Souied E, Kaplan J, Coscas G, Soubrane G
Clinique Ophtalmologique Universitaire de Créteil, Université Paris XII, 40, avenue de Verdun, 94010 Créteil, France.
J Fr Ophtalmol. 2001 Oct;24(8):875-85.
Age related macular degeneration (AMD) is the main cause of blindness after age 55 in western countries. These last past years, several lines of evidence such as familial aggregation or twin studies suggested a genetic component in AMD. However, the late onset of the disease and the fact that AMD is a polygenic and multifactorial disease are the main limiting factors for linkage studies. Gene candidate strategy allowed the exclusion of several genes (VMD2, RDS, TIMP3) and lead to the implication of two genetic factors: the apoE gene (involved in the transport of lipids) and the ABCR gene (involved in Stargardt macular dystrophy). Concerning the apoE gene, a lower frequency of the epsilon 4 alleles carriers was observed in the exudative AMD population compared with controls, supporting the idea of a role of the apoE gene in exudative AMD with drusen. These results, together with ultrastructural studies, suggest that allele epsilon 4 is a protective factor for drusen and thus for AMD. For the ABCR gene, several studies and a large multicentric study definitively show that some heterozygous mutations are predisposing factors for AMD, in a polygenic and multifactorial model.
年龄相关性黄斑变性（AMD）是西方国家55岁以后失明的主要原因。在过去几年中，家族聚集性或双胞胎研究等一系列证据表明AMD存在遗传因素。然而，该疾病的迟发性以及AMD是一种多基因和多因素疾病这一事实，是连锁研究的主要限制因素。候选基因策略排除了几个基因（VMD2、RDS、TIMP3），并发现了两个遗传因素：载脂蛋白E基因（参与脂质运输）和ABCR基因（参与Stargardt黄斑营养不良）。关于载脂蛋白E基因，与对照组相比，在渗出性AMD人群中观察到ε4等位基因携带者的频率较低，这支持了载脂蛋白E基因在伴有玻璃膜疣的渗出性AMD中起作用的观点。这些结果与超微结构研究一起表明，ε4等位基因是玻璃膜疣以及AMD的保护因素。对于ABCR基因，多项研究和一项大型多中心研究明确表明，在多基因和多因素模型中，一些杂合突变是AMD的易感因素。
