RESUMO
BACKGROUND: Tacrolimus (Tac) is mainly metabolized by cytochrome P450 3A isoenzymes. In a cohort of heart transplant recipients, we investigated the effect of CYP3A5, CYP3A4, and ABCB1/MDR1 polymorphisms on Tac dose requirements and the risk of developing new-onset diabetes after transplantation (NODAT). METHODS: A total of 65 heart transplant recipients were genotyped for 3 single nucleotide polymorphisms (SNPs) in the CYP3A5 (SNP rs776746), CYP3A4 (SNP rs2740574), and ABCB1 (SNP rs104564). The mean Tac dose values were compared between the genotypes. RESULTS: CYP3A5 3 homozygotes (nonexpressers; n = 55, 85%) received significantly higher Tac dose compared with CYP3A5 1 carriers (expressers). No different NODAT frequencies were found between the genotypes. CONCLUSIONS: The CYP3A5 polymorphism was the main determinant of Tac dose requirements among heart transplant recipients. This common functional polymorphism had no influence on the risk of developing NODAT.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Citocromo P-450 CYP3A/genética , Transplante de Coração/imunologia , Imunossupressores/administração & dosagem , Polimorfismo de Nucleotídeo Único , Tacrolimo/administração & dosagem , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adulto , Análise de Variância , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/genética , Feminino , Predisposição Genética para Doença , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Coração/efeitos adversos , Homozigoto , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/farmacocinética , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de Risco , Tacrolimo/efeitos adversos , Tacrolimo/farmacocinética , Resultado do Tratamento , Adulto JovemRESUMO
The chronic kidney disease-bone and mineral disorders (CKD-MBD) represents a dinamic area of research. Recently, new factors such as FGF-23 have been added to the classic list of regulators of bone metabolism, which include calcium, phosphorus, PTH and calcitriol. Vascular calcification, one of the most important complication of CKD-MBD is regulated by a complex variety of promoters and inhibitors. The relationship between vascular calcification, bone loss and mortality, together with the existence of likely common signaling pathways are subject of interesting investigations.
Assuntos
Osso e Ossos/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Nefropatias/complicações , Minerais/metabolismo , Calcitriol/fisiologia , Cálcio/metabolismo , Doença Crônica , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/fisiologia , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/metabolismo , Nefropatias/metabolismo , Nefropatias/mortalidade , Hormônio Paratireóideo/fisiologia , Fósforo/metabolismo , Calcificação Vascular/etiologia , Calcificação Vascular/metabolismoRESUMO
Las alteraciones del metabolismo óseo en el escenario de la enfermedad renal crónica (CKD-MBD) constituyen un dinámico campo de estudio. Al conjunto de reguladores clásicos del metabolismo óseo tales como calcio, fósforo, hormona paratiroidea (PTH) y calcitriol se ha añadido el factor de crecimiento fibroblástico 23 (FGF-23). La calcificación vascular, una de las complicaciones más importantes de la enfermedad renal crónica, está sujeta a una compleja regulación en la que intervienen factores promotores e inhibidores del proceso de mineralización. La asociación entre calcificación vascular, desmineralización ósea y mortalidad y la existencia de factores y vías de señalización comunes está siendo objeto de interesantes investigaciones (AU)
The chronic kidney disease-bone and mineral disorders (CKD-MBD) represents a dinamic area of research. Recently, new factors such as FGF-23 have been added to the classic list of regulators of bone metabolism, which include calcium, phosphorus, PTH and calcitriol. Vascular calcification, one of the most important complication of CKD-MBD is regulated by a complex variety of promoters and inhibitors. The relationship between vascular calcification, bone loss and mortality, together with the existence of likely common signaling pathways are subject of interesting investigations (AU)
