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Senior Citizen Health & Medicine
Age-Related Macular Degeneration Risk Increases with
Interaction of Genetics and Lifestyle
 Mutant of CFH gene plus smoking increased risk 8.69
times
January 9, 2007 - The interplay between genetic
predisposition and exposure to modifiable risk factors can multiply the
risk for age-related macular degeneration, according to a report in the
January issue of Archives of Ophthalmology, one of the JAMA/Archives
journals.
Age-related macular degeneration (AMD) can cause
blindness and is known to have both genetic and environmental risk
factors, according to background information in the article. Researchers
have previously found that a mutation in the gene for complement factor
H (CFH) is associated with AMD, 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
AMD.
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“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, Sc.D., O.D., M.P.H., 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 AMD.
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 AMD.
> 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 AMD, 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 AMD 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.”
Editor's Note: This study was supported in part by
grants from the National Institutes of Health.
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