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.

CKD Increases the Risk of Age-Related Macular Degeneration

“…13,15 Another non-complement-related gene, the APOE 2 allele, has been linked to increased risk of both CKD and AMD, and part of this association may be mediated by its effects on lipid metabolism. 17,18 However, in our study, adjusting for CFHY402H polymorphism, serum lipids, systemic inflammatory markers, hypertension, and diabetes did not attenuate the association between CKD and AMD, suggesting links between the two diseases that are not entirely explained by these factors. We did not adjust for other inflammatory markers, such as C-reactive protein or other complement protein variants associated with CKD.…”

“…15 Second, recent studies suggest that CKD and AMD share several common genetic susceptibility loci, in particular, those related to key complement pathway proteins. [12][13][14][15][16][17][18]20,21 Genetic variants in complement factor H are associated with some forms of kidney disease, such as atypical hemolytic uremic syndrome, 12,14 whereas C3 variants are associated with IgA nephropathy. 16 Both complement factor H and C3 deficiency are associated with type II membranoproliferative glomerulonephritis, 14,20,21 a disease characterized by kidney failure and early onset retinal drusen, which are structurally and compositionally identical to those that occur in AMD.…”

“…11 More recent evidence suggests that the two conditions have common susceptibility genes, such as complement factor H (CFH), [12][13][14] complement C3, 15,16 and apolipoprotein E (APOE). 17,18 Finally, there are a number of rare inherited syndromes that involve both renal and ocular abnormalities. 19 There have been no studies, however, that have examined if the two conditions are associated independently of age and common risk factors.…”

Complex Disease: A new vision for age-related macular degeneration

“…By contrast, with the exception of the increased relative risk associated with the e4 allele of ApoE, 22 the majority of studies of AMD that have focused on the genes that have been associated with juvenile forms of hereditary macular degenerations have accounted for a very small percentage of AMD-affected individuals. 23 The hunt is now on for the rest of the genes that contribute to AMD.…”

Application of Nutrigenomics in Eye Health

“…The apolipoliprotein E4 allele is associated with a 50% reduced risk of AMD [38][39][40][41][42][43]. Recently, three independent teams simultaneously demonstrated a significant association between the Y402H polymorphism of the complement factor H (CFH) gene and AMD in North American subjects [44][45][46], immediately followed by three other corroborating papers in North American populations [47][48][49], one study from France [50] and one from Iceland [51].…”