Effect of Polymorphisms in ABCB1 and CYP3A5 on Blood Concentrations of Cyclosporine A in Myasthenia Gravis Patients
ZHANG Ya-tong1, ZHANG Hua2,YANG Li-ping1, SHAO Hong3, LI Ke-xin1, SUN Chun-hua1
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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
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 C1236T,G2677A/T and C3435T were closely linked and the most popular haplotypes were 1236C-2677G-3435C and 1236T-2677T-3435T. The significant impact of CYP3A5*1/*3、ABCB1 C1236T and ABCB1 G2677T on blood levels were found ,and individuals with mutant genotype have higher blood levels than those with mide genotype. Moreover, in the form of haplotype, the trend of TT-TT-TT> CT-GT-CT > CC-GG-CC in blood levels was also observed. CONCLUSION There are some meaningfulness to rationalize the medication of cyclosporine A through the investigations of pharmacogenomics.
ZHNG Y-tong;ZHNG Hu;YNG Li-ping;SHO Hong;LI Ke-xin;SUN Chun-hu.
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
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