RT Journal Article
T1 Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients.
A1 Sadovnick, A Dessa
A1 Traboulsee, Anthony L
A1 Bernales, Cecily Q
A1 Ross, Jay P
A1 Forwell, Amanda L
A1 Yee, Irene M
A1 Guillot-Noel, Lena
A1 Fontaine, Bertrand
A1 Cournu-Rebeix, Isabelle
A1 Alcina, Antonio
A1 Fedetz, Maria
A1 Izquierdo, Guillermo
A1 Matesanz, Fuencisla
A1 Hilven, Kelly
A1 Dubois, Benedicte
A1 Goris, An
A1 Astobiza, Ianire
A1 Alloza, Iraide
A1 Antigüedad, Alfredo
A1 Vandenbroeck, Koen
A1 Akkad, Denis A
A1 Aktas, Orhan
A1 Blaschke, Paul
A1 Buttmann, Mathias
A1 Chan, Andrew
A1 Epplen, Joerg T
A1 Gerdes, Lisa-Ann
A1 Kroner, Antje
A1 Kubisch, Christian
A1 Kümpfel, Tania
A1 Lohse, Peter
A1 Rieckmann, Peter
A1 Zettl, Uwe K
A1 Zipp, Frauke
A1 Bertram, Lars
A1 Lill, Christina M
A1 Fernandez, Oscar
A1 Urbaneja, Patricia
A1 Leyva, Laura
A1 Alvarez-Cermeño, Jose Carlos
A1 Arroyo, Rafael
A1 Garagorri, Aroa M
A1 Garcia-Martinez, Angel
A1 Villar, Luisa M
A1 Urcelay, Elena
A1 Malhotra, Sunny
A1 Montalban, Xavier
A1 Comabella, Manuel
A1 Berger, Thomas
A1 Fazekas, Franz
A1 Reindl, Markus
A1 Schmied, Mascha C
A1 Zimprich, Alexander
A1 Vilariño-Güell, Carles
K1 Association
K1 Genetics
K1 Linkage
K1 Multiple sclerosis
K1 Plasminogen
AB Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93-1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.
PB Oxford University Press
YR 2016
FD 2016-05-17
LK http://hdl.handle.net/10668/10099
UL http://hdl.handle.net/10668/10099
LA en
NO Sadovnick AD, Traboulsee AL, Bernales CQ, Ross JP, Forwell AL, Yee IM, et al. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients. G3 (Bethesda). 2016 Jul 7;6(7):2073-9
NO This research was undertaken thanks to funding from the Canada Research Chair [950-228408] and Canada Excellence Research Chair programs [214444], Canadian Institutes of Health Research [MOP-137051], Vancouver Coastal Health Research Institute, the Milan & Maureen Ilich Foundation [11-32095000], and the Vancouver Foundation [ADV14-1597]. Replication studies received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06. Fondo de Investigación Sanitaria (FIS)-Instituto de Salud Carlos III (ISCIII)-Fondos Europeos de Desarrollo Regional (FEDER), Unión Europea [grant numbers P12/00555, PI13/01527, PI13/01466 and PI13/0879 to F.M., A.A. and G.I.] and Junta de Andalucía -FEDER [grant number CTS2704 to F.M.]. B.D. is a Clinical Investigator of the Research Foundation Flanders (FWO-Vlaanderen). A.G. and B.D. are supported by the Research Fund KU Leuven (OT/11/087 and CREA/14/023) and the Research Foundation Flanders (G073415N).
DS RISalud
RD Apr 7, 2025