量的相关系数为0.611,且有统计学意义;行稳态剂量的多元回归分析显示CYP2C9、VKORC1基因型、年龄、体重与稳态剂量相关,有统计学意义。结论在湖北地区汉族人群中,存在CYP2C9和VKORC1基因多态性,且不同基因型患者间华法林用量存在差异,同时华法林剂量与年龄、体重及不同的基因型有关,计算机模型预测剂量与稳态剂量存在相关性且有统计学意义。
[Abstract]:Objective to study the gender, age, height, weight of Han nationality in Hubei province. Correlation of cytochrome P450 enzyme 2C9 gene (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genotype with warfarin steady-state dose and predicted dose by computer model. Methods CYP2C9 and VKORC1 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients with warfarin. Age, sex, weight, height were recorded. International standardized ratio (INR), warfarin steady-state dose and computer model predicted dose and other clinical data, and these clinical data were analyzed and multivariate regression analysis. Results the CYP2C9 genotypes of 435 patients showed that 402 cases were 1 / 1 type (92.41%) and 30 cases were 1 / 1 / 3 (6.90%) / 3 / 3 (0.69%). The doses of warfarin in the first two types of patients were (2.91 卤1.12) mg / d, (1.91 卤0.85) mg / d and (1.91 卤0.85) mg / d / 3, respectively. The demand for warfarin in the first two types of patients was significantly lower than that in the first type of warfarin (P0.01) (P0.01). VKORC1 genotypes were detected in 354 cases of AA (81.4%) and 77 cases of heterozygote GA (17.7%). 4 cases were homozygous GG (0.9%). The doses of warfarin were (2.58 卤0.94) mg / d, (3.82 卤1.52) mg / d, (5.62 卤1.77) mg / d and (5.62 卤1.77) mg / d, respectively. The difference between the two groups was statistically significant (P0.01). Age, height, weight, two genotypes, steady-state dose and predicted dose of computer model were analyzed by correlation analysis and multivariate regression analysis, which suggested that warfarin dose was associated with age and height. The correlation coefficient between predicted dose and steady-state dose by computer model was 0.611, and the multivariate regression analysis of steady-state dose showed that CYP2C9 VKORC1 genotype, age, and age were correlated with body weight and genotype. Body weight was significantly correlated with steady dose. Conclusion there are polymorphisms of CYP2C9 and VKORC1 genes in the Han population in Hubei, and the dosage of warfarin is different among different genotypes, and the dosage of warfarin is related to age, body weight and different genotypes. There is a correlation between the predicted dose and the steady-state dose by computer model and there is statistical significance.
【作者单位】：武汉亚洲心脏病医院心外科;
【基金】：武汉市卫计委临床医学科研项目(No.WX13B28)
【分类号】：R969

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