Response to interferon-beta treatment in multiple sclerosis patients: a genome-wide association study.
Pharmacogenomics J
; 17(4): 312-318, 2017 07.
Article
em En
| MEDLINE
| ID: mdl-27001119
ABSTRACT
Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-ß) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-ß treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-ß-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 10-6) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10-5) and near ZNF697 (combined P-value 8.15 × 10-5).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interferon beta
/
Esclerose Múltipla
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
País como assunto:
Europa
/
Oceania
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article