Association between genetic polymorphism of CYP3A5 and blood con-centration/dose ratio of cyclosporine combined with calcium channel blockers in renal transplant patients

Abstract

Abstract: AIM: To study the relationship be-tween the genetic polymorphism of CYP3A5 gene and the blood concentration/dose ( C/D) ratio of cyclospo-rine combined with calcium channel blockers ( CCBs) in renal transplant patients.METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was applied to determine the genotype of CYP3A5 in 69 renal transplant patients. The blood concentration/dose (C/D) ratio of cyclospo-rine was compared in patients coadministrated of CCBs with different genetic polymorphism of CYP3A5.RE-SULTS: The cases of genotype of CYP3A5 ＊1/＊1, CYP3A5＊1/＊3 and CYP3A5 ＊3/＊3 were 8,23 and 38, respectively .The mutation rate of CYP3A5＊ 3 in renal transplant patients was 71.74%.The CsA C/D ratio of patients of CYP3A5＊1/＊1 and CYP3A5 ＊1/＊3were 1 .73 and 2.43 times higher than that in patients of CYP3A5 ＊3/＊3.The CsA C/D ratio of patients ( CYP3A5 ＊1/＊1, CYP3A5 ＊1/＊3) com-binedwith CCBs had been obviously elevated ( 19.90 ±7.66 vs 36.01±8.18, 34.33 ±7.87 vs 46.16± 9.63 ng·mL^-1 per mg·kg^-1 ;P <0.01, P <0.05) , and that of patients with CYP3A5 ＊3/＊3 genotype showed no significant changes ( 48.27 ±10 .60 vs 46.42 ±9.24 ng·mL^-1 per mg·kg^-1 ).CONCLUSION: The CsA C/D ratio is related to the genetic polymorphism of CYP3A5 gene in renal transplant pa-tients combined with CCBs.

Key words: kidney transplantation, cyclosporine, calcium channel blockers, CYP3A5, genetic polymor-phisms

CLC Number:

R969

SHI Dao-hua, LIN Zhi-jie. Association between genetic polymorphism of CYP3A5 and blood con-centration/dose ratio of cyclosporine combined with calcium channel blockers in renal transplant patients[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(10): 1149-1153.

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