title: APOE genotype is a major predictor of long-term progression of disability in MS.
abstract: OBJECTIVE
  The authors recently reported that the APOE epsilon4 allele is associated with significantly greater progression of disability in a 2-year follow-up of patients with MS. In this study, these findings are substantiated and extended in a much larger group of patients followed for up to 40 years.
  
  
  METHODS
  Two hundred five patients with clinically definite MS who were genotyped for the APOE epsilon4 carrier state were included. Groups of patients with (n = 41) and without (n = 164) APOE epsilon4 alleles were compared for latency to expanded disability status scale (EDSS) scores of 4.0 and 6.0 by Kaplan-Meier analysis with the log rank test. The results were adjusted for age at onset and sex by Cox regression analysis.
  
  
  RESULTS
  The APOE epsilon4 allele frequency in patients with MS (0.10) was similar to that in the general Israeli population. There was a significant effect of APOE genotype on the latency to reach EDSS 4.0 and 6.0 (p = 0.0002 and p = 0.0006 by two-tailed log rank test). Median latencies were shorter by 12 and 11 years in the APOE epsilon4 group for these outcomes. These results were significant after adjustment for age at onset and sex.
  
  
  CONCLUSIONS
  The APOE epsilon4 allele is associated with significantly faster progression of disability in MS. This is the first genetic factor to be identified with a major impact on the progression of disability in this disease.
authors.affiliation: Department of Neurology, Sackler Faculty of Medicine, Tel Aviv Medical Center, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Chapman
authors.forename: S
authors.initials: S
authors.lastname: Vinokurov
authors.forename: A
authors.initials: A
authors.lastname: Achiron
authors.forename: D M
authors.initials: DM
authors.lastname: Karussis
authors.forename: K
authors.initials: K
authors.lastname: Mitosek-Szewczyk
authors.forename: M
authors.initials: M
authors.lastname: Birnbaum
authors.forename: D M
authors.initials: DM
authors.lastname: Michaelson
authors.forename: A D
authors.initials: AD
authors.lastname: Korczyn
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E