Haddad Stephen, Chen Clara A, Santangelo Susan L, Seddon Johanna M
Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, 02114, USA.
Surv Ophthalmol. 2006 Jul-Aug;51(4):316-63. doi: 10.1016/j.survophthal.2006.05.001.
Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness among older adults in the USA and throughout the developed world. Etiological research suggests that AMD is a complex disease, caused by the actions and interactions of multiple genes and environmental factors. Familial aggregation studies, twin studies, and segregation analyses have provided strong evidence for the heritability of AMD, and linkage and association studies have been conducted to localize the disease-causing genes. Whole genome linkage scans have implicated nearly every chromosome in the human genome, with the most replicated signals residing on 1q25-31 and 10q26. Association studies have identified a major risk variant within the complement factor H gene (CFH), and recent reports suggest that PLEKHA1/LOC387715 and the BF/C2 regions may be major risk loci for AMD as well. Several other genes have had at least one positive association finding and deserve further exploration. Among these, apolipoprotein E (APOE) may be a minor risk locus. Additional genes will likely be identified, and future studies should explore the potential interactions of these genes with other genes as well as environmental factors.
年龄相关性黄斑变性（AMD）是美国及整个发达国家老年人视力丧失和失明的主要原因。病因学研究表明，AMD是一种复杂疾病，由多种基因和环境因素的作用及相互作用引起。家族聚集性研究、双生子研究和分离分析为AMD的遗传性提供了有力证据，并且已经开展了连锁和关联研究来定位致病基因。全基因组连锁扫描几乎涉及人类基因组中的每一条染色体，其中最具重复性的信号位于1q25 - 31和10q26。关联研究已经在补体因子H基因（CFH）内鉴定出一个主要风险变异，并且最近的报告表明PLEKHA1/LOC387715和BF/C2区域可能也是AMD的主要风险位点。其他几个基因至少有一项阳性关联发现，值得进一步探索。其中，载脂蛋白E（APOE）可能是一个次要风险位点。可能会鉴定出更多基因，未来的研究应该探索这些基因与其他基因以及环境因素之间的潜在相互作用。
