Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants
Cytochrome P450 (CYP) enzymes, such as <i>CYP3A4,</i> and <i>CYP3A5</i>, P450 oxidoreductase (POR), peroxisome proliferator activated receptor alpha (PPAR-alpha), and drug transporter (ABCB1) were observed to influence concentrations of immunosuppressants (cyclosporine, evero...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/5/823 |
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| author | Kannan Sridharan Shamik Shah Anfal Jassim Mona Hammad Johaina Ebrahim Al Gadhban Ola Al Segai |
| author_facet | Kannan Sridharan Shamik Shah Anfal Jassim Mona Hammad Johaina Ebrahim Al Gadhban Ola Al Segai |
| author_sort | Kannan Sridharan |
| collection | DOAJ |
| description | Cytochrome P450 (CYP) enzymes, such as <i>CYP3A4,</i> and <i>CYP3A5</i>, P450 oxidoreductase (POR), peroxisome proliferator activated receptor alpha (PPAR-alpha), and drug transporter (ABCB1) were observed to influence concentrations of immunosuppressants (cyclosporine, everolimus, sirolimus, and tacrolimus) and outcomes in renal transplants. We carried out the present study to evaluate the prevalence and impact of these single nucleotide polymorphisms (SNPs) in adult renal transplants. SNPs were evaluated using commercial TaqMan<sup>®</sup> assays. Serum drug concentrations were estimated using immunoassays. One hundred and forty-six patients were recruited. SNPs in <i>CYP3A5*3</i> were significantly associated with greater dose-adjusted cyclosporine and tacrolimus concentrations. SNPs in <i>POR*28</i> were observed with significantly lower dose-adjusted concentrations, particularly with cyclosporine and tacrolimus. <i>ABCB1</i> homozygous polymorphisms were observed with significantly lower time spent in the therapeutic range with cyclosporine and everolimus/sirolimus. Cyclosporine was observed in a significantly greater proportion of patients with elevated GGT, and SNPs in <i>PPAR-alpha</i> were significantly associated with an increased risk of this adverse event. Hypertriglyceridemia with everolimus was significantly associated with <i>POR*28</i> polymorphisms. There is a need to validate the influence of these SNPs in a prospective study and develop an algorithm predicting the achievement of target concentrations. |
| first_indexed | 2024-03-10T03:35:51Z |
| format | Article |
| id | doaj.art-95d9c46d11814b68a854abd83f259137 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T03:35:51Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-95d9c46d11814b68a854abd83f2591372023-11-23T11:45:23ZengMDPI AGJournal of Personalized Medicine2075-44262022-05-0112582310.3390/jpm12050823Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving ImmunosuppressantsKannan Sridharan0Shamik Shah1Anfal Jassim2Mona Hammad3Johaina Ebrahim Al Gadhban4Ola Al Segai5Department of Pharmacology & Therapeutics, College of Medicine & Medical Sciences, Arabian Gulf University, Manama 328, BahrainDepartment of Nephrology, Salmaniya Medical Complex, Manama 328, BahrainDepartment of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama 328, BahrainSalmaniya Medical Complex, Manama 328, BahrainDepartment of Nephrology, Salmaniya Medical Complex, Manama 328, BahrainDepartment of Biochemistry, Salmaniya Medical Complex, Manama 328, BahrainCytochrome P450 (CYP) enzymes, such as <i>CYP3A4,</i> and <i>CYP3A5</i>, P450 oxidoreductase (POR), peroxisome proliferator activated receptor alpha (PPAR-alpha), and drug transporter (ABCB1) were observed to influence concentrations of immunosuppressants (cyclosporine, everolimus, sirolimus, and tacrolimus) and outcomes in renal transplants. We carried out the present study to evaluate the prevalence and impact of these single nucleotide polymorphisms (SNPs) in adult renal transplants. SNPs were evaluated using commercial TaqMan<sup>®</sup> assays. Serum drug concentrations were estimated using immunoassays. One hundred and forty-six patients were recruited. SNPs in <i>CYP3A5*3</i> were significantly associated with greater dose-adjusted cyclosporine and tacrolimus concentrations. SNPs in <i>POR*28</i> were observed with significantly lower dose-adjusted concentrations, particularly with cyclosporine and tacrolimus. <i>ABCB1</i> homozygous polymorphisms were observed with significantly lower time spent in the therapeutic range with cyclosporine and everolimus/sirolimus. Cyclosporine was observed in a significantly greater proportion of patients with elevated GGT, and SNPs in <i>PPAR-alpha</i> were significantly associated with an increased risk of this adverse event. Hypertriglyceridemia with everolimus was significantly associated with <i>POR*28</i> polymorphisms. There is a need to validate the influence of these SNPs in a prospective study and develop an algorithm predicting the achievement of target concentrations.https://www.mdpi.com/2075-4426/12/5/823sirolimustacrolimuscyclosporine |
| spellingShingle | Kannan Sridharan Shamik Shah Anfal Jassim Mona Hammad Johaina Ebrahim Al Gadhban Ola Al Segai Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants Journal of Personalized Medicine sirolimus tacrolimus cyclosporine |
| title | Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants |
| title_full | Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants |
| title_fullStr | Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants |
| title_full_unstemmed | Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants |
| title_short | Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants |
| title_sort | evaluation of pharmacogenetics of drug metabolizing enzymes and drug efflux transporter in renal transplants receiving immunosuppressants |
| topic | sirolimus tacrolimus cyclosporine |
| url | https://www.mdpi.com/2075-4426/12/5/823 |
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