Research ExplorerPublicationsAnalysis of Plasminogen Genetic Variants in Multiple Scleros...

Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients

Standard

Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients. / Sadovnick, A Dessa; Traboulsee, Anthony L; Bernales, Cecily Q; Ross, Jay P; Forwell, Amanda L; Yee, Irene M; Guillot-Noel, Lena; Fontaine, Bertrand; Cournu-Rebeix, Isabelle; Alcina, Antonio; Fedetz, Maria; Izquierdo, Guillermo; Matesanz, Fuencisla; Hilven, Kelly; Dubois, Bénédicte; Goris, An; Astobiza, Ianire; Alloza, Iraide; Antigüedad, Alfredo; Vandenbroeck, Koen; Akkad, Denis A; Aktas, Orhan; Blaschke, Paul; Buttmann, Mathias; Chan, Andrew; Epplen, Joerg T; Gerdes, Lisa-Ann; Kroner, Antje; Kubisch, Christian; Kümpfel, Tania; Lohse, Peter; Rieckmann, Peter; Zettl, Uwe K; Zipp, Frauke; Bertram, Lars; Lill, Christina M; Fernandez, Oscar; Urbaneja, Patricia; Leyva, Laura; Alvarez-Cermeño, Jose Carlos; Arroyo, Rafael; Garagorri, Aroa M; García-Martínez, Angel; Villar, Luisa M; Urcelay, Elena; Malhotra, Sunny; Montalban, Xavier; Comabella, Manuel; Berger, Thomas; Fazekas, Franz; Reindl, Markus; Schmied, Mascha C; Zimprich, Alexander; Vilariño-Güell, Carles.

In: G3-GENES GENOM GENET, Vol. 6, No. 7, 07.07.2016, p. 2073-9.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sadovnick, AD, Traboulsee, AL, Bernales, CQ, Ross, JP, Forwell, AL, Yee, IM, Guillot-Noel, L, Fontaine, B, Cournu-Rebeix, I, Alcina, A, Fedetz, M, Izquierdo, G, Matesanz, F, Hilven, K, Dubois, B, Goris, A, Astobiza, I, Alloza, I, Antigüedad, A, Vandenbroeck, K, Akkad, DA, Aktas, O, Blaschke, P, Buttmann, M, Chan, A, Epplen, JT, Gerdes, L-A, Kroner, A, Kubisch, C, Kümpfel, T, Lohse, P, Rieckmann, P, Zettl, UK, Zipp, F, Bertram, L, Lill, CM, Fernandez, O, Urbaneja, P, Leyva, L, Alvarez-Cermeño, JC, Arroyo, R, Garagorri, AM, García-Martínez, A, Villar, LM, Urcelay, E, Malhotra, S, Montalban, X, Comabella, M, Berger, T, Fazekas, F, Reindl, M, Schmied, MC, Zimprich, A & Vilariño-Güell, C 2016, 'Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients', G3-GENES GENOM GENET, vol. 6, no. 7, pp. 2073-9. https://doi.org/10.1534/g3.116.030841

APA

Sadovnick, A. D., Traboulsee, A. L., Bernales, C. Q., Ross, J. P., Forwell, A. L., Yee, I. M., Guillot-Noel, L., Fontaine, B., Cournu-Rebeix, I., Alcina, A., Fedetz, M., Izquierdo, G., Matesanz, F., Hilven, K., Dubois, B., Goris, A., Astobiza, I., Alloza, I., Antigüedad, A., ... Vilariño-Güell, C. (2016). Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients. G3-GENES GENOM GENET, 6(7), 2073-9. https://doi.org/10.1534/g3.116.030841

Vancouver

Sadovnick AD, Traboulsee AL, Bernales CQ, Ross JP, Forwell AL, Yee IM et al. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients. G3-GENES GENOM GENET. 2016 Jul 7;6(7):2073-9. https://doi.org/10.1534/g3.116.030841

