Purchase this article with an account.
G. J. McKay, AMD APOE Consortia; Pooled Data Analysis of Apoe Risk in AMD. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1274.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Previous reports have provided conflicting evidence of association for variation within APOE and AMD. We assessed the impact of APOE on AMD in a pooled data analysis and tested for interaction with age, gender and smoking status.
Univariate analysis was significant with GA for APOE2 (OR=1.21; CI:1.06-1.38; P=0.006) and APOE4 (OR=0.60; CI:0.52-0.69; P=3.14x10-13) with only APOE4 significant for NV AMD (OR=0.69; CI: 0.63-0.75; P=1.59x10-18). Following adjustment for age, gender, centre and smoking, a dominant protective effect was determined for APOE4 (GA OR=0.67; CI:0.57-0.80; P=1.12x10-5; NV OR=0.76; CI: 0.68-0.86; P=6.94x10-6) and an APOE2 susceptibility effect behaved additively (GA OR=1.21; CI: 1.03-1.43; P=0.02). rs405509 improved discrimination of this locus specifically through APOE2, but not APOE4. Gender (OR=1.29 CI:1.18-1.42; P=1.1x10-7), smoking status (ever smoker versus never smoker; OR=1.53; CI:1.38-1.68; P=1.9x10-17) and age (OR=1.08; CI: 1.07-1.09; P=1.1x10-129) were significantly associated with late AMD. There was no evidence to support interaction between APOE haplotype and either gender or smoking status. Heterogeneity (Chi2 = 44.81; df = 2; P<0.00001) was found between smoking status and AMD sub-phenotype; smoking was least associated with early AMD (OR=1.04; CI:0.94-1.16) and most associated with NV (OR=1.58; CI: 1.42-1.76) while its association with GA was intermediate OR=1.37 (CI: 1.18-1.59). APOE4 is significantly less frequent with increasing age particularly in the homozygous state. APOE3 frequency significantly increases with advancing years to the detriment of APOE4.
Our results confirm a role for APOE in AMD aetiology with genotyping at rs405509 offering further discriminative value at this locus. AMD risk significantly increases in females and the effect of smoking was most pronounced in NV AMD. Previous association of APOE with longevity are supported here with APOE4 individuals less likely to live longer. This, in combination with variation in haplotype frequency across different populations, may influence associations from small independent studies.
This PDF is available to Subscribers Only