TY - JOUR
T1 - Multiple Sclerosis Susceptibility Genes
T2 - Associations with Relapse Severity and Recovery
AU - Mowry, Ellen M.
AU - Carey, Robert F.
AU - Blasco, Maria R.
AU - Pelletier, Jean
AU - Duquette, Pierre
AU - Villoslada, Pablo
AU - Malikova, Irina
AU - Roger, Elaine
AU - Kinkel, R. Phillip
AU - McDonald, Jamie
AU - Bacchetti, Peter
AU - Waubant, Emmanuelle
N1 - Funding Information:
The authors have read the journal's policy and have the following conflicts: Dr. Mowry has received free medication from Teva Pharmaceuticals for an investigator-initiated clinical trial, of which she is Principal Investigator. Dr Pelletier has participated in Advisory Committees for several companies (Merck Serono, Bayer Schering, Biogen Idec, Sanofi Aventis, Teva, Novartis). He has received unrestricted research grants from Biogen Idec, Merck Serono, Bayer Schering, Novartis, and Sanofi Aventis. Dr. Duquette has participated in Advisory committees for several companies (Berlex, Biogen Idec, Serono, Novartis, and Teva Neurosciences) in the MS field and has been supported to attend MS meetings by the same companies. He has a research grant for an investigator-initiated study from Biogen Idec. Dr. Villoslada received consulting fees from Roche, Novartis, MedImmune, Neutotech Pharma, and Digna Biotech and is founder and holds stocks in Bionure Farma. Dr Kinkel has received honoraria as a consultant for Biogen Idec, Teva, Genzyme and Novartis. He has received research support from Biogen Idec. Dr. Waubant has received honoraria from Biogen Idec for 2 educational programs, and from Roche and Actelion as an ad-hoc consultant. She has received research support from Biogen Idec and Sanofi Aventis in the form of free medications for an ongoing trial. Co-author Pablo Villoslada is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
PY - 2013/10/9
Y1 - 2013/10/9
N2 - Objective:Patients with early multiple sclerosis (MS) have stereotyped attack severity and recovery. We sought to determine if polymorphisms in MS susceptibility genes are associated with these attack features or with the risk of a second attack.Methods:503 white subjects evaluated within a year of MS onset were included in the study. The severity of and recovery from the first two attacks were determined based on published definitions. Seventeen MS susceptibility genes were genotyped at the UCSF MS Genetics laboratory. Each polymorphism was evaluated in multivariate ordinal models, adjusted for the other polymorphisms, for its association with attack severity and recovery. We also assessed if these polymorphisms were associated with increased risk of a second attack.Results:The MPHOSPH9 polymorphism was associated with greater attack severity (odds ratios [OR] = 1.47, 95% CI [1.11, 1.94], p = 0.008), while the RGS1 and TNFRSF1A polymorphisms tended to be associated with reduced attack severity. The CD6 polymorphism tended to be associated with increased odds of worse attack recovery (OR = 1.25, 95% CI [0.93, 1.68], p = 0.13). In those who were HLA-DRB1-negative, the EVI5 polymorphism was associated with attacks of less severity; in HLA-DRB1 positive patients, EVI5 was associated with attacks of greater severity and worse recovery. The IL7R, TNFRSF1A, and GPC5 polymorphisms tended to be associated with having a second event within a year.Conclusions:Some MS susceptibility polymorphisms may be associated with attack severity, recovery, or frequency. Further characterization of these genes may lead to a better understanding of MS pathogenesis and to a more individualized treatment approach.
AB - Objective:Patients with early multiple sclerosis (MS) have stereotyped attack severity and recovery. We sought to determine if polymorphisms in MS susceptibility genes are associated with these attack features or with the risk of a second attack.Methods:503 white subjects evaluated within a year of MS onset were included in the study. The severity of and recovery from the first two attacks were determined based on published definitions. Seventeen MS susceptibility genes were genotyped at the UCSF MS Genetics laboratory. Each polymorphism was evaluated in multivariate ordinal models, adjusted for the other polymorphisms, for its association with attack severity and recovery. We also assessed if these polymorphisms were associated with increased risk of a second attack.Results:The MPHOSPH9 polymorphism was associated with greater attack severity (odds ratios [OR] = 1.47, 95% CI [1.11, 1.94], p = 0.008), while the RGS1 and TNFRSF1A polymorphisms tended to be associated with reduced attack severity. The CD6 polymorphism tended to be associated with increased odds of worse attack recovery (OR = 1.25, 95% CI [0.93, 1.68], p = 0.13). In those who were HLA-DRB1-negative, the EVI5 polymorphism was associated with attacks of less severity; in HLA-DRB1 positive patients, EVI5 was associated with attacks of greater severity and worse recovery. The IL7R, TNFRSF1A, and GPC5 polymorphisms tended to be associated with having a second event within a year.Conclusions:Some MS susceptibility polymorphisms may be associated with attack severity, recovery, or frequency. Further characterization of these genes may lead to a better understanding of MS pathogenesis and to a more individualized treatment approach.
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U2 - 10.1371/journal.pone.0075416
DO - 10.1371/journal.pone.0075416
M3 - Article
C2 - 24130709
AN - SCOPUS:84885350502
SN - 1932-6203
VL - 8
JO - PLoS One
JF - PLoS One
IS - 10
M1 - e75416
ER -