Pharmacogenetic study of long-term response to interferon-ß treatment in multiple sclerosis.
Pharmacogenomics J
; 17(1): 84-91, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-26644207
ABSTRACT
The aim of the study is the identification of genetic factors that influence the long-term response to interferon-ß (IFNß) (4-year follow-up). We performed a genome-wide association study in 337 IFNß-treated Italian multiple sclerosis patients at the extreme of treatment response, and we meta-analyzed association effects, integrating results with pathway analysis, gene-expression profiling of IFNß-stimulated peripheral blood mononuclear cells from 20 healthy controls (HC) and expression quantitative locus (eQTL) analyses. From meta-analysis, 43 markers were associated at P<10-4, and two of them (rs7298096 and rs4726460) pointed to two genes, NINJ2 and TBXAS1, that were significantly downregulated after IFNß stimulation in HC (P=3.1 × 10-9 and 5.6 × 10-10). We also observed an eQTL effect for the allele associated with favorable treatment response (rs4726460A); moreover, TBXAS1 appeared downregulated upon IFNß administration (ß=-0.39; P=0.02). Finally, we found an enrichment of pathways related to inflammatory processes and presynaptic membrane, the latter with involvement of genes related to glutamatergic system (GRM3 and GRIK2), confirming its potential role in the response to IFNß.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Farmacogenética
/
Interferon beta
/
Polimorfismo de Nucleotídeo Único
/
Variantes Farmacogenômicos
/
Fatores Imunológicos
/
Esclerose Múltipla
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Pharmacogenomics J
Assunto da revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Itália