Marco Vercellino1, Chiara Fenoglio2, Daniela Galimberti2, Alessandra Mattioda3, Carlotta Chiavazza3, Eleonora Binello3, Lorenzo Pinessi3, Dario Giobbe4, Elio Scarpini2, Paola Cavalla3. 1. Neurologia 3 S.C., Department of Neuroscience, City of Health and Science University Hospital of Turin, Italy mvercellino@cittadellasalute.to.it. 2. Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Italy. 3. Multiple Sclerosis Center, Department of Neuroscience, City of Health and Science University Hospital of Turin, Italy. 4. Neurologia 3 S.C., Department of Neuroscience, City of Health and Science University Hospital of Turin, Italy.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: GRN genetic polymorphisms likely influence disease course and relapse recovery in MS.
BACKGROUND: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. METHODS: 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. RESULTS: 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). CONCLUSION:GRN genetic polymorphisms likely influence disease course and relapse recovery in MS.
Authors: Lieke H H Meeter; Holger Patzke; Gordon Loewen; Elise G P Dopper; Yolande A L Pijnenburg; Rick van Minkelen; John C van Swieten Journal: Dement Geriatr Cogn Dis Extra Date: 2016-07-22
Authors: Pablo L Cardozo; Izabella B Q de Lima; Esther M A Maciel; Nathália C Silva; Tomas Dobransky; Fabíola M Ribeiro Journal: Curr Neuropharmacol Date: 2019 Impact factor: 7.363
Authors: Emmanuelle Waubant; Robyn Lucas; Ellen Mowry; Jennifer Graves; Tomas Olsson; Lars Alfredsson; Annette Langer-Gould Journal: Ann Clin Transl Neurol Date: 2019-08-07 Impact factor: 4.511