Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis

Neurology. 2001 Sep 11;57(5):853-7. doi: 10.1212/wnl.57.5.853.

Abstract

Objective: The apolipoprotein E (APOE) polymorphism is known to impact on various neurologic disorders and has differential effects on the immune system and on CNS repair. Previous findings concerning a possible modulation of the clinical course of MS have been inconsistent, however.

Methods: In a cross-sectional study, the authors investigated 374 patients with clinically definite MS and a disease duration of at least 3 years and related their clinical and demographic findings to the allelic polymorphism of the APOE gene. The genotype distribution of patients with MS was compared with a cohort of 389 asymptomatic, randomly selected elderly volunteers.

Results: The authors found no significant differences in the distribution of genotypes between patients with MS and controls. However, patients with MS with the epsilon4 allele (n = 85) had a significantly higher progression index of disability (0.46 +/- 0.4 versus 0.33 +/- 0.26; p < 0.004) and a worse ranked MS severity score (5.1 +/- 1.9 versus 5.7 +/- 1.7; p = 0.05) than their non-epsilon4 counterparts, despite significantly more frequent long-term immunotherapy in epsilon4 carriers (74% versus 58%; p < 0.007). The annual relapse rate in epsilon4 carriers (0.87 +/- 0.56) was significantly higher than in patients with MS without an epsilon4 allele (0.71 +/- 0.47; p = 0.03).

Conclusions: These results suggest no effect of the APOE genotype on susceptibility to MS, but indicate an association of the APOE epsilon4 allele with a more severe course of the disease.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Chi-Square Distribution
  • Cohort Studies
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Genetic Markers / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / genetics*

Substances

  • Apolipoprotein E4
  • Apolipoproteins E
  • Genetic Markers