Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis.


Journal

Multiple sclerosis (Houndmills, Basingstoke, England)
ISSN: 1477-0970
Titre abrégé: Mult Scler
Pays: England
ID NLM: 9509185

Informations de publication

Date de publication:
04 2019
Historique:
pubmed: 14 3 2018
medline: 28 3 2020
entrez: 14 3 2018
Statut: ppublish

Résumé

The course of multiple sclerosis (MS) shows substantial inter-individual variability. The underlying determinants of disease severity likely involve genetic and environmental factors. The aim of this study was to assess the impact of APOE and HLA polymorphisms as well as smoking and body mass index (BMI) in the very early MS course. Untreated patients ( n = 263) with a recent diagnosis of relapsing-remitting (RR) MS or clinically isolated syndrome underwent standardized magnetic resonance imaging (MRI). Genotyping was performed for single-nucleotide polymorphisms (SNPs) rs3135388 tagging the HLA-DRB1*15:01 haplotype and rs7412 (Ɛ2) and rs429358 (Ɛ4) in APOE. Linear regression analyses were applied based on the three SNPs, smoking and BMI as exposures and MRI surrogate markers for disease severity as outcomes. Current smoking was associated with reduced gray matter fraction, lower brain parenchymal fraction and increased cerebrospinal fluid fraction in comparison to non-smoking, whereas no effect was observed on white matter fraction. BMI and the SNPs in HLA and APOE were not associated with structural MRI parameters. Smoking may have an unfavorable effect on the gray matter fraction as a potential measure of MS severity already in early MS. These findings may impact patients' counseling upon initial diagnosis of MS.

Sections du résumé

BACKGROUND
The course of multiple sclerosis (MS) shows substantial inter-individual variability. The underlying determinants of disease severity likely involve genetic and environmental factors.
OBJECTIVE
The aim of this study was to assess the impact of APOE and HLA polymorphisms as well as smoking and body mass index (BMI) in the very early MS course.
METHODS
Untreated patients ( n = 263) with a recent diagnosis of relapsing-remitting (RR) MS or clinically isolated syndrome underwent standardized magnetic resonance imaging (MRI). Genotyping was performed for single-nucleotide polymorphisms (SNPs) rs3135388 tagging the HLA-DRB1*15:01 haplotype and rs7412 (Ɛ2) and rs429358 (Ɛ4) in APOE. Linear regression analyses were applied based on the three SNPs, smoking and BMI as exposures and MRI surrogate markers for disease severity as outcomes.
RESULTS
Current smoking was associated with reduced gray matter fraction, lower brain parenchymal fraction and increased cerebrospinal fluid fraction in comparison to non-smoking, whereas no effect was observed on white matter fraction. BMI and the SNPs in HLA and APOE were not associated with structural MRI parameters.
CONCLUSIONS
Smoking may have an unfavorable effect on the gray matter fraction as a potential measure of MS severity already in early MS. These findings may impact patients' counseling upon initial diagnosis of MS.

Identifiants

pubmed: 29532745
doi: 10.1177/1352458518763541
doi:

Substances chimiques

Apolipoproteins E 0
HLA-DRB1 Chains 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

661-668

Auteurs

Christiane Graetz (C)

Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Adriane Gröger (A)

Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Felix Luessi (F)

Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Anke Salmen (A)

Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany; Department of Neurology, Bern University Hospital, University of Bern, Bern, Switzerland.

Daniela Zöller (D)

Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany/Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.

Janine Schultz (J)

Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Nelly Siller (N)

Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Vinzenz Fleischer (V)

Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Barbara Bellenberg (B)

Department of Radiology and Nuclear Medicine, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.

Achim Berthele (A)

Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Viola Biberacher (V)

Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany/TUM-NIC Neuroimaging Center, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Joachim Havla (J)

Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany.

Michael Hecker (M)

Department of Neurology, University of Rostock, Rostock, Germany.

Reinhard Hohlfeld (R)

Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany/Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

Carmen Infante-Duarte (C)

NeuroCure Clinical Research Center, Department of Neurology and Experimental and Clinical Research Center and Max Delbrück Center for Molecular Medicine, Charité-University Medicine Berlin, Berlin, Germany.

Jan S Kirschke (JS)

Department of Neuroradiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Tania Kümpfel (T)

Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany.

Ralf Linker (R)

Department of Neurology, University Hospital Erlangen, Erlangen, Germany.

Friedemann Paul (F)

NeuroCure Clinical Research Center, Department of Neurology and Experimental and Clinical Research Center and Max Delbrück Center for Molecular Medicine, Charité-University Medicine Berlin, Berlin, Germany.

Steffen Pfeuffer (S)

Department of Neurology, University of Münster, Münster, Germany.

Philipp Sämann (P)

Max Planck Institute of Psychiatry, Munich, Germany.

Gerrit Toenges (G)

Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Frank Weber (F)

Max Planck Institute of Psychiatry, Munich, Germany; Neurological Clinic, Medical Park, Bad Camberg, Germany.

Uwe K Zettl (UK)

Department of Neurology, University of Rostock, Rostock, Germany.

Antje Jahn-Eimermacher (A)

Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany/Darmstadt University of Applied Sciences, Darmstadt, Germany.

Gisela Antony (G)

Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany.

Sergiu Groppa (S)

Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Heinz Wiendl (H)

Department of Neurology, University of Münster, Münster, Germany.

Bernhard Hemmer (B)

Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany/Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

Mark Mühlau (M)

Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany/TUM-NIC Neuroimaging Center, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Carsten Lukas (C)

Department of Radiology and Nuclear Medicine, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.

Ralf Gold (R)

Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.

Christina M Lill (CM)

Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany/Genetic and Molecular Epidemiology Group, Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.

Frauke Zipp (F)

Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

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