Genetic Variants Associated With Immunosuppressant Pharmacokinetics and Adverse Effects in the DeKAF Genomics Genome-wide Association Studies.
Transplantation
; 103(6): 1131-1139, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30801552
ABSTRACT
BACKGROUND:
The immunosuppressants tacrolimus and mycophenolate are important components to the success of organ transplantation, but are also associated with adverse effects, such as nephrotoxicity, anemia, leukopenia, and new-onset diabetes after transplantation. In this report, we attempted to identify genetic variants which are associated with these adverse outcomes.METHODS:
We performed a genome-wide association study, using a genotyping array tailored specifically for transplantation outcomes containing 722 147 single nucleotide polymorphisms, and 2 cohorts of kidney allograft recipients-a discovery cohort and a confirmation cohort-to identify and then confirm genetic variants associated with immunosuppressant pharmacokinetics and adverse outcomes.RESULTS:
Several genetic variants were found to be associated with tacrolimus trough concentrations. We did not confirm variants associated with the other phenotypes tested although several suggestive variants were identified.CONCLUSIONS:
These results show that adverse effects associated with tacrolimus and mycophenolate are complex, and recipient risk is not determined by a few genetic variants with large effects with but most likely are due to many variants, each with small effect sizes, and clinical factors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
1_ASSA2030
/
2_ODS3
Problema de saúde:
1_doencas_nao_transmissiveis
/
2_muertes_prematuras_enfermedades_notrasmisibles
Assunto principal:
Transplante de Rim
/
Tacrolimo
/
Polimorfismo de Nucleotídeo Único
/
Variantes Farmacogenômicos
/
Imunossupressores
/
Ácido Micofenólico
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Transplantation
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Mongólia