Abstract
Purpose: :
Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD) and heme oxygenase-1 (HO-1, encoded by the HMOX1 gene) and the closely related heme oxygenase-2 (HO-2, encoded by the HMOX2 gene) are important markers of oxidative stress and its consequences. Therefore, genetic variability of HO-1 and HO-2 might modulate the reaction to oxidative stress and in this way be implicated in the pathogenesis of AMD. In the present work, we investigated the association between AMD and a G → C transversion at 19 in the HMOX1 gene (the 19G>C-HMOX1 polymorphism, rs2071747) and a A → G transition at -42 + 1444 in the HMOX2 gene (the -42+1444 A>G-HMOX2 polymorphism, rs2270363) and its modulation by some environmental factors.
Methods: :
279 patients with AMD and 105 controls were recruited in the study and the polymorphisms were typed by restriction fragment length polymorphism and allele-specific PCR.
Results: :
We observed an association between dry AMD and the G/A genotype of the -42+1444 A>G-HMOX2 polymorphism (OR 2.72), whereas the G/G genotype reduced the risk of dry AMD (OR 0.41). The G/C genotype and the C allele of the 19 G>C-HMOX1 polymorphism and the G/G genotype and G allele of the -2+1444 A>G-HMOX2 polymorphism were associated with progression of AMD from dry to wet form (OR 4.83, 5.20, 2.55, 1.69, respectively). On the other hand, the G/G genotype and the G allele of the 19 G>C-HMOX1 polymorphism and the A/G genotype and the A allele of the 42+1444 A>G-HMOX2 polymorphism protected against AMD progression (OR 0.19, 0.19, 0.34, 0.59, respectively).
Conclusions: :
The 19 G>C-HMOX1 and the 42+1444A>G -HMOX2 polymorphisms may be associated with the occurrence and progression of AMD.
Keywords: age-related macular degeneration • genetics