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Mult Scler. 2019 Apr;25(5):661-668. doi: 10.1177/1352458518763541. Epub 2018 Mar 13.

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

Author information

1
Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
2
Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany; Department of Neurology, Bern University Hospital, University of Bern, Bern, Switzerland.
3
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.
4
Department of Radiology and Nuclear Medicine, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
5
Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
6
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.
7
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany.
8
Department of Neurology, University of Rostock, Rostock, Germany.
9
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilians University, Munich, Germany/Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
10
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.
11
Department of Neuroradiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
12
Department of Neurology, University Hospital Erlangen, Erlangen, Germany.
13
Department of Neurology, University of Münster, Münster, Germany.
14
Max Planck Institute of Psychiatry, Munich, Germany.
15
Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
16
Max Planck Institute of Psychiatry, Munich, Germany; Neurological Clinic, Medical Park, Bad Camberg, Germany.
17
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.
18
Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany/Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
19
Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
20
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.

Abstract

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.

KEYWORDS:

MRI; Neurodegeneration; SNP; brain atrophy; genetics; gray matter; risk factor; smoking

PMID:
29532745
DOI:
10.1177/1352458518763541

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