Genetic Association of Apolipoprotein E with Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an important regulator of cholesterol and lipid transport, appears to be associated with neurodegeneration. The apoE gene (APOE) polymorphism is a strong risk factor for various neurodegenerative diseases, and the apoE protein has been demonstrated in disease-associated lesions of these disorders. Hypothesizing that variants of APOE act as a potential risk factor for AMD, we performed a genetic-association study among 88 AMD cases and 901 controls derived from the population-based Rotterdam Study in the Netherlands. The APOE polymorphism showed a significant association with the risk for AMD; the APOE epsilon4 allele was associated with a decreased risk (odds ratio 0.43 [95% confidence interval 0.21-0. 88]), and the epsilon2 allele was associated with a slightly increased risk of AMD (odds ratio 1.5 [95% confidence interval 0.8-2. 82]). To investigate whether apoE is directly involved in the pathogenesis of AMD, we studied apoE immunoreactivity in 15 AMD and 10 control maculae and found that apoE staining was consistently present in the disease-associated deposits in AMD-maculae-that is, drusen and basal laminar deposit. Our results suggest that APOE is a susceptibility gene for AMD.

An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation

“…Interestingly, the E4 allele has been reported by several independent groups as being significantly less prevalent among AMD cases when compared with the corresponding control populations [Klaver et al, 1998a;Souied et al, 1998;Simonelli et al, 2001;Baird et al, 2004;Zareparsi et al, 2004]. The E4 polymorphism is associated with a protective effect against AMD, while the E2 allele is weakly associated with a slightly increased risk for developing late AMD (see our meta-analysis).…”

“…The E4 isoform is also associated with various neurodegenerative diseases, most notably Alzheimer Disease (AD) [Chapman et al, 2001;Laws et al, 2003]. Cardiovascular disease, AD, and AMD share a number of similar pathological features [Klaver et al, 1998a[Klaver et al, ,1999Mullins et al, 2000;Dentchev et al, 2003]. ApoE is also a ubiquitous component of soft drusen, a hallmark of early AMD development [Anderson et al, 2001].…”

“…Investigators have attempted to determine the role of ApoE in AMD development and pathogenesis [Klaver et al, 1998a;Souied et al, 1998;Baird et al, 2004;Zareparsi et al, 2004]. Interestingly, the E4 allele has been reported by several independent groups as being significantly less prevalent among AMD cases when compared with the corresponding control populations [Klaver et al, 1998a;Souied et al, 1998;Simonelli et al, 2001;Baird et al, 2004;Zareparsi et al, 2004].…”

Génétique de la dégénérescence maculaire liée à l’âge

“…C'est aussi une protéine chaperonne importante dans le cytoplasme des cellules. C'était donc un possible gène candidat et deux études respectivement menées par Souied et al et Klaver et al en 1998 ont conclu à son association à la DMLA [7,8]. Dans ces deux études, l'isoforme 4 apparaît comme protectrice, avec des odds ratio respectifs de 0,34 et 0,43.…”

Transport and Retinal Capture of Lutein and Zeaxanthin with Reference to Age-related Macular Degeneration

“…For instance, large amounts of lipids are released from degenerating cell membranes after nerve cell loss, thus stimulating astrocytes to synthesise ApoE, which binds these excess lipids and distributes them appropriately for reuse in cell membrane biosynthesis. 47 This observation prompted Klaver et al to speculate that a high degree of ApoE biosynthesis is required to support the high rate of photoreceptor renewal in the macular region. 47 Indeed, it has been demonstrated that mice, which were fed a high-fat diet, or which were deficient in ApoE, exhibit an increase in the thickness of Bruch's membrane, 62 which is seen in association with ageing and with AMD.…”