| Literature DB >> 31624333 |
Ruben P A van Eijk1,2, Marinus J C Eijkemans2, Stavros Nikolakopoulos2, Marc D Jansen1, Henk-Jan Westeneng1, Kristel R van Eijk1, Rick A A van der Spek1, Joke J F A van Vugt1, Sanne Piepers3, Geert-Jan Groeneveld4, Jan H Veldink1, Leonard H van den Berg1, Michael A van Es5.
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.Entities:
Year: 2019 PMID： 31624333 DOI： 10.1038/s41397-019-0111-3
Source DB: PubMed Journal: Pharmacogenomics J ISSN： 1470-269X Impact factor: 3.550