Cytochrome P450 genetic polymorphisms influence the serum concentration of calcineurin inhibitors in allogeneic hematopoietic SCT recipients
| Autor: | Daisuke Ohgiya, Masako Toyosaki, Hiroshi Kawada, Kiyoshi Ando, Hidetoshi Inoko, Sinichiro Machida, M Onizuka, Y Ogawa, Nanae Kunii |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Drug
Adult Male Genotype media_common.quotation_subject Calcineurin Inhibitors Graft vs Host Disease CYP2C19 Pharmacology Polymorphism Single Nucleotide Tacrolimus Cytochrome P-450 Enzyme System Medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Enzyme Inhibitors CYP3A5 media_common Transplantation biology business.industry Hematopoietic Stem Cell Transplantation Cytochrome P450 Hematology Middle Aged Calcineurin Haematopoiesis surgical procedures operative biology.protein Cyclosporine Female business Immunosuppressive Agents |
| Zdroj: | Bone marrow transplantation. 46(8) |
| ISSN: | 1476-5365 |
| Popis: | Calcineurin inhibitors are necessary as immunosuppressants during hematopoietic SCT (HSCT) to prevent alloreactivity, but have unfortunate toxicities. So, we investigated the association of gene polymorphisms with the initial calcineurin inhibitor concentration and the subsequent drug dose from day 1 to day 28 among patients who underwent HSCT at a single institution. We analyzed 58 serial cases of Japanese patients receiving GVHD prophylaxis with CsA (21 cases) or tacrolimus (37 cases). We investigated eight single-nucleotide polymorphisms: rs4244285 (CYP2C19), rs15524, rs4646450, rs3800959, rs776746 (CYP3A5), rs1128503, rs2032582 and rs1045642 (MDR1). The CsA concentration was significantly higher when the genotype of CYP3A5 rs15524 was T/T (P=0.044) or rs776746 was G/G (P=0.027). The CYP3A5 rs776746 and rs4646450 genotypes were also associated with tacrolimus concentration (P=0.013 and P=0.0058, respectively). The dosage of tacrolimus was remarkably reduced from day -1 to day 28 when the patient had the CYP3A5 rs4646450 C/C and/or rs776746 G/G genotype (P=0.0010 and P=0.0021, respectively). In this study, we show that genetic variation has a predictable effect on the pharmacological responses to calcineurin inhibitors in HSCT patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|