Effect of Polymorphisms in MDR1 and CYP3A5 on Blood Concentrations of Cyclosporine A in Aplastic Anemia Patients

OBJECTIVE To determine the relationship between the Polymorphisms in MDR1 and CYP3A5 and the Blood Concentrations of Cyclosporine A in aplastic anemia patients. METHODS 73 aplastic anemia patients (AA) were genotyped on MDR1 G2677T/A using Gene sequencing method and MDR1C1236T, MDR1 C3435T, CYP3A5*3 using 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 There were only two types of gene *1*3 and *3*3 found in this paper. The C_0t in *3*3 of group was higher than that in *1*3 group(P<0.05). There was no significant difference between the various genotypes of MDR1 C1236T and MDR1 C3435T in C_0t. The C_0t in C2677T/A(TT/TA) was (40±23.85)μg·kg·mL^-1·mg^-1 which was higher than the wild type(GG). Linkage analysis showed that 1236TT-2677TT/A-3435TT, 1236CT-2677GT/A-3435CT and 1236CC-2677GG-3435CC were closely linked. Moreover, in the form of haplotype, the trend of TT-TT/A-TT>CT-GT/A-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.