Donor and recipient P450 gene polymorphisms influence individual pharmacological effects of tacrolimus in Chinese liver transplantation patients
| Autor: | Huan Liu, Xiaoyue Fu, Bo Yao, Dongdong Lin, Yabo Ouyang, Dexi Chen, Zhiqiang Li, Jianyu Liu, Yunjin Zang |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Graft Rejection Male China medicine.medical_specialty Adolescent Genotype medicine.medical_treatment Immunology Single-nucleotide polymorphism Liver transplantation Polymorphism Single Nucleotide 030226 pharmacology & pharmacy Gastroenterology Tacrolimus Young Adult 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Cytochrome P-450 CYP3A Humans Immunology and Allergy CYP3A5 Alleles Aged Pharmacology biology business.industry Graft Survival Cytochrome P450 Middle Aged Tissue Donors Liver Transplantation Transplantation Treatment Outcome Histocompatibility 030220 oncology & carcinogenesis Pharmacogenomics biology.protein Female business Immunosuppressive Agents |
| Zdroj: | International Immunopharmacology. 57:18-24 |
| ISSN: | 1567-5769 |
| Popis: | The immunosuppressant drug tacrolimus (Tac) used for the prevention of immunological rejection is a metabolic substrate of cytochrome P450 enzymes. This study was designed to evaluate the short-term and long-term potential influence of single-nucleotide polymorphisms (SNPs) in CYP450 genes of liver transplant (LT) recipients as well as the donors on individual pharmacological effects of Tac and to guide individualized-medication from the perspective of pharmacogenomics. Twenty-one SNPs of the CYP450 gene were genotyped for both recipients and donors in 373 LT patients receiving Tac-based immunosuppressants. The Tac concentration/dosage ratio (C/D) was evaluated from the initial medication until one year after LT. The C/D ratio was significantly higher when the donor and/or recipient genotype of CYP3A5 rs776746 was G/G or rs15524 was T/T or rs4646450 was C/C all through one year after transplantation. Comparing the effect of donor gene variants of rs776746, rs15524, and rs4646450 on Tac C/D ratios with the recipients, statistically significant differences were found between the donor T/T group and the recipient T/T group in rs15524 at 1 month and 6 months, and at 6 months, the donor C/C group differed from the recipient C/C group in rs4646450. In conclusion, rs776746, rs15524, and rs4646450 of CYP3A5 had a significant influence on Tac pharmacological effects for both the initial use and long-term use. The donor liver genotype and the recipient intestine genotype contribute almost equally in the short-term, but the donor genotype had a greater effect than the recipient genotype at 6 months. Personalized Tac treatment after LT should be based on the CYP3A5 genotype. |
| Databáze: | OpenAIRE |
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