The role of HLA genes in pharmacogenomics: unravelling HLA associated adverse drug reactions.
Immunogenetics
; 69(8-9): 617-630, 2017 08.
Article
en En
| MEDLINE
| ID: mdl-28695285
ABSTRACT
Genetic polymorphism in the genes encoding the human leukocyte antigen (HLA) molecules enables presentation of a wide range peptide ligands thus maximising immune surveillance of pathogens. A consequence of the diversification of the HLA Ag-binding pocket is the enhanced opportunity for off-target binding of small drugs by HLA molecules, with subsequent immune reactivity. These potential off-target interactions are 'set up' to generate T cell-mediated adverse drug reactions even though the precise mechanisms of most HLA-drug interactions are still poorly understood. The association between abacavir hypersensitivity syndrome and HLA-B*5701 is one exception that has been resolved at a molecular and mechanistic level. Here, we explore the road to understanding the interaction between abacavir and the HLA-B*5701 molecule and review the current state of understanding of interactions between other drugs and HLA molecules implicated in adverse drug reactions, which appear to involve multiple mechanisms. The continued expansion of the pharmacopoeia generates an imperative to understand these interactions at the molecular level in order to prevent the continued burden on individuals and the health care system.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Farmacogenética
/
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos
/
Antígenos HLA
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Immunogenetics
Año:
2017
Tipo del documento:
Article
País de afiliación:
Australia