News Release

Sunday, March 5, 2006

Variations in Genes Can Influence the Risk of Developing Age-Related Macular Degeneration and Other Disease Such as Cancer

A team of researchers has determined that variations in certain genes involved in fighting infection can successfully predict the risk of developing age-related macular degeneration (AMD), the leading cause of blindness in white Americans over the age of 60. The team*, led by Bert Gold, Ph.D., and Michael Dean, Ph.D., of the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), identified a genetic variant that is associated with an increased risk of developing AMD. They also found two genetic variants that protect against developing this disease. Study results appear online March 5, 2006 in Nature Genetics**.

The genes analyzed in this study — Complement Factor B (BF) and Complement Component 2 (C2) — contain the instructions to make proteins that activate the body’s immune defense against microbial infections. These defense responses are part of a system called the complement pathways. These pathways involve numerous proteins in the blood that work in association with the body’s immune cells and antibodies to destroy bacteria, viruses or fungi invading the body. Some complement proteins can stimulate inflammation, the redness and swelling that result in tissues when they are infected.

Previous studies have shown that genetic variations in complement pathway genes can cause a dysfunction in the inflammatory response that plays a central role in the pathology of AMD***. Based on these findings, investigators initiated this study, which screened almost 900 patients with AMD and 400 unaffected individuals for genetic variants in the BF and C2 genes. Data analysis revealed that specific variants in each gene were associated with AMD. One genetic variant conferred an increased risk for AMD, while two genetic variants showed protection against developing this disease. These results, when analyzed in association with results linking AMD and genetic variants of Complement Factor H — a gene than contains the instructions to make a protein that inhibits the complement system — showed that 56 percent of the unaffected individuals had a variant that conferred protection to AMD while 74 percent of those with AMD had no protective variants.

“These studies confirm that AMD has a strong genetic component,” said Paul Sieving, M.D., Ph.D., director, National Eye Institute, at NIH. “This may support the development of screening tests for risk of developing AMD, which would allow us to administer treatment early in the course of disease. Knowing the underlying genetic alterations for risk could also aid in developing preventive therapies tailored to an individual’s genetic background.”

AMD is a disease that blurs or destroys sharp, central vision. Approximately 7.3 million Americans have intermediate stages of AMD with a high risk of increasing vision loss, while 1.8 million are visually impaired due to this disease. There is no known cure for AMD.

“We were studying a very common disease, but no one knew its cause. It was unexpected to find that the immune system was involved in causing AMD,” said Gold, Laboratory of Genomic Diversity at NCI and lead author of this study. “Understanding how genetic variations in complement pathway genes are causing this common, complex disease could be very helpful in understanding other complex diseases, such as cancer.”

In the cancer field, there is increasing interest in how infection and chronic inflammation could promote tumor growth. Studies have shown that inflammatory cells can promote tumor growth by producing a favorable growth environment. Complement proteins play an important role in inflammation. This discovery of a link between genetic variants in complement genes and AMD may be relevant to the role of complement in cancer progression.

* Researchers are from the Departments of Ophthalmology and Pathology & Cell Biology, Columbia University, New York, N.Y.; the Department of Ophthalmology and Visual Sciences, Center for Macular Degeneration, University of Iowa, Iowa City, Iowa; Sapio Sciences LLC, York, Pd.; F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pa.; and the Laboratory of Genomic Diversity, NCI, Frederick, Maryland. 

** Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ, Gehrs K, Cramer K, Neel J, Bergeron J, Barile GR, Smith RT, Chang S, Yannuzzi LA, Merriam JC, Barbazetto I, Lerner LE, Russell S, Hoballah J, Hageman J, Stockman H, Hageman GS, Dean M, and Allikmets R. Variation in the Factor B (BF) and Complement Component 2 (C2) genes in the MHC Class III Locus is associated with age-related macular degeneration. Nature Genetics, online March 5, 2006. 

*** Hageman, GS et. al., Common haplotype in the complement regulatory gene, Factor H (HF1/CFH), predisposes Individuals to age-related macular degeneration. Proc. Natl. Acad. Sci. USA, May 17, 2005; 102 (20) 7227-7232.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

NIH…Turning Discovery Into Health®