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Genetics and lifestyle interact to increase risk for age-related macular degeneration


The interplay between genetic predisposition and exposure to modifiable risk factors can multiply the risk for age-related macular degeneration.

Age-related macular degeneration ( AMD ) can cause blindness and is known to have both genetic and environmental risk factors.
Researchers have previously found that a mutation in the gene for complement factor H ( CFH ) is associated with age-related macular degeneration, as is a mutation in the gene LOC387715.
Because these mutations are common in the white population, it is likely that other factors, such as obesity and smoking, may modify the risk for age-related macular degeneration. " Elucidation of these modifying factors may increase understanding of disease pathogenesis and suggest lifestyle changes that may prevent AMD or delay the disease onset in carriers of predisposing genetic variants," the authors write.

Debra A. Schaumberg, of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues compared 457 men and women with AMD ( cases ) to 1,071 controls who were the same age and sex as the cases but did not have age-related macular degeneration . All of the individuals were part of either the Nurses' Health Study, a large examination of female registered nurses who were between the ages of 30 and 55 years in 1976, or the Health Professionals Follow-up Study, which includes male U.S. health care professionals who were ages 40 to 75 in 1986.
The participants were examined when they enrolled in the studies and completed a follow-up questionnaire every two years; average age at AMD diagnosis was 68.7 years.

Blood samples were also collected for a genetic analysis. Information about CFH was available for 437 AMD cases and 1,015 controls, while information about LOC387715 was available for 445 AMD cases and 1,041 controls. Compared with those who had two normal copies of each gene ( alleles ), those who had two mutated alleles of both genes were 50 times more likely to develop age-related macular degeneration.

Individuals who carried two mutant alleles of the CFH gene and were not obese were four times as likely as non-obese individuals with two normal alleles to develop AMD. If those individuals also smoked, their risk was 8.69 times as great as non-smoking non-carriers. If individuals were obese and carried two mutant alleles of the CFH gene, their risk increased 12 times as compared with non-obese non-carriers. For LOC387715, risk increased by 6.33 times for those with two mutated alleles who did not smoke and 22.47 times for those with two mutated alleles who did smoke. The genetic risk factors were not affected by other risk factors associated with age-related macular degeneration, including regular aspirin use, fruit intake, fatty acid ratios or alcohol consumption.

Because these genetic mutations are so common, some have questioned the utility of widespread screening for AMD risk, the authors write. " The existence of interactions with modifiable lifestyle factors may provide further impetus for screening individuals who are at potentially greater risk [ for AMD ], for example, cigarette smokers or the obese, " they continue. " Knowledge of the substantial risk of age-related macular degeneration among individuals homozygous for either or both of these major AMD-associated variants might help motivate these individuals to stop smoking, lose weight, modify other risk factors and have regular eye examinations."

Source: Archives of Ophthalmology, 2006


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