Our data demonstrated that ApoE 4/2 genotype was less frequently observed in old patients (65 years and more) with exudative AMD compared to old healthy controls.
The APOE isoform ε2 is a risk factor for age-related macular degeneration; nevertheless, APOE absence in humans and mice does not significantly affect the retina.
Cholesterol efflux genes (APOE and ABCA1) were identified as risk factors for AMD, although how cholesterol efflux influences accumulation of this lipid in sub-RPE deposits remains elusive.
Stratification analysis by ethnicity revealed that the ApoE ε4 carriers was associated with neovascular AMD in both Caucasians (OR = 0.62, 95% CI = 0.47-0.83) and East Asians (OR = 0.68, 95% CI = 0.58-0.79).
The current study was conducted to investigate the association of Apolipoprotein E (ApoE) polymorphism with the treatment response to ranibizumab for exudative AMD.
The aim of this study was to determine the potential association between 10 single nucleotide polymorphisms (SNPs) located in 4 different genetic regions (CFI, COL8A1, LIPC, and APOE), and choroidal neovascularization in age-related macular degeneration and the development of choroidal neovascularization in highly myopic eyes of a Caucasian population.
Here, we propose that ApoE serves a fundamentally different purpose in regulating cholesterol homeostasis in the retinal pigment epithelium and this could explain why allelic risk factors are flipped for AMD compared to Alzheimer's disease.
A logistic model for early AMD found a significant association with AD diagnosis (p < 0.0001), after adjusting for confounders (age, smoking, hypertension, high and low density lipoproteins, cataract surgery and APOE ε4 carrier status).
However, there have been no reports on gene expression patterns in animal models of non-neovascular AMD with abnormal lipid metabolism such as apolipoprotein E knockout and human apolipoprotein E2 transgenic mice.
In conclusion, our study did not confirm the impact of rs2075650 on advanced AMD risk, indicating that rs2075650 is unlikely a superior marker for APOE/TOMM40 susceptible region with advanced AMD in Han Chinese population.
The individual effects on the risk of AMD for 18 of the 19 SNPs were in a consistent direction with those previously reported, including a protective effect of the APOE ε4 allele.
Our study shows that pathogenic subretinal inflammation is APOE isoform-dependent and provides the rationale for the previously unexplained implication of the APOE2 isoform as a risk factor and the APOE4 isoform as a protective factor in AMD pathogenesis.
A spectrum of complement dysregulation was modeled on the APOE4AMD mouse model by crossing these mice to complement factor H knockout (cfh-/-) mice to test the impact of excess complement activation, and by crossing them to soluble-complement-receptor-1-related protein y (sCrry) mice, in which sCrry acts as a potent inhibitor of mouse complement acting in a manner similar to CFH.
A total of 24 variants from five genes (BCMO1, BCO2, NPCL1L1, ABCG8, and FADS2) not previously related to AMD and four genes related to AMD in previous studies (SCARB1, ABCA1, APOE, and ALDH3A2) were associated independently with AMD, after adjusting for age and ancestry.
To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes.
GWAS meta-analysis confirmed previously reported association of variants at the complement factor H (CFH) (peak P = 1.5×10(-31)) and age-related maculopathy susceptibility 2 (ARMS2) (P = 4.3×10(-24)) loci, and suggested Apolipoprotein E (ApoE) polymorphisms (rs2075650; P = 1.1×10(-6)) associated with early AMD.
The CD subtype of AMD was significantly associated with current smoking as well as variants in the complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), complement factor B/complement component 2 (CFB/C2), complement component 3 (C3), and apolipoprotein E (APOE) genes.
The genetics of AMD began initially with the appreciation of familial aggregation and increase risk and expanded with the initial association of APOE variants with the disease.
Consistent with a pathogenic role for Aβ, we show here that a mouse model of AMD that invokes multiple factors that are known to modify AMD risk (aged human apolipoprotein E 4 targeted replacement mice on a high-fat, cholesterol-enriched diet) presents with Aβ-containing deposits basal to the retinal pigmented epithelium (RPE), histopathologic changes in the RPE, and a deficit in scotopic electroretinographic response, which is reflective of impaired visual function.