1. CYP3A7, CYP3A4, and CYP3A5 genetic polymorphisms in recipients rather than donors influence tacrolimus concentrations in the early stages after liver transplantation.
- Author
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Dong, Yue, Xu, Qinxia, Li, Ruidong, Tao, Yifeng, Zhang, Quanbao, Li, Jianhua, Ma, Zhenyu, Shen, Conghuan, Zhong, Mingkang, Wang, Zhengxin, and Qiu, Xiaoyan
- Subjects
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CYTOCHROME P-450 CYP3A , *LIVER transplantation , *GENETIC polymorphisms , *TACROLIMUS , *INTESTINES , *BASILIXIMAB - Abstract
[Display omitted] • The influence of CYP3A polymorphisms on tacrolimus concentrations was investigated. • CYP3A polymorphisms of recipients affected tacrolimus concentrations. • CYP3A polymorphisms of donors did not influence tacrolimus concentrations. The purpose of this study was to investigate the effect of CYP3A7 , CYP3A4 , and CYP3A5 genetic polymorphisms in liver transplant recipients and donors on tacrolimus concentrations in the early stages after liver transplantation. One hundred and thirty-eight liver transplant recipients and matched donors were genotyped for CYP3A7 (rs10211 and rs2257401), CYP3A4 (rs4646437 and rs2242480), and CYP3A5 *3 (rs776746) polymorphisms. The relationships between dose-adjusted trough concentrations (C 0 /D) of tacrolimus and corresponding genotypes were investigated. Recipient CYP3A polymorphisms were associated with tacrolimus concentrations. The CYP3A7 rs10211 AA carriers (186.2 vs 90.5, p < 0.001), CYP3A4 rs4646437 CC carriers (184.0 vs 88.8, p < 0.001), CYP3A4 *1G rs2242480 CC carriers (189.8 vs 99.7, p < 0.001), and CYP3A5 *3 rs776746 GG carriers (197.3 vs 86.0, p < 0.001) had an almost twofold increase in the tacrolimus C 0 /D compared to that of the non-carriers. We further investigated the effect of the combination of recipient (intestinal) and donor (hepatic) genotypes on tacrolimus concentrations. Regardless of the genotype of the matched donor, CYP3A7 rs10211, CYP3A4*1G (rs2242480), and CYP3A5 *3 (rs776746) polymorphisms of recipients could affect tacrolimus concentrations. For the CYP3A4 rs4646437 polymorphisms, when the donor carried CYP3A4 rs4646437 CC, the recipient CYP3A4 rs4646437 polymorphism was associated with the C 0 /D of tacrolimus, and when the donor carried CYP3A4 rs4646437 CT/TT genotype, the recipient CYP3A4 rs4646437 polymorphism also affected on tacrolimus C 0 /D, although the effect was not significant. The large inter-individual variation in tacrolimus concentrations in the early stages after liver transplantation is influenced by genetic polymorphisms of CYP3A7 , CYP3A4 , and CYP3A5. Recipient (intestinal) CYP3A7 , CYP3A4 , and CYP3A5 polymorphisms seem to contribute more to such variation than donors. Therefore, the detection of CYP3A polymorphisms in recipients could help to predict the tacrolimus starting dose in the early stages after liver transplantation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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