本文關(guān)鍵詞： 華法林 基因多態(tài)性 VKORC CYPC 血藥濃度　出處：《第二軍醫(yī)大學(xué)學(xué)報(bào)》2016年05期 　論文類(lèi)型：期刊論文

【摘要】：目的探討上海地區(qū)漢族人群中細(xì)胞色素氧化酶P450 2C9(CYP2C9)、維生素K環(huán)氧化物還原酶復(fù)合體1(VKORC1)基因多態(tài)性對(duì)華法林穩(wěn)定劑量及華法林血漿濃度的影響。方法納入在體外循環(huán)下行瓣膜置換術(shù)且術(shù)后需服用華法林抗凝的患者226例,采用焦磷酸測(cè)序及UPLC/MS-MS法分別檢測(cè)其CYP2C9和VKORC1基因型及其華法林血漿總濃度及游離濃度,分別以基因型、性別、年齡進(jìn)行分組,比較不同組別患者華法林維持劑量和血漿濃度,并計(jì)算基因多態(tài)性及血藥濃度、性別、年齡對(duì)華法林穩(wěn)定劑量的貢獻(xiàn)率。結(jié)果 CYP2C9(1061A/C)基因型中,AA型患者華法林維持量高于AC型(P0.05);VKORC1(-1639G/A)基因型中,AG型患者華法林維持量高于AA型患者(P0.01);VKORC1(1173C/T)基因型中,CT型患者華法林維持量高于TT型患者(P0.01)。CYP2C9(1061A/C)不同基因型間其華法林血漿濃度差異無(wú)統(tǒng)計(jì)學(xué)意義,VKORC1(-1639G/A)不同基因型間及VKORC1(1173C/T)不同基因型間華法林血漿濃度差異有統(tǒng)計(jì)學(xué)意義(P0.01)。男性患者所需華法林維持量高于女性患者(P0.05),60歲以上患者所需華法林維持量低于60歲以下患者(P0.05)。CYP2C9(1061A/C)、VKORC1(-1639G/A)、VKORC1(1173C/T)基因多態(tài)性及華法林血藥濃度、年齡、性別分別解釋了7.2%、29.1%、30.4%、6.7%、1.6%和1.4%的華法林個(gè)體劑量差異,多因素聯(lián)合可解釋47.2%的華法林個(gè)體劑量差異。結(jié)論 CYP2C9基因多態(tài)性與華法林抗凝藥物劑量的個(gè)體間差異有關(guān);VKORC1基因多態(tài)性與華法林抗凝藥物劑量的個(gè)體間差異有關(guān),且與其血藥濃度密切相關(guān)。年齡和性別是影響華法林維持量的重要非基因因素。
[Abstract]:Objective to study the cytochrome oxidase P450 2C9 (CYP2C9) in the Han population of Shanghai. Vitamin K epoxide reductase complex 1 (VKORC1). Effect of gene polymorphism on warfarin stabilizer dosage and warfarin plasma concentration. Methods 226 patients with valvular replacement underwent cardiopulmonary bypass and received warfarin anticoagulant. The total plasma concentration and free concentration of warfarin and CYP2C9 and VKORC1 genotypes were detected by pyrosequencing and UPLC/MS-MS respectively. Age groups were used to compare the maintenance dose and plasma concentration of warfarin in different groups of patients, and to calculate the gene polymorphism, blood drug concentration and sex. Results the maintenance rate of warfarin in CYP2C9 1061A / C genotype was higher than that in AC genotype (P 0.05). The maintenance of warfarin in VKORC1-1639G / A genotype was higher than that in AA genotype. In the VKORC1 / 1173C / T genotype. The maintenance level of warfarin in CT patients was higher than that in TT patients (P 0.01). There was no significant difference in plasma concentrations of warfarin among different genotypes (CYP2C9 1061A / C). The plasma concentrations of warfarin were significantly different among different genotypes of VKORC1- 1639G / A and between different genotypes of VKORC1 and 1173C / T (P0.01). The maintenance of warfarin in male patients was higher than that in female patients (P 0.05). The maintenance of warfarin in patients over 60 years of age was lower than that in patients under 60 years of age (P0.05N. CYP2C9 1061A / C / VKORC1- 1639G / A.). The polymorphism of VKORC1 / 1173C / T gene and warfarin concentration, age and sex explained 7.2and 29.1C / T, respectively. The individual doses of warfarin in 1.6% and 1.4% were different. Multivariate association can explain the individual dose difference of warfarin in 47.2%. Conclusion the polymorphism of CYP2C9 gene is related to the individual difference of warfarin anticoagulant dosage. The polymorphism of VKORC1 gene is related to the individual difference of warfarin anticoagulant dosage, and it is closely related to the concentration of warfarin. Age and sex are the important non-gene factors that influence the maintenance of warfarin.
【作者單位】： 第二軍醫(yī)大學(xué)長(zhǎng)征醫(yī)院胸心外科;第二軍醫(yī)大學(xué)長(zhǎng)征醫(yī)院藥材科;
【基金】：上海市優(yōu)秀學(xué)科帶頭人計(jì)劃(12XD1400300) 上海市衛(wèi)生與計(jì)劃生育委員會(huì)青年項(xiàng)目(2012Y137)~~
【分類(lèi)號(hào)】：R969
【正文快照】： [Acad J Sec Mil Med Univ,2016,37(5):640-644]華法林(warfarin)是常用的口服抗凝藥,多用于人工瓣膜置換、血栓栓塞性疾病及房顫等的抗凝治療[1]。由于華法林的治療窗較窄,在臨床使用過(guò)程中不同個(gè)體間的穩(wěn)定治療劑量有著較大的差異,若劑量不足將導(dǎo)致血栓栓塞,而劑量過(guò)大則有

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