title: A pooled case-control study of the apolipoprotein E (APOE) gene in age-related maculopathy.
abstract: 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.
authors.affiliation: Center for Human Genetics, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Silke
authors.initials: S
authors.lastname: Schmidt
authors.forename: Caroline
authors.initials: C
authors.lastname: Klaver
authors.forename: Ann
authors.initials: A
authors.lastname: Saunders
authors.forename: Eric
authors.initials: E
authors.lastname: Postel
authors.forename: Monica
authors.initials: M
authors.lastname: De La Paz
authors.forename: Anita
authors.initials: A
authors.lastname: Agarwal
authors.forename: Kent
authors.initials: K
authors.lastname: Small
authors.forename: Nitin
authors.initials: N
authors.lastname: Udar
authors.forename: John
authors.initials: J
authors.lastname: Ong
authors.forename: Meenal
authors.initials: M
authors.lastname: Chalukya
authors.forename: Anthony
authors.initials: A
authors.lastname: Nesburn
authors.forename: Cristina
authors.initials: C
authors.lastname: Kenney
authors.forename: Ruth
authors.initials: R
authors.lastname: Domurath
authors.forename: Molly
authors.initials: M
authors.lastname: Hogan
authors.forename: Tammy
authors.initials: T
authors.lastname: Mah
authors.forename: Yvette
authors.initials: Y
authors.lastname: Conley
authors.forename: Robert
authors.initials: R
authors.lastname: Ferrell
authors.forename: Daniel
authors.initials: D
authors.lastname: Weeks
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Cornelia
authors.initials: C
authors.lastname: van Duijn
authors.forename: Jonathan
authors.initials: J
authors.lastname: Haines
authors.forename: Margaret
authors.initials: M
authors.lastname: Pericak-Vance
authors.forename: Michael
authors.initials: M
authors.lastname: Gorin
mesh_terms: 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
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E