Abstract

Objective: The purpose of this study was to investigate the associations between CYP3A4*18B and CYP3A5*3 polymorphism and cyclosporine-related liver injuries in Chinese renal transplant recipients. Methods: We genotyped 339 renal transplant recipients treated with a triple immunosuppressive regimen including cyclosporine for CYP3A4*18B and CYP3A5*3 polymorphism using the polymerase chain reaction restriction fragment length polymorphism assay. Results: The incidence of liver injury in the study population was 36.9% (125/339). At 1 month after transplantation, the trough concentration of cyclosporine (C0) in the group with CYP3A4*1/*1(GG alleles) was significantly higher than in the group with CYP3A4*18B/*1 8B(AA alleles) (p < 0.05). At 3 months after transplantation, the C0 in the group with CYP3A4*1/*1 and group with CYP3A4*1/*18B was markedly higher than in the group with CYP3A4*18B/*18B (p < 0.05). The GG genotypes of CYP3A4*18B were more common in the liver injury group compared with the control group (p < 0.05). Univariate logistic regression analysis showed that subjects carrying the GG genotypes had a 5.136- and 2.528-fold higher risk of developing cyclosporine-related liver injury than those with the AA and GA genotypes. When adjusted for sex, the risk of the CYP3A4*18B genotypes was OR = 4.969 for GG compared to AA (p = 0.030), and OR = 2.634 for GG compared to GA (p = 0.025). However, no association was observed between CYP3A5*3 polymorphisms with cyclosporine-related liver injury. Conclusions: These results suggested that the wild type of CYP3A4*18B is a risk factor for the development of cyclosporine- related liver injuries in Chinese renal transplant recipients.

Author Details

Authors

• Hua-wen Xin¹
• Hui-ming Liu¹
• Yuan-qi Li²
• Hui Huang²
• Li Zhang²
• Ai-rong Yu¹
• Xiao-chun Wu¹

Departments

• ¹ Department of Clinical Pharmacology, Wuhan General Hospital of Guangzhou Command, and
• ² Monitoring Center for Adverse Reaction of Drugs and Medical Instruments of Hubei Province, Wuhan, China

Address

Hua-Wen Xin, MD, PhD
Department of Clinical Pharmacology
Wuhan General Hospital of Guangzhou Command
627 Wuluo Road, Wuhan, 430070, China
Email: [email protected]

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