title: Progranulin genetic polymorphisms influence progression of disability and relapse recovery in multiple sclerosis.
abstract: Progranulin (GRN) is a multifunctional protein involved in inflammation and repair, and also a neurotrophic factor critical for neuronal survival. Progranulin is strongly expressed in multiple sclerosis (MS) brains by macrophages and microglia.
  
  
  
  In this study we evaluated GRN genetic variability in 400 MS patients, in correlation with clinical variables such as disease severity and relapse recovery. We also evaluated serum progranulin levels in the different groups of GRN variants carriers.
  
  
  
  We found that incomplete recovery after a relapse is correlated with an increased frequency of the rs9897526 A allele (odds ratio (OR) 4.367, p = 0.005). A more severe disease course (Multiple Sclerosis Severity Score > 5) is correlated with an increased frequency of the rs9897526 A allele (OR 1.886, p = 0.002) and of the rs5848 T allele (OR 1.580, p = 0.019). Carriers of the variants associated with a more severe disease course (rs9897526 A, rs5848 T) have significantly lower levels of circulating progranulin (80.5 ± 9.1 ng/mL vs. 165.7 ng/mL, p = 0.01).
  
  
  
  GRN genetic polymorphisms likely influence disease course and relapse recovery in MS.
authors.affiliation: Neurologia 3 S.C., Department of Neuroscience, City of Health and Science University Hospital of Turin, Italy mvercellino@cittadellasalute.to.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Vercellino
authors.affiliation: Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.affiliation: Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.affiliation: Multiple Sclerosis Center, Department of Neuroscience, City of Health and Science University Hospital of Turin, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mattioda
authors.affiliation: Multiple Sclerosis Center, Department of Neuroscience, City of Health and Science University Hospital of Turin, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Chiavazza
authors.affiliation: Multiple Sclerosis Center, Department of Neuroscience, City of Health and Science University Hospital of Turin, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Binello
authors.affiliation: Multiple Sclerosis Center, Department of Neuroscience, City of Health and Science University Hospital of Turin, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pinessi
authors.affiliation: Neurologia 3 S.C., Department of Neuroscience, City of Health and Science University Hospital of Turin, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Giobbe
authors.affiliation: Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.affiliation: Multiple Sclerosis Center, Department of Neuroscience, City of Health and Science University Hospital of Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cavalla
mesh_terms: D000328:Adult; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics*; D007558:Italy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D000077153:Progranulins; D020127:Recovery of Function; D012008:Recurrence; D012307:Risk Factors
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
keywords: Multiple sclerosis; disability; genetic; inflammation; neuroprotection; progranulin; relapse