The combination of a certain genetic variation, along with inflammatory factors and smoking, significantly increases the risk of the vision disorder age-related macular degeneration, according to a study.//
Age-related macular degeneration (AMD) is the most important cause of irreversible visual loss in the elderly of the Western world, according to background information in the article. Hereditary factors play a role in AMD, and inflammation also may be a factor.
Dominiek D. G. Despriet, M.D., of the Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues assessed the association between the complement factor H (CFH) gene and AMD and investigated the effect of smoking, serum inflammatory markers, and genetic variation of C-reactive protein (CRP). The study included 5,681 individuals age 55 years or older who had the gene mutation CFH Y402H. Information on smoking, CRP serum levels, and other measures were assessed at baseline.
The frequency of CFH Y402H was 36.2 percent. At baseline, there were 2,062 persons (36.3 percent) with any type of AMD (prevalent cases). During an average follow-up of 8 years, 1,649 (35.5 percent) of 4,642 participants progressed to a higher stage of AMD (new cases), including 93 (5.6 percent) who developed late AMD.
The researchers found that that the CFH gene was a major risk factor for AMD. The gene was implicated in all stages of AMD from early hallmarks such as drusen (material that builds up in the retina of the eye) to vision-disabling late AMD and the risks increased with each successive stage to stage 11 for late AMD. Individuals homozygous (having two identical gene alleles at the corresponding site on a chromosome) for the CFH Y402H gene had a 48 percent cumulative risk of developing late AMD by age 95 years while this risk did not exceed 22 percent for noncarriers. Smoking and elevated serum CRP levels further increased the risk.
'These data suggest that CFH Y
402H may be a causal factor in more than 50 percent of all AMD cases in the general population,' the authors write.
'The effect of CFH is significantly influenced by environmental and genetic factors that determine the inflammatory response and activate the complement pathway.'
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