Impact of CYP3A5 genetic polymorphism on cross-reactivity in tacrolimus chemiluminescent immunoassay in kidney transplant recipients
| Autor: | Kumi Hirano, Takafumi Naito, Yasuaki Mino, Junichi Kawakami, Seiichiro Ozono, Tatsuya Takayama |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotype Clinical Biochemistry chemical and pharmacologic phenomena Pharmacology Cross Reactions medicine.disease_cause Biochemistry Gastroenterology Cross-reactivity Kidney transplant Tacrolimus Chemiluminescent immunoassay Internal medicine medicine Cytochrome P-450 CYP3A Humans CYP3A5 Kidney transplantation Immunoassay Polymorphism Genetic medicine.diagnostic_test business.industry Biochemistry (medical) General Medicine Middle Aged medicine.disease Kidney Transplantation surgical procedures operative Luminescent Measurements Female business Immunosuppressive Agents |
| Zdroj: | Clinica chimica acta; international journal of clinical chemistry. 414 |
| ISSN: | 1873-3492 |
| Popis: | Background Tacrolimus immunoassays possess cross-reactivity with metabolites in the blood. The aim of this study was to evaluate the cross-reactivity in tacrolimus chemiluminescent immunoassay (CLIA) in kidney transplant recipients and to characterize the cross-reactivity according to CYP3A5 genetic polymorphism. Methods The subjects were 50 kidney transplant recipients receiving low-dose tacrolimus. Blood levels of tacrolimus at 12 h (C12) measured by CLIA were compared with that by LC–MS/MS using Bland–Altman analysis. The influence of CYP3A5 genotypes on the cross-reactivity in tacrolimus CLIA was evaluated by interaction plots. Results No significant difference was observed in tacrolimus C12 between the CYP3A5*1/*3 and CYP3A5*3/*3 genotypes. The dose-normalized C12 of tacrolimus was significantly higher in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. The C12 ratio of 13-O-demethylate to tacrolimus was significantly lower in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. Tacrolimus C12 measured by CLIA was 35% higher than that by LC–MS/MS. A higher cross-reactivity was observed in the patients with a tacrolimus C12 of less than 3 μg/l and CYP3A5*1/*3 genotype. Conclusion This study confirmed the cross-reactivity in CLIA in kidney transplant recipients receiving low-dose tacrolimus. High metabolic capacity associated with the CYP3A5*1 genotype affected the cross-reactivity in patients with low tacrolimus levels. |
| Databáze: | OpenAIRE |
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