Abstract:

BACKGROUND: Calcineurin inhibitor is one of the important first-line drugs utilized in antirejection therapy following organ transplantation, which performed metabolism in CYP3A subfamily comprising CYP3A5. However, the correlation between CYP3A5 genetic polymorphism and calcineurin inhibitor-induced chronic nphrotoxicity remains poorly understood.     
OBJECTIVE: To observe the relationship between CYP3A5 genetic polymorphism calcineurin inhibitor-induced chronic nphrotoxicity in Chinese population.
METHODS: Blood samples and clinical data were collected from 200 Chinese patients with calcineurin inhibitor drug-induced chronic nephrotoxicity and 200 Chinese kidney allograft recipients without chronic nephrotoxicity as the controls. DNA was extracted from the blood samples, and the frequencies of CYP3A5 genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the polymorphisms of CYP3A5 and the calcineurin inhibitor drug-induced chronic nephrotoxicity was analyzed.
RESULTS AND CONCLUSION: The frequencies of the 3 gene types CYP3A5 *1/*1, *1/*3, and *3/*3 were 51% (102/200), 34.5% (69/200) and 14.5% (29/200) respectively in patients with calcineurin inhibitor drug-induced chronic nephrotoxicity, and 49.5% (99/200), 45% (90/200), and 5.5% (11/200), respectively in the control group. A statistical difference was found between the cases and the controls (χ² = 9.000, P < 0.05, OR = 1.638, 95%CI = 1.078 – 2.488). Logistic regression analysis showed that the polymorphism of CYP3A5*1/*1 and CYP3A5*1/*3 remained a significant independent risk factor for calcineurin inhibitor drug-induced chronic nephrotoxicity after kidney allograft. Polymorphisms of CYP3A5 were found to be significantly associated with the risk of calcineurin inhibitor drug-induced chronic nephrotoxicity, possibly as a result of higher concentrations of toxic metabolites.