Apolipoprotein E genotype related differences in brain lesions of multiple sclerosis.
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.
Fazekas
F
F
Department of Neurology, Karl-Franzens University, Graz, Austria. franz.fazekas@kfunigraz.ac.at
Strasser-Fuchs
S
S
Schmidt
H
H
Enzinger
C
C
Ropele
S
S
Lechner
A
A
Flooh
E
E
Schmidt
R
R
Hartung
H P
HP
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
D053327:Apolipoprotein E4; D001057:Apolipoproteins E