Klaver C C, Kliffen M, van Duijn C M, Hofman A, Cruts M, Grobbee D E, van Broeckhoven C, de Jong P T
Department of Epidemiology, Erasmus University Medical School, Rotterdam, The Netherlands.
Am J Hum Genet. 1998 Jul;63(1):200-6. doi: 10.1086/301901.
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.
年龄相关性黄斑变性（AMD）是导致失明的最常见老年眼部疾病，其特征是眼部黄斑区神经上皮的退化。载脂蛋白E（apoE）是中枢神经系统的主要载脂蛋白以及胆固醇和脂质转运的重要调节因子，似乎与神经退行性变有关。apoE基因（APOE）多态性是各种神经退行性疾病的一个强大风险因素，并且apoE蛋白已在这些疾病的疾病相关病变中得到证实。假设APOE变体是AMD的一个潜在风险因素，我们在来自荷兰基于人群的鹿特丹研究的88例AMD病例和901例对照中进行了一项基因关联研究。APOE多态性与AMD风险显示出显著关联；APOE ε4等位基因与风险降低相关（优势比0.43 [95%置信区间0.21 - 0.88]），而ε2等位基因与AMD风险略有增加相关（优势比1.5 [95%置信区间0.8 - 2.82]）。为了研究apoE是否直接参与AMD的发病机制，我们研究了15个AMD黄斑和10个对照黄斑中的apoE免疫反应性，发现apoE染色始终存在于AMD黄斑中与疾病相关的沉积物中，即玻璃膜疣和基底膜沉积物中。我们的结果表明APOE是AMD的一个易感基因。
