Three new genes connected with age-related macular degeneration (AMD) have been found in a detailed genetic study.
Two of these genes are involved in the cholesterol pathway.
"Genome-wide association studies require large numbers of patients to discover significant genetic associations. The success of this effort was made possible by a community-wide scientific collaboration of sharing DNA samples and analyzing the genomes of more than 18,000 people," said Dr. Paul A. Sieving.
"This study increases our understanding of DNA variations that predict individual risks of AMD and provides clues for developing effective therapies," he added.
Researchers have previously discovered genes that account for a significant portion of AMD risk through genome-wide association studies (GWAS), which scan the entire DNA of individuals to uncover genetic variations related to certain diseases.
Dr. Anand Swaroop, and Dr. Goncalo Abecasis, professor of biostatistics at the University of Michigan, Ann Arbor,' led the recent large GWAS.
The strongest AMD genetic association found in the study was in a region on chromosome 22, near a gene called metalloproteinase inhibitor 3 (TIMP3).
Mutations in the TIMP3 gene were previously found to cause Sorsby's fundus dystrophy, a rare inherited early-onset form of macular degeneration.
Although further research is needed, it is likely that the genetic region pinpointed influences the expression of TIMP3.
The study has also shed light on a new biological pathway for AMD disease development, by uncovering two genes associated with AMD risk in the high-density lipoprotein (HDL) cholesterol pathway: human hepatic lipase (LIPC) and cholesterol ester transfer protein (CETP).
Scientists identified two additional genes, lipoprotein lipase (LPL) and ATP binding cassette transporter 1 (ABCA1), that may be involved in the cholesterol pathway as well, but more research is needed to confirm these findings.
It is believed that early stages of AMD are affected by accumulation of oxidation products of cholesterol and other lipids in the retinal pigment epithelium, a layer of cells in the back of the eye.
However, the relationship between HDL cholesterol levels in the blood and AMD is still unclear.
"We suspect that these genetic variations found in the cholesterol pathway impact the retina differently from the circulatory system, so cholesterol levels in the blood may not provide meaningful information about AMD risk. Nonetheless, we have uncovered a major biochemical pathway that may be a target for future AMD treatments," explained Swaroop.
Results of this large-scale collaborative study were published in the Proceedings of the National Academy of Sciences.