A pooled case-control study of the apolipoprotein E (APOE) gene in age-related maculopathy.
Age-related maculopathy (ARM) is a multifactorial disorder known to have a substantial genetic component. The epsilon4 allele of the apolipoprotein E gene (APOE-4) has previously been reported to have a protective effect on ARM risk, while the APOE-2 allele may increase disease risk. This study combined four independent data sets (three US and one European) of Caucasian ARM patients and controls in order to obtain better statistical power to examine the role of APOE in ARM. APOE genotype and allele frequencies were compared for 617 ARM cases and 1260 controls, adjusting for age and sex differences between the two groups via multiple logistic regression. The protective effect of the APOE-4 allele on ARM risk was confirmed (age- and sex-adjusted odds ratio (OR) for APOE-4 carriers 0.54, 95% confidence interval (CI) 0.41-0.70, p < 0.0001). The effect of APOE-4 did not differ significantly between males and females and was observed consistently for both atrophic and neovascular ARM. Evidence for an increased risk of ARM due to the APOE-2 allele was found for men, but not for women (OR for men 1.54, 95% CI 0.97-2.45; OR for women 0.74, 95% CI 0.52-1.06, p = 0.01 for interaction of sex and APOE-2 carrier status). These data confirm that the APOE-4 allele, or an allele in linkage disequilibrium with it, reduces the risk of ARM. They also suggest that the effect of the APOE-2 allele may vary by gender, and that APOE-2 may confer an increased risk only to males.
Schmidt
Silke
S
Center for Human Genetics, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Klaver
Caroline
C
Saunders
Ann
A
Postel
Eric
E
De La Paz
Monica
M
Agarwal
Anita
A
Small
Kent
K
Udar
Nitin
N
Ong
John
J
Chalukya
Meenal
M
Nesburn
Anthony
A
Kenney
Cristina
C
Domurath
Ruth
R
Hogan
Molly
M
Mah
Tammy
T
Conley
Yvette
Y
Ferrell
Robert
R
Weeks
Daniel
D
de Jong
Paulus T V M
PT
van Duijn
Cornelia
C
Haines
Jonathan
J
Pericak-Vance
Margaret
M
Gorin
Michael
M
D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E