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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apolipoproteins E / genetics*
  • Atrophy / genetics
  • Body Mass Index
  • Brain / pathology*
  • Female
  • Genetic Predisposition to Disease / genetics
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / etiology*
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / pathology
  • Polymorphism, Single Nucleotide / genetics
  • Smoking / adverse effects*
  • Young Adult


  • Apolipoproteins E
  • HLA-DRB1 Chains