五酯胶囊对他克莫司增效作用与CYP3A5*3基因多态性的相关性研究
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篇名: 五酯胶囊对他克莫司增效作用与CYP3A5*3基因多态性的相关性研究
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摘要: 目的:探讨五酯胶囊对他克莫司增效作用与细胞色素P450(CYP)3A5*3(rs776746,6986 A>G)基因多态性的相关性。方法:选择1997年1月-2015年12月于我院行肾移植术并于术后给予他克莫司维持治疗的患者170例,根据是否联用五酯胶囊将其分为五酯胶囊(+)组(74例)和五酯胶囊(-)组(96例)。两组患者均予他克莫司+吗替麦考酚酯+泼尼松对症治疗;五酯胶囊(+)组患者在此基础上加服五酯胶囊,每次1粒,bid。两组患者均连续治疗≥12个月。采用化学发光微粒子免疫分析技术检测患者用药后0、1、3、6、12个月后他克莫司的血药谷浓度,并计算各时间点经日剂量校正后的血药浓度(C0/D)值;采用聚合酶链反应-限制性片段长度多态性分析法检测患者CYP3A5*3基因多态性;采用协方差分析考察他克莫司C0/D值与基因多态性的相关性。结果:170例患者中,CYP3A5 GG、AG、AA基因型患者分别有65、83、22例,基因型频率分别为38.2%、48.8%和12.9%,符合Hardy-Weinberg平衡(P>0.05)。五酯胶囊(+)组GG、AG+AA基因型分布频率与五酯胶囊(-)组比较,差异有统计学意义(P<0.05)。用药1个月时,五酯胶囊(+)组GG基因型患者他克莫司C0/D值显著高于五酯胶囊(-)组同基因型患者;用药1、3、6、12个月时,五酯胶囊(+)组AG+AA基因型患者他克莫司C0/D值显著高于五酯胶囊(-)组同基因型患者,差异均有统计学意义(P<0.05)。而用药3、6、12个月时,两组GG基因型患者他克莫司C0/D值比较,差异均无统计学意义(P>0.05)。结论:五酯胶囊能提高CYP3A5*3 AG+AA基因型患者他克莫司的C0/D值,而对GG基因型患者C0/D值的影响不明显;当患者使用五酯胶囊作为他克莫司增效剂时,应考虑其CYP3A5*3基因分型。
ABSTRACT: OBJECTIVE: To investigate the association of synergistic effects of Wuzhi capsules on tacrolimus with CYP3A5*3 (6986A>G,rs776746) gene polymorphisms. METHODS: One hundred and severty patients underwent renal transplantation receiving tacrolimus maintenance therapy after surgery were selected from our hospital during Jan. 1997-Dec. 2015, and then divided into Wuzhi capsules (+)group (74 cases) and Wuzhi capsules(-)group (96 cases) according to the use of Wuzhi capsules. Both groups received tacrolimus+mycophenolate mofetil+prednisone; Wuzhi capsules (+)group was additionally given Wuzhi capsules, one capsule each time, bid, for more than 12 months. Trough concentration of tacrolimus was detected by CMIA 0, 1, 3, 6, 12 months after medication, and the blood concentrations (C0/D) were calculated at different time points after correcting daily dose. CYP3A5*3 gene polymorphisms was detected by PCR-RFLP. The association of C0/D value with gene polymorphism was investigated by analysis of covariance. RESULTS: Among 170 patients, there were 65 cases of CYP3A5 GG genotype, 83 cases of AG genotype and 22 cases of AA genotype; genotype frequencies were 38.2%, 48.8% and 12.9%, which was in line with Hardy-Weinberg balance (P>0.05). There was statistical significance in the distribution frequencies of GG, AG+AA genotype between Wuzhi capsules (+) group and Wuzhi capsules(-)group (P<0.05). After 1 month of medication, C0/D of tacrolimus in GG genotype was significantly higher in Wuzhi capsules (+)group than in Wuzhi capsules(-)group. After 1, 3, 6, 12 months of medication, C0/D of tacrolimus in AG+AA genotype was significantly higher in Wuzhi capsules (+) group than in Wuzhi capsules(-) group, with statistical significance (P<0.05). There was no statistical significance in C0/D of tacrolimus in GG genotype between 2 groups after 3, 6, 12 months of treatment (P>0.05). CONCLUSIONS: Wuzhi capsules can increase C0/D of tacrolimus in CYP3A5*3 AG+AA genotype, but have no significant effect on C0/D of tacrolimus in GG genotype; CYP3A5*3 genotype should be considered when using Wuzhi capsules as synergist of tacrolimus.
期刊: 2017年第28卷第5期
作者: 杨燕,辛华雯,刘飞,熊磊,李维亮,余爱荣
AUTHORS: YANG Yan,XIN Huawen,LIU Fei,XIONG Lei,LI Weiliang,YU Airong
关键字: CYP3A5*3;基因多态性;五酯胶囊;他克莫司;增效作用
KEYWORDS: CYP3A5*3; Gene polymorphism; Wuzhi capsules; Tacrolimus; Synergistic effects
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