The Effects Of CYP2D6SNP On Cyclosporine A Metabolism In Renal Transplantation Recipients

Objective:To investigate the effect of cytochrome P450(CYP)2D6polymorphism on cyclosporine A (CsA) pharmacokinetics and the feasibility of personalized CsA treatments base on the respective CYP2D6single nucleotide polymorphisms (SNP).Method:69renal transplantation recipients were studied. CYP2D6alleles were confirmed through high-resolution melting (HRM). Blood samples were collected on the28th day after renal transplantation and renal functions (serum creatinine, blood urea nitrogen and uric acid) and peak blood CsA concentration (C2) were measured. The respective CsA dosages in different genotype recipients were compared to analyze the correlation between SNP and CsA pharmacokinetics.Results:(1) CYP2D6100Cr>T allele frequency in this study was71%, combined of40.6%mutant-homozygote (TT) type and30.4%heterozygote (CT) type, while the remaining29%were wild-type (CC) genotype;(2) There is no considerable variability in the CYP2D6allele distribution in different gender or age groups (p>0.05);(3) Several criteria for renal function were compared, no difference was found among those3groups (p>0.05). All patients had reached the targeted CsA C2of900～1100ng/ml under therapeutic drug monitoring (TDM);(4) CYP2D6100C>T CC carriers required a higher dosage of CsA as compared to the CT and TT carriers (p<0.05);(5) No correlation was found between CsA dosage and CsA C2in CYP2D6100C>T CC allele carriers (p>0.05, R2=0.14).Conclusions:(1) CYP2D6100C>T allele frequency in this study was71%(40.6%TT,30.4%CT), with the remaining29%CC;(2) CYP2D6100C>T polymorphism is correlated with CsA dosage, CC carriers required higher a dosage of CsA;(3) CYP2D6100C>T polymorphism is not a complete predictor for the necessity of personalized CsA treatments; additionally;(4) HRM is practical for clinical SNP testing.