Apolipoprotein genotype does not influence MS severity, cognition, or brain atrophy.
BACKGROUND
The influence of APOE allelic heterogeneity on multiple sclerosis (MS) disease severity has been reported in multiple datasets with conflicting results. Several studies have reported an unfavorable association of APOE epsilon4 with more severe clinical disease course while, in contrast, APOE epsilon2 has been associated with a more benign disease course. In this study, we examine the influence of heterogeneity of the APOE gene on disease severity in a large, Australian, population-based MS cohort.


METHODS
Associations between APOE allele status, 2 promoter region single nucleotide polymorphisms (-219 G/T and +113 C/G), and 4 measures of disease severity were tested in 1,006 patients with relapsing-remitting MS and secondary progressive MS: 1) Multiple Sclerosis Severity Score; 2) Progression Index (Expanded Disability Status Scale/disease duration); 3) age at first symptom; and 4) interval between the first and second attack. The Symbol Digit Modalities Test was used as a single cognitive marker in 889 patients. Brain atrophy was measured in 792 patients using the intercaudate ratio. APOE epsilon4 and epsilon3 carriers were stratified by -219 G/T or +113 C/G to investigate haplotypic heterogeneity in the APOE gene region.


RESULTS
In this MS study, neither APOE allele status nor promoter region heterogeneity at positions -219 G/T or +113 C/G influenced the clinical disease severity, cognition, or cerebral atrophy.


CONCLUSIONS
Allelic and haplotypic heterogeneity of the APOE gene region does not influence multiple sclerosis disease course in this well-defined Australian multiple sclerosis cohort.
Royal Melbourne Hospital, Department of Neurology, Parkville, VIC, Australia. Anneke.vanderwalt@mh.org.au
A
A
van der Walt
J
J
Stankovich
M
M
Bahlo
B V
BV
Taylor
I A F
IA
van der Mei
S J
SJ
Foote
T J
TJ
Kilpatrick
J P
JP
Rubio
H
H
Butzkueven
D000328:Adult; D053329:Apolipoprotein E2 / Q000235:genetics; D053318:Apolipoprotein E3 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D001284:Atrophy; D001315:Australia; D001921:Brain / Q000473:pathology*; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D004185:Disability Evaluation; D005260:Female; D006239:Haplotypes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D012720:Severity of Illness Index
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E