The apolipoprotein E epsilon4 allele selectively increases the risk of frontotemporal lobar degeneration in males.
OBJECTIVE
To determine whether polymorphic variations in the apolipoprotein E gene (APOE) are associated with increased risk of frontotemporal lobar degeneration (FTLD) when mutation in tau gene is absent.


METHODS
The APOE gene was genotyped by polymerase chain reaction from DNA routinely extracted from blood or brain tissues. The APOE epsilon4 allele frequency in 198 patients with FTLD not associated with mutations in tau gene was compared with that of a control group of 756 normal individuals drawn from the same geographical region. Analyses were done according to clinical subtype or sex.


RESULTS
The APOE epsilon4 allele frequency (19.4%) was increased (p = 0.01) in FTLD v the whole control group (14.1%), while the APOE epsilon2 allele frequency in FTLD (6.5%) was slightly lower than in controls (8.0%) (NS). The APOE epsilon4 allele frequency in men with FTLD (22.3%) was greater (p = 0.002) than in male controls (12.3%); the frequency in women (16.3%) was similar to that in female controls (14.8%) (NS). The APOE epsilon2 allele frequency in men with FTLD was 4.9% while in male controls it was 9.5% (p = 0.06), but there was no difference in women (7.5% v 7.9%, NS). Neither the APOE epsilon2 nor APOE epsilon4 allele frequency varied significantly between any of the clinical subtypes.


CONCLUSIONS
In FTLD not associated with mutations in tau gene, possession of APOE epsilon4 allele in men roughly doubles the chances of developing disease, whereas this has no impact upon disease risk in women.
Srinivasan
R
R
Clinical Neurosciences Research Group, University of Manchester, UK.
Davidson
Y
Y
Gibbons
L
L
Payton
A
A
Richardson
A M T
AM
Varma
A
A
Julien
C
C
Stopford
C
C
Thompson
J
J
Horan
M A
MA
Pendleton
N
N
Pickering-Brown
S M
SM
Neary
D
D
Snowden
J S
JS
Mann
D M A
DM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002531:Cerebellum / Q000378:metabolism; D004252:DNA Mutational Analysis; D003704:Dementia / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D012306:Risk; D012737:Sex Factors; D016875:tau Proteins
D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D016875:tau Proteins