CYP3A5基因多态性对重症肌无力患者他克莫司血药浓度的影响  

Effect of CYP3A5 genetic polymorphism on tacrolimus concentration in myasthenia gravis patients

作　　者：陈頔[1] 侯世芳[2] 赵明[1] 孙雪林[1] 张华[2] 杨莉萍[1] 

机构地区：[1]北京医院国家老年医学中心药学部药物临床风险与个体化应用评价北京市重点实验室,北京100730 [2]北京医院国家老年医学中心神经内科,北京100730

出　　处：《中华神经医学杂志》2018年第1期48-52,共5页Chinese Journal of Neuromedicine

摘　　要：目的观察CYP3A5基因多态性对重症肌无力患者他克莫司血药浓度的影响，探讨不同基因型患者的适宜剂量。方法选择自2013年1月至2015年12月北京医院神经内科收治的重症肌无力患者95例为研究对象，采用荧光染色原位杂交检测方法检测CYP3A5基因位点、化学发光微粒子免疫分析法测定他克莫司的全血谷浓度，比较不同基因型患者之间他克莫司血药浓度测定结果、用药剂量及浓度／剂量比值（C／D）。结果95例患者中CY丹A5基因型为CYP3A5＊1＊1者14例（14．74％）、CYP3A50103者35例06．84％）、CYP3A5＊3＊3者46例似8．42％）。＊1和＊3的等位基因频率分别为33．16％和66．84％。3组患者C／D值差异有统计学意义（F=24．860，P=0．000），其中CYP3A5＊1＊1组的C／D值低于明显CYP3A5＊1＊3组，CYP3A5＊1＊3组明显低于CYP3A5＊3＊3组，差异均具有统计学意义愀0．05）。在41例次血药浓度达标的患者中，CYP3A5＊1＊1者仅有2例，剂量分别为4mg／d和5mg／d；CYP3A5＊1＊3者10例，其中9例（90％）剂量为2—3mg／d；CYP3A5＊3＊3者29例，其中28例（96．55％）的剂量为2—3mg／d。结论CY丹A5基因多态性可影响重症肌无力患者他克莫司的血药浓度，该基因检测有助于患者个体化用药的剂量选择。Objective To investigate the effect of CYP3A5 genetic polymorphism on tacrolimus concentration in myasthenia gravis patients to explore the optimum doses for patients of different genotypes. Methods The CYP3A5 genotypes of 95 myasthenia gravis patients treated with tacrolimus in our hospital from January 2013 to December 2015, were determined by fluorescence in situ hybridization and tacrolimus concentrations were determined by chemiluminescence microparticle immuno assay. The differences of tacrolimus concentrations/dosage （C/D） ratios, concentration and dosage of tacrolimus were compared among patients of different genotypes. Results There were 14 patients （14.74%） with CYP3A5＊1＊1, 35 （36.84%） with CYP3A5＊1＊3 and46 （48.42%） with CYP3A5＊3＊3 in these 95 patients. The allele frequencies of ＊1 and ＊3 were 33.16% and 66.84%, respectively. The C/D ratios of patients from the 3 groups were significantly different （F=24.860, P=0.000）： the C/D ratio of CYP3A5＊1/＊1 patients was significantly lower than that of CYP3A5＊1/＊3 patients （P〈0.05）, and that of CYP3A5＊1＊3 carders was significantly lower than that of CYP3A5＊3/＊3 patients （P〈0.05）. The appropriate doses of tacrolimus of myasthenia gravis patients were different in different genotypes patients： the dose of patients with CYP3A5＊ 1 ＊ 1 was 4-5 mg/d, that of CYP3A5＊3＊3 was 2-3 mg/d, and that of CYP3A5＊1＊3 was between that of CYP3A5＊1＊1 and CYP3A5＊3＊3.Conclusions The polymorphism of CYP3A 5 genetic polymorphism has effect on plasma concentrations of tacrolimus in patients with myasthenia gravis. Clinical application of pharmacogenetic studies will be helpful for individualization of tacrolimus appropriate dosage.

关 键 词：重症肌无力 他克莫司 CYP3A5 基因多态性 血药浓度 

分 类 号：R746[医药卫生—神经病学与精神病学]