本文選題：華法林 + 劑量　； 參考：《中國醫(yī)院藥學(xué)雜志》2017年11期

【摘要】：目的:研究揚州地區(qū)漢族人群CYP2C9、VKORC1基因型、性別、年齡、身高、體質(zhì)量與華法林穩(wěn)態(tài)劑量及計算機模型預(yù)測劑量的相關(guān)性。方法:收集揚州地區(qū)漢族人群使用華法林的患者,采用基因測序的方法檢測CYP2C9和VKORC1基因型,同時記錄患者的年齡、性別、身高、體質(zhì)量、國家化標(biāo)準(zhǔn)比值(INR)、胺碘酮使用情況臨床資料,并對這些臨床資料進行相關(guān)分析及多元回歸分析。結(jié)果:CYP2C9基因型檢測有102例為野生AA型(91.9%),8例為雜合子AC型(7.21%),1例為突變CC型(0.9%)。VKORC1基因型檢測有96例為突變純合子AA型(86.49%),13例為雜合子GA型(11.71%),2例為野生GG型(1.80%),所有基因型分布符合Hardy-Weinberg遺傳平衡。VKORC1 AA型患者華法林劑量明顯低于較AG型,CYP2C9*3 AC型明顯低于AA型(P0.05)。對患者年齡、身高、體質(zhì)量及不同基因型、模型預(yù)測劑量及穩(wěn)態(tài)劑量進行相關(guān)性分析和多元回歸分析,提示患者的年齡、體質(zhì)量、CYP2C9和VKORC1基因多態(tài)性與華法林個體劑量相關(guān),而相關(guān)性分析提示性別和身高對華法林劑量差異無統(tǒng)計學(xué)意義。本研究提示模型預(yù)測劑量與實際穩(wěn)態(tài)劑量的相關(guān)系數(shù)為0.732,配對t檢驗預(yù)估劑量與穩(wěn)態(tài)劑量之間無顯著性差異。隨訪顯示不良反應(yīng)發(fā)生率為10.81%,均為輕微出血,所有基因型中AC/AA型患者出血發(fā)生率最高。結(jié)論:揚州地區(qū)漢族人群存在CYP2C9和VKORC1基因多態(tài)性,應(yīng)用CYP2C9和VKORC1基因多態(tài)性和模型可以準(zhǔn)確估測華法林劑量。
[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.
【作者單位】： 江蘇省蘇北人民醫(yī)院藥學(xué)部;江蘇省蘇北人民醫(yī)院心內(nèi)科;
【基金】：江蘇省臨床醫(yī)學(xué)專項(編號:BL2013022) 揚州市科技發(fā)展指導(dǎo)計劃課題(編號:YZCZSYJJ1403)
【分類號】：R969

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