AGE-RELATED MACULAR DEGENERATION AND LIFESTYLE

Age-related macular degeneration (AMD) has a strong genetic basis, but a healthy lifestyle including a high consumption of anti-oxidants and avoiding tobacco can cancel most of the genetic disposition for the condition, said Caroline Klaver MD PhD, Erasmus Medical Centre, Rotterdam, the Netherlands.

The principal genes associated with AMD are the CFH and ARMS2 genes. In the Rotterdam Eye Study, among patients with early AMD (stage two and three) over three fourths had at least one CFH or ARMS2 risk alleles, eight per cent had three risk alleles and one per cent were double homozygotes, Dr Klaver noted.

Among patients with late, stage 4 AMD, 93 per cent had at least one risk allele, a third had two, 22 per cent had three, and two per cent were double homozygotes, she said. Among patients aged 80 or over with no AMD, 35 per cent had no risk alleles, 46 per cent had one, 15 per cent had two, four per cent had three and none were double homozygotes, she added.

Furthermore, even in the absence of the CFH or ARMS2 risk alleles, patients still had a five per cent risk of developing late AMD by the age of 85 years, she noted. The risk went up to 16 per cent with one risk allele, up to 32 per cent with two risk alleles, and up to 70 per cent with three or four risk alleles.

Both the CFH and the ARMS2 variants are risk factors for both dry and wet AMD, she said. However, the CFH variant has a stronger effect on dry AMD, whereas the ARMS2 variant has a stronger effect on wet AMD, she said.

The protein associated with the CFH gene is an inhibitor of the alternative pathway of the complement system, Dr Klaver said. The current theory is that the risk variant performs the inhibition less effectively, with the over-activation of complement as a result, she explained.

The pathologic mechanism behind the ARMS2 variant is less clear. The gene is located in the mitochondria, which are important for oxidation; therefore it may be that the risk variant interferes with the normal oxidation.

The findings of the Rotterdam Eye Study show that smoking status has a modifying effect on any genetic predisposition to AMD. For example, among non-smokers who were homozygous for the CFH variant, the risk of AMD was 12.51 times higher than in patients without any CFH allele, but among smokers homozygous for the gene the risk was 34 times higher than in patients without any CFH allele. Homozygous former smokers fell around halfway between the two with a 20-fold higher risk.

The effect of diet was even more striking. That is, among those carrying the CFH and/or ARMS2 genetic variants, but who consumed high amounts of zinc, beta carotenes, omega fatty acids or lutein, the rate of AMD was close to that of patients with no genetic risk factors.

“So it appears you can eat away your genetic risk for AMD,†Dr Klaver added.