Chiu King-Wah, Nakano Toshiaki, Chen Kuang-Den, Hsu Li-Wen, Lai Chia-Yun, Huang Ching-Yin, Cheng Yu-Fan, Goto Shigeru, Chen Chao-Long
Liver transplantation program, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung, 833, Taiwan.
J Biomed Sci. 2015 May 15;22(1):32. doi: 10.1186/s12929-015-0140-4.
Cytochrome P450 metabolizes many drugs in the liver. Three genotypes of CYP2C19 with extensive, intermediate, and poor metabolizing activity, respectively, have been identified in peripheral blood of transplant recipients and new liver grafts in living donor liver transplantation (LDLT). The expression of the final genotype in liver graft biopsies depends on the donor, whereas the expression in peripheral blood mononuclear cells depends on the recipient. The metabolizing isoenzyme of the major anti-rejection agents passes through CYP3A4, CYP3A5 and MDR1, which have also been identified to have similar biological characteristics as genotype of CYP2C19 in liver tissue. Recently, pyrosequencing has been used to investigate the expressions of different genotypes in liver grafts in LDLT. This review focuses on recent findings regarding the biological expressions of the CYP2C19, CYP3A4, CYP3A5 and MRD1 genotypes in liver grafts before and after LDLT. The application of pyrosequencing may be beneficial in further research on liver transplantation. Laser capture microdissection of hepatocytes in liver grafts may be a direction for future research.
细胞色素P450在肝脏中代谢多种药物。在活体肝移植（LDLT）受者的外周血和新肝移植物中，已分别鉴定出具有广泛、中等和低代谢活性的三种CYP2C19基因型。肝移植活检中最终基因型的表达取决于供体，而外周血单个核细胞中的表达取决于受者。主要抗排斥药物的代谢同工酶通过CYP3A4、CYP3A5和MDR1，它们在肝组织中的生物学特性也与CYP2C19基因型相似。最近，焦磷酸测序已用于研究LDLT中肝移植物中不同基因型的表达。本综述重点关注LDLT前后肝移植物中CYP2C19、CYP3A4、CYP3A5和MRD1基因型生物学表达的最新研究结果。焦磷酸测序的应用可能有助于肝移植的进一步研究。肝移植物中肝细胞的激光捕获显微切割可能是未来研究的一个方向。
