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| ABCB1和CYP3A5基因多态性对环孢素血药浓度的影响 | |
| 引用本文： | 张亚同,张华,杨莉萍,邵宏,李可欣,孙春华. ABCB1和CYP3A5基因多态性对环孢素血药浓度的影响[J]. 中国药学杂志, 2011, 46(5): 368-373 |
| 作者姓名： | 张亚同 张华 杨莉萍 邵宏 李可欣 孙春华 |
| 作者单位： | 卫生部北京医院药学部;卫生部北京医院神经内科;北京大学药学院药事管理与临床药学系; |
| 摘 要： | 目的 研究ABCB1基因和CYP3A5基因多态性与重症肌无力患者环孢素药物浓度的关系。方法 在129名重症肌无力(MG患者中，采用荧光PCR法测定ABCB1 C3435T基因型；RFLP法分析ABCB1 C1236T， ABCB1 G2677A/T；Mismatch RFLP(错配PCR+RFLP法分析CYP3A5*3基因型，并对这4个位点进行连锁分析。收集患者临床资料，对患者环孢素血药浓度进行检测，并对患者遗传学数据和血药浓度等进行分析。结果 连锁分析显示4个SNP中，ABCB1 C1236T，G2677A/T和C3435T之间紧密连锁，ABCB1中最常见的两个单倍体型分别是1236C-2677G-3435C和1236T-2677T-3435T。另外发现CYP3A5*1/*3位点、ABCB1 C1236T位点和ABCB1 G2677T位点的多态性变化对环孢素血药浓度有明显影响，突变型组的血药浓度明显比野生型组高。同时根据ABCB1单倍体型分组，各组之间药物浓度比较都是TT-TT-TT> CT-GT-CT > CC-GG-CC。结论 药物基因学研究对环孢素治疗重症肌无力患者的临床合理用药有指导意义。 |
| 关 键 词： | ABCB1 CYP3A5 重症肌无力 环孢素 药物遗传学 |
| 收稿时间： | 2011-11-11; |
Effect of Polymorphisms in ABCB1 and CYP3A5 on Blood Concentrations of Cyclosporine A in Myasthenia Gravis Patients |
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| ZHANG Ya-tong,ZHANG Hua,YANG Li-ping,SHAO Hong,LI Ke-xin,SUN Chun-hua. Effect of Polymorphisms in ABCB1 and CYP3A5 on Blood Concentrations of Cyclosporine A in Myasthenia Gravis Patients[J]. Chinese Pharmaceutical Journal, 2011, 46(5): 368-373 | |
| Authors: | ZHANG Ya-tong ZHANG Hua YANG Li-ping SHAO Hong LI Ke-xin SUN Chun-hua |
| Affiliation: | ZHANG Ya-tong1,ZHANG Hua2,YANG Li-ping1,SHAO Hong3,LI Ke-xin1,SUN Chun-hua1(a.Department of Pharmacy,b.Neurology Department,1.Beijing Hospital,Ministry of Health,Beijing 100730,China,2.Department of Pharmacy Administration & Clinical Pharmacy,School of Pharmaceutical Science,Peking University,Beijing 100083,China) |
| Abstract: | OBJECTIVE To determine whether ABCB1 C3435T effect the pharmacokinetics of cyclosporine A in myasthenia gravispatients.METHODS 129 Myasthenia gravis patients were genotyped on ABCB1 C3435T using real-time PCR method,ABCB1 C1236T,ABCB1 G2677A/T using RFLP methods and CYP3A5*3 using Mismatch RFLP methods.The four SNPs were treated with linkage analysis.Clinical data and cyclosporine concentrations were collected and analyzed in relationship with genotyping results.RESULTS Linkage analysis showed that ABCB1 C1... |
| Keywords: | ABCB1 CYP3A5 myasthenia gravis cyclosporine A pharmacogenomics blood concentrations |
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