New research suggests that one’s genetic make-up interacts with two modifiable risk factors - obesity and smoking - to multiply the risk of developing age-related macular degeneration (AMD), a potentially blinding degenerative eye disorder.

“These new data suggest that the level of risk conferred by these factors (obesity and smoking) depends pretty strongly on a person’s underlying genetic predisposition,” said Dr. Debra A. Schaumberg from Brigham and Women’s Hospital in Boston.

In addition to obesity and smoking, a variation in a gene called complement factor H (CFH) is also known to increase the risk that a person will develop AMD. A mutation in another gene - known as LOC387715 - also raises the risk of AMD.

Schaumberg’s team studied how genes and lifestyle interact to increase the risk of AMD in 457 men and women with AMD and 1,071 “controls,” subjects of the same age without AMD. All of these individuals have been followed regularly since the late 1970s or 1980s as part of either the Nurses’ Health Study or the Health Professionals Follow-Up Study.

According to the report, published in the Archives of Ophthalmology, individuals with one or two copies of the CFH mutation were nearly two-fold and four-fold, respectively, more likely to develop AMD.

Those with one or two copies of the LOC387715 mutation raised the odds of AMD more than two-fold and more than five-fold, respectively.

The proportion of AMD cases attributable to these two gene mutations was 63 percent.

Compared with individuals with two normal copies of each gene, individuals with two copies of the risk mutation in both gene types were 50 times more likely to develop AMD.

This work, Schaumberg said, provides “confirmation…of the importance of these two very common genetic (mutations) in determining a person’s risk of macular degeneration.”

“But these genes alone do not tell the whole story,” she said, noting that cigarette smoking and obesity multiplied the risks associated with these mutations.

For example, obese individuals who carried two copies of the CFH gene mutation were 12-times as likely as non-obese non-carriers to develop AMD. For LOC387715, risk increased more than 6-fold for those with two copies of the gene mutation who did not smoke and more than 22-fold for those with two copies of the mutant gene who did smoke.

“Although the identification of the genetic risk factors is a milestone in our understanding of macular degeneration, we should not forget the importance of the ‘traditional’ risk factors such as smoking and obesity,” Schaumberg said.

“These are the factors that a person can do something about now. Never start smoking, or stop if you already have; eat well to prevent obesity, or lose weight if already obese,” she advised.

SOURCE: Archives of Ophthalmology, January 2007.