Pharmacogenetics may influence tacrolimus daily dose, but not urinary tubular damage markers in the long-term period after renal transplantation
Background: The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxid...
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| Format: | Article |
| Language: | English |
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Society of Medical Biochemists of Serbia, Belgrade
2015-01-01
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| Series: | Journal of Medical Biochemistry |
| Subjects: | |
| Online Access: | https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2015/1452-82581504422S.pdf |
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| author | Stefanović Nikola Z. Cvetković Tatjana P. Veličković-Radovanović Radmila M. Jevtović-Stoimenov Tatjana M. Vlahović Predrag M. Stojanović Ivana R. Pavlović Dušica D. |
| author_facet | Stefanović Nikola Z. Cvetković Tatjana P. Veličković-Radovanović Radmila M. Jevtović-Stoimenov Tatjana M. Vlahović Predrag M. Stojanović Ivana R. Pavlović Dušica D. |
| author_sort | Stefanović Nikola Z. |
| collection | DOAJ |
| description | Background: The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients. Methods: The study included 72 patients who were on TAC based immunosuppression. Allele-specific PCR was used for polymorphism determination. We measured the urinary thiobarbituric acid reactive substances (TBARS) and reactive carbonyl derivates (RCD) in order to evaluate oxidative injury, as well as the urinary activities of ectoenzymes (N-acetyl-b-Dglucosaminidase, aminopeptidase N and dipeptidyl peptidase IV) to evaluate tubular damage. Results: The carriers of CYP 3A5*1 allele required statistically higher daily doses of TAC than CYP *3/*3 carriers, as well as the carriers of C allele of ABCB1 gene compared to those with T T genotype. Also, there were no differences in TBARS, RCD and the activities of ectoenzymes between the patients' genotypes. Our results showed significant correlations between urinary TBARS and RCD and the ectoenzymes' activities. Conclusions: Our findings suggest that CYP 3A5 and ABCB1 3435 polymorphism may affect TAC daily doses, but not the drug's tubular toxicity. Furthermore, tubular damage may be associated with increased renal oxidative stress. |
| first_indexed | 2024-12-11T14:17:46Z |
| format | Article |
| id | doaj.art-e763df0d02ef4a42ade0b3d1574419a0 |
| institution | Directory Open Access Journal |
| issn | 1452-8258 1452-8266 |
| language | English |
| last_indexed | 2024-12-11T14:17:46Z |
| publishDate | 2015-01-01 |
| publisher | Society of Medical Biochemists of Serbia, Belgrade |
| record_format | Article |
| series | Journal of Medical Biochemistry |
| spelling | doaj.art-e763df0d02ef4a42ade0b3d1574419a02022-12-22T01:03:05ZengSociety of Medical Biochemists of Serbia, BelgradeJournal of Medical Biochemistry1452-82581452-82662015-01-013444224301452-82581504422SPharmacogenetics may influence tacrolimus daily dose, but not urinary tubular damage markers in the long-term period after renal transplantationStefanović Nikola Z.0https://orcid.org/0000-0003-2599-7508Cvetković Tatjana P.1Veličković-Radovanović Radmila M.2https://orcid.org/0000-0001-9055-3378Jevtović-Stoimenov Tatjana M.3Vlahović Predrag M.4Stojanović Ivana R.5Pavlović Dušica D.6University of Niš, Faculty of Medicine, Department of PharmacyUniversity of Niš, Faculty of Medicine, Institute of Biochemistry + Clinical Centre Niš, Clinic of NephrologyUniversity of Niš, Faculty of Medicine, Department of Pharmacy + Clinical Centre Niš, Clinic of NephrologyUniversity of Niš, Faculty of Medicine, Institute of BiochemistryClinical Centre Niš, Centre for Medical BiochemistryUniversity of Niš, Faculty of Medicine, Institute of BiochemistryUniversity of Niš, Faculty of Medicine, Institute of BiochemistryBackground: The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients. Methods: The study included 72 patients who were on TAC based immunosuppression. Allele-specific PCR was used for polymorphism determination. We measured the urinary thiobarbituric acid reactive substances (TBARS) and reactive carbonyl derivates (RCD) in order to evaluate oxidative injury, as well as the urinary activities of ectoenzymes (N-acetyl-b-Dglucosaminidase, aminopeptidase N and dipeptidyl peptidase IV) to evaluate tubular damage. Results: The carriers of CYP 3A5*1 allele required statistically higher daily doses of TAC than CYP *3/*3 carriers, as well as the carriers of C allele of ABCB1 gene compared to those with T T genotype. Also, there were no differences in TBARS, RCD and the activities of ectoenzymes between the patients' genotypes. Our results showed significant correlations between urinary TBARS and RCD and the ectoenzymes' activities. Conclusions: Our findings suggest that CYP 3A5 and ABCB1 3435 polymorphism may affect TAC daily doses, but not the drug's tubular toxicity. Furthermore, tubular damage may be associated with increased renal oxidative stress.https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2015/1452-82581504422S.pdfabcb1cyp3a5oxidative stressrenal transplantationtacrolimustubular damage |
| spellingShingle | Stefanović Nikola Z. Cvetković Tatjana P. Veličković-Radovanović Radmila M. Jevtović-Stoimenov Tatjana M. Vlahović Predrag M. Stojanović Ivana R. Pavlović Dušica D. Pharmacogenetics may influence tacrolimus daily dose, but not urinary tubular damage markers in the long-term period after renal transplantation Journal of Medical Biochemistry abcb1 cyp3a5 oxidative stress renal transplantation tacrolimus tubular damage |
| title | Pharmacogenetics may influence tacrolimus daily dose, but not urinary tubular damage markers in the long-term period after renal transplantation |
| title_full | Pharmacogenetics may influence tacrolimus daily dose, but not urinary tubular damage markers in the long-term period after renal transplantation |
| title_fullStr | Pharmacogenetics may influence tacrolimus daily dose, but not urinary tubular damage markers in the long-term period after renal transplantation |
| title_full_unstemmed | Pharmacogenetics may influence tacrolimus daily dose, but not urinary tubular damage markers in the long-term period after renal transplantation |
| title_short | Pharmacogenetics may influence tacrolimus daily dose, but not urinary tubular damage markers in the long-term period after renal transplantation |
| title_sort | pharmacogenetics may influence tacrolimus daily dose but not urinary tubular damage markers in the long term period after renal transplantation |
| topic | abcb1 cyp3a5 oxidative stress renal transplantation tacrolimus tubular damage |
| url | https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2015/1452-82581504422S.pdf |
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