title: Apolipoprotein E genotype related differences in brain lesions of multiple sclerosis.
abstract: OBJECTIVE
  Clinical reports have speculated on a more severe course of multiple sclerosis in patients with the apolipoprotein E (apoE) epsilon4 allele. As this could be reflected by differences in the severity of tissue damage MRI was used to obtain further support for a disease modifying effect of the apoE genotype.
  
  
  METHODS
  Brain MR scans of 83 patients (mean age 35.5 (SD 9.5 years) who participated in a cross sectional study on the distribution of genotype patterns in multiple sclerosis. The total lesion load on proton density weighted (T2-LL) and T1 weighted scans (T1-LL) obtained with conventional spin echo sequences at 1.5 T was measured. A "black hole" ratio ((T1-LL/T2-LL)x100) was also calculated. This indicates the proportion of multiple sclerosis lesions with more severe tissue damage and may reflect disease aggressiveness or quality of repair.
  
  
  RESULTS
  Patients with the apoE-epsilon3/epsilon4 genotype (n=19) showed a non-significantly greater T2-LL (16.0 (SD 14.0) cm(3)) than patients with the epsilon2/epsilon3 (n=11; 13.3 (9.5) cm(3)) or the epsilon3/epsilon3 genotype (n=49; 9.4 (SD 9.2) cm(3)). Both the T1-LL (2.6 (SD 3.3) v 1.6 (SD 2.4) and 1.2 (SD 3.0) cm(3); p=0.04) and the black hole ratio (14.3 SD 11.9) v 7.4 (SD 9.3) and 8.4 (SD 13.3)%; p=0.02), however, were significantly higher in epsilon3/epsilon4 patients. Similar differences were seen when comparing patients with at least one epsilon4 allele with the remainder of the group.
  
  
  CONCLUSIONS
  These data support speculations on a modulation of multiple sclerosis severity by the apoE genotype which can be attributed to more extensive tissue destruction or less efficient repair in carriers of the epsilon4 allele.
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: Schmidt
authors.forename: C
authors.initials: C
authors.lastname: Enzinger
authors.forename: S
authors.initials: S
authors.lastname: Ropele
authors.forename: A
authors.initials: A
authors.lastname: Lechner
authors.forename: E
authors.initials: E
authors.lastname: Flooh
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
authors.forename: H P
authors.initials: HP
authors.lastname: Hartung
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E