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Abstract
Background: Tarolimus (Tac), a calcineurin inhibitor, is the cornerstone of most immunosuppressive regimens following renal transplantation. Tac metabolism is closely related to the presence of the enzyme CYP3A5 in the liver and intestines. The study aimed to determine the CYP3A5 genetic polymorphism and the relationship between dose and trough concentration (C0) Tac as well as intrapatient variability of tacrolimus (IPV Tac) with CYP3A5 polymorphism.
Methods: 76 kidney transplant patients from living donors at the Department of Nephrology and Transplant Immunology, People’s Hospital 115, from December 2018 to May 2021, were sequenced for the CYP3A5 gene and had at least 3 C0 Tac from 7th to 12th month post-transplant were included in the study. Simultaneously we recorded the Tac dose and IPV Tac from the 7th to the 12th month post - transplant.
Results: The proportions of genotypes CYP3A5/1*1, /1*3 (expresser group) and /3*3 (non - expresser group) were 11.8%, 32.9% and 55.3%, respectively. There were no differences in CYP3A5 genotypes between males and females. The mean Tac dose was higher significant in the expresser group (6,36 ± 0,4mg) compared with the non - expresser group (3,94 ± 0,27mg) (p = 0.001), while the mean C0 Tac was lower in the expresser group (8,08 ± 0,29 ng/mL) compared with the non - expresser group (99,34 ± 0,31 ng/mL) (p = 0.008). The mean IPV Tac was 17.9 ± 9.7% (range 3.4% - 55.8%). IPV Tac was not statistically significant between groups with and without CYP3A5 expression due to the small sample size and most patients with low IPV Tac (< 20%).
Conclusion: Expression of CYP3A5 enzyme (in genotypes CYP3A5/1*1 and /1*3) is very common (1 in 2 kidney transplant patients) and affects dose and Tac concentration in kidney transplant patients.
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| Published | 13-12-2023 | |
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| Issue | No. 93 (2024) | |
| Section | Original article | |
| DOI | 10.38103/jcmhch.93.9 | |
| Keywords | Ghép thận, Tacrolimus, CYP3A5, Biến thiên nội tại nồng độ đáy Tacrolimus Kidney transplantation, Tacrolimus, CYP3A5, Intrapatient variability of trough tacrolimus concentrations |
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