Impact of the CYP3A5, CYP3A4, COMT, IL-10 and POR Genetic Polymorphisms on Tacrolimus Metabolism in Chinese Renal Transplant Recipients
| Autor: | Wei-Mo Li, Xu-Hui Tan, Lin Zhou, Ping Zheng, Yan-Jun Zhang, Li Lin, Chuan-Jiang Li, Liang Li, Ze-Yan Zhong, Hai-Xia Jiang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Epidemiology medicine.medical_treatment lcsh:Medicine Gastroenterology Renal Transplantation Cytochrome P-450 CYP3A lcsh:Science Kidney transplantation Multidisciplinary Genomics Interleukin-10 Immunosuppressive drug surgical procedures operative Nephrology Medicine Female Immunosuppressive Agents Research Article Biotechnology Adult medicine.medical_specialty Drugs and Devices Single-nucleotide polymorphism Biology Catechol O-Methyltransferase Polymorphism Single Nucleotide Tacrolimus Pharmacokinetics Genomic Medicine Asian People Internal medicine medicine Genetics Humans CYP3A5 NADPH-Ferrihemoprotein Reductase Retrospective Studies Clinical Genetics Evolutionary Biology Population Biology Pharmacoepidemiology lcsh:R Computational Biology Retrospective cohort study medicine.disease Kidney Transplantation Transplantation Pharmacogenetics Immunology Genetic Polymorphism lcsh:Q Pharmacogenomics Population Genetics |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 1, p e86206 (2014) |
| ISSN: | 1932-6203 |
| Popis: | Tacrolimus is a widely used immunosuppressive drug for preventing the rejection of solid organ transplants. The efficacy of tacrolimus shows considerable variability, which might be related to genetic variation among recipients. We conducted a retrospective study of 240 Chinese renal transplant recipients receiving tacrolimus as immunosuppressive drug. The retrospective data of all patients were collected for 40 days after transplantation. Seventeen SNPs of CYP3A5, CYP3A4, COMT, IL-10 and POR were identified by the SNaPshot assay. Tacrolimus blood concentrations were obtained on days 1-3, days 6-8 and days 12-14 after transplantation, as well as during the period of the predefined therapeutic concentration range. Kruskal-Wallis test was used to examine the effect of genetic variation on the tacrolimus concentration/dose ratio (C 0/D) at different time points. Chi-square test was used to compare the proportions of patients who achieved the target C 0 range in the different genotypic groups at weeks 1, 2, 3 and 4 after transplantation. After correction for multiple testing, there was a significant association of C 0/D with CYP3A5*3, CYP3A4*1G and CYP3A4 rs4646437 T>C at different time points after transplantation. The proportion of patients in the IL-10 rs1800871-TT group who achieved the target C 0 range was greater (p = 0.004) compared to the IL-10 rs1800871-CT and IL-10 rs1800871-CC groups at week 3 after transplantation. CYP3A5*3, CYP3A4 *1G, CYP3A4 rs4646437 T>C and IL-10 rs1800871 C>T might be potential polymorphisms affecting the interindividual variability in tacrolimus metabolism among Chinese renal transplant recipients. |
| Databáze: | OpenAIRE |
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