Pharmacogenetic interactions in amyotrophic lateral sclerosis: a step closer to a cure?
Pharmacogenomics J
; 20(2): 220-226, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-31624333
ABSTRACT
Genetic mutations related to amyotrophic lateral sclerosis (ALS) act through distinct pathophysiological pathways, which may lead to varying treatment responses. Here we assess the genetic interaction between C9orf72, UNC13A, and MOBP with creatine and valproic acid treatment in two clinical trials. Genotypic data was available for 309 of the 338 participants (91.4%). The UNC13A genotype affected mortality (p = 0.012), whereas C9orf72 repeat-expansion carriers exhibited a faster rate of decline in overall (p = 0.051) and bulbar functioning (p = 0.005). A dose-response pharmacogenetic interaction was identified between creatine and the A allele of the MOBP genotype (p = 0.027), suggesting a qualitative interaction in a recessive model (HR 3.96, p = 0.015). Not taking genetic information into account may mask evidence of response to treatment or be an unrecognized source of bias. Incorporating genetic data could help investigators to identify critical treatment clues in patients with ALS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Farmacogenética
/
Epistasia Genética
/
Proteína C9orf72
/
Esclerose Lateral Amiotrófica
/
Proteínas da Mielina
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
/
Qualitative_research
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Pharmacogenomics J
Assunto da revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Holanda