title: Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis.
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.
authors.affiliation: Department of Neurology, Karl-Franzens University, Graz, Austria. franz.fazekas@kfunigraz.ac.at
authors.forename: F
authors.initials: F
authors.lastname: Fazekas
authors.forename: S
authors.initials: S
authors.lastname: Strasser-Fuchs
authors.forename: H
authors.initials: H
authors.lastname: Kollegger
authors.forename: T
authors.initials: T
authors.lastname: Berger
authors.forename: W
authors.initials: W
authors.lastname: Kristoferitsch
authors.forename: H
authors.initials: H
authors.lastname: Schmidt
authors.forename: C
authors.initials: C
authors.lastname: Enzinger
authors.forename: M
authors.initials: M
authors.lastname: Schiefermeier
authors.forename: C
authors.initials: C
authors.lastname: Schwarz
authors.forename: B
authors.initials: B
authors.lastname: Kornek
authors.forename: M
authors.initials: M
authors.lastname: Reindl
authors.forename: K
authors.initials: K
authors.lastname: Huber
authors.forename: R
authors.initials: R
authors.lastname: Grass
authors.forename: G
authors.initials: G
authors.lastname: Wimmer
authors.forename: K
authors.initials: K
authors.lastname: Vass
authors.forename: K H
authors.initials: KH
authors.lastname: Pfeiffer
authors.forename: H P
authors.initials: HP
authors.lastname: Hartung
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005819:Genetic Markers