0 avis
Genetic factors implicated in the response to fingolimod treatment in multiple sclerosis patients: results from a pharmacogenetic meta-analysis
Archive ouverte
Edité par CCSD -
International audience. Background and aimsMultiple Sclerosis (MS) is a complex disease with high heterogeneity in terms of clinical presentation and treatment response. Pharmacogenetics can help to develop a more personalized approach and to improve disease management. We report the results of a GWAS on fingolimod-treated relapsing-remitting MS patients.MethodsWe included 4 cohorts of fingolimod-treated MS patients from San Raffaele Hospital, Milan, Italy (OSR1: 246 patients, OSR2: 98 patients), Brigham and Women's Hospital, Boston, USA (USA: 136 patients) and the Centre Hospitalier Universitaire de Toulouse, France (CHUT: 81 patients). We classified treatment response according to the NEDA (no evidence of disease activity) criterion at 2 years and time to first relapse (TFR). We performed a GWAS separately on each cohort and meta-analyzed them using a fixed-effect model.Resultsthree genome-wide significant variants were associated with TFR: rs9397818A on chr6 increases the risk of an earlier relapse and has an eQTL effect in whole blood on TFB1M, key to mitochondrial gene expression, and TIAM2, implicated in endothelial function and cell migration; rs2071572A is a risk allele intronic to synaptotagminV, involved in exocytosis of secretory vesicles, with an eQTL effect in brain cortex; finally the risk allele rs6124768A maps to CD40 locus and increases its expression according to a public eQTL database. No significant variants were identified in the NEDA analysis.Conclusionsgenetic variants possibly implicated in cell migration, neuronal functions and immune response were associated with response to fingolimod. Functional studies are ongoing.
Consulter en ligne
Suggestions
Du même auteur
