An association between polymorphism of the heme oxygenase-1 and -2 genes and age-related macular degeneration

• Published in: Molecular biology reports 2012-03, Vol.39 (3), p.2081-2087
• Main Authors: Synowiec, Ewelina, Szaflik, Jerzy, Chmielewska, Marta, Wozniak, Katarzyna, Sklodowska, Anna, Waszczyk, Maja, Dorecka, Mariola, Blasiak, Janusz, Szaflik, Jacek Pawel
• Format: Article
• Language: English
• Subjects: Age; Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; Environmental factors; Gene polymorphism; Genes; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Genotype; Heme oxygenase (decyclizing); Heme Oxygenase (Decyclizing) - genetics; Heme Oxygenase-1 - genetics; Heme oxygenase-2; Histology; Humans; Iron; Life Sciences; Logistic Models; Macular degeneration; Macular Degeneration - genetics; Macular Degeneration - physiopathology; Morphology; Odds Ratio; Oxidative stress; Poland; Polymerase Chain Reaction; Polymorphism; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide - genetics; Restriction fragment length polymorphism; Transversion
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-011-0955-3

Iron may be implicated in the generation of oxidative stress by the catalyzing the Haber–Weiss