Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Macula Degeneration, Age-Related (ARMD4, ARMD7) [H35.3]

OMIM numbers: 610698 (ARMD4), 134370 (CFH), 610149 (ARMD7), 602194 (HTRA1)

Dr. rer. nat. Christoph Marschall, Dipl.-Biol. Christine Schack,
Dipl.-Biol. Christina Sofeso

Scientific Background

Age-related macula degeneration (AMD or ARMD) is a disease of the macula lutea (yellow spot) and is the most common cause of age-related vision loss. It affects approx. 4.5 million people in Germany. There are two types of AMD – dry and wet. Dry macula degeneration (ARMD4) affects approx. 85% of all AMD patients. A decrease in metabolic performance causes deposition of lipids (drusen) under the retina which initially remain asymptomatic. In the course of the disease, cells of the retinal pigment epithelium may die to a large extent, which causes visual impairment. Wet macula degeneration (ARMD7) is characterized by in-growth of blood vessels under the retina causing edema and bleeding. Scarring of the vascular membranes may result in vision loss. Wet AMD is less common than dry AMD and is characterized by a rapid and irreversible course.

A major risk factor for AMD is age. Furthermore, other factors such as smoking, unprotected sun exposure of the eyes as well as familial predisposition play a major role. Currently, various genetic variants that are frequently found in association with one of the seven subtypes of AMD are known. The two most common forms are dry AMD, which is associated with a polymorphism in the complement factor H gene (CFH-Y402H), and wet AMD, which correlates with a polymorphism in the promoter region in the HTRA serine protease 1 gene (HTRA1-512G>A). In the heterozygous state, the CFH-Y402H polymorphism (rs1061170) has been associated with an approx. three to five-fold risk and in the homozygous state with an approx. three to eight-fold risk for dry macula degeneration (ARMD4) and early development of drusen. The HTRA1-512G/A polymorphism (rs11200638) is located in the regulatory promoter region of the HTRA1 gene and is presumed to result in an increased gene expression. In the homozygous state, this polymorphism is assumed to be associated with a 8-fold higher risk for wet macular degeneration (ARMD7).