Bibtex

@article{a071deb3ad9542e3ae47217677263025,
title = "Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients",
abstract = "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.",
keywords = "Journal Article",
author = "Sadovnick, {A Dessa} and Traboulsee, {Anthony L} and Bernales, {Cecily Q} and Ross, {Jay P} and Forwell, {Amanda L} and Yee, {Irene M} and Lena Guillot-Noel and Bertrand Fontaine and Isabelle Cournu-Rebeix and Antonio Alcina and Maria Fedetz and Guillermo Izquierdo and Fuencisla Matesanz and Kelly Hilven and B{\'e}n{\'e}dicte Dubois and An Goris and Ianire Astobiza and Iraide Alloza and Alfredo Antig{\"u}edad and Koen Vandenbroeck and Akkad, {Denis A} and Orhan Aktas and Paul Blaschke and Mathias Buttmann and Andrew Chan and Epplen, {Joerg T} and Lisa-Ann Gerdes and Antje Kroner and Christian Kubisch and Tania K{\"u}mpfel and Peter Lohse and Peter Rieckmann and Zettl, {Uwe K} and Frauke Zipp and Lars Bertram and Lill, {Christina M} and Oscar Fernandez and Patricia Urbaneja and Laura Leyva and Alvarez-Cerme{\~n}o, {Jose Carlos} and Rafael Arroyo and Garagorri, {Aroa M} and Angel Garc{\'i}a-Mart{\'i}nez and Villar, {Luisa M} and Elena Urcelay and Sunny Malhotra and Xavier Montalban and Manuel Comabella and Thomas Berger and Franz Fazekas and Markus Reindl and Schmied, {Mascha C} and Alexander Zimprich and Carles Vilari{\~n}o-G{\"u}ell",
note = "Copyright {\textcopyright} 2016 Sadovnick et al.",
year = "2016",
month = jul,
day = "7",
doi = "10.1534/g3.116.030841",
language = "English",
volume = "6",
pages = "2073--9",
journal = "G3-GENES GENOM GENET",
issn = "2160-1836",
publisher = "Genetics Society of America",
number = "7",

}

RIS

TY - JOUR

T1 - Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients

AU - Sadovnick, A Dessa

AU - Traboulsee, Anthony L

AU - Bernales, Cecily Q

AU - Ross, Jay P

AU - Forwell, Amanda L

AU - Yee, Irene M

AU - Guillot-Noel, Lena

AU - Fontaine, Bertrand

AU - Cournu-Rebeix, Isabelle

AU - Alcina, Antonio

AU - Fedetz, Maria

AU - Izquierdo, Guillermo

AU - Matesanz, Fuencisla

AU - Hilven, Kelly

AU - Dubois, Bénédicte

AU - Goris, An

AU - Astobiza, Ianire

AU - Alloza, Iraide

AU - Antigüedad, Alfredo

AU - Vandenbroeck, Koen

AU - Akkad, Denis A

AU - Aktas, Orhan

AU - Blaschke, Paul

AU - Buttmann, Mathias

AU - Chan, Andrew

AU - Epplen, Joerg T

AU - Gerdes, Lisa-Ann

AU - Kroner, Antje

AU - Kubisch, Christian

AU - Kümpfel, Tania

AU - Lohse, Peter

AU - Rieckmann, Peter

AU - Zettl, Uwe K

AU - Zipp, Frauke

AU - Bertram, Lars

AU - Lill, Christina M

AU - Fernandez, Oscar

AU - Urbaneja, Patricia

AU - Leyva, Laura

AU - Alvarez-Cermeño, Jose Carlos

AU - Arroyo, Rafael

AU - Garagorri, Aroa M

AU - García-Martínez, Angel

AU - Villar, Luisa M

AU - Urcelay, Elena

AU - Malhotra, Sunny

AU - Montalban, Xavier

AU - Comabella, Manuel

AU - Berger, Thomas

AU - Fazekas, Franz

AU - Reindl, Markus

AU - Schmied, Mascha C

AU - Zimprich, Alexander

AU - Vilariño-Güell, Carles

N1 - Copyright © 2016 Sadovnick et al.

PY - 2016/7/7

Y1 - 2016/7/7

N2 - 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.

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.

KW - Journal Article

U2 - 10.1534/g3.116.030841

DO - 10.1534/g3.116.030841

M3 - SCORING: Journal article

C2 - 27194806

VL - 6

SP - 2073

EP - 2079

JO - G3-GENES GENOM GENET

JF - G3-GENES GENOM GENET

SN - 2160-1836

IS - 7

ER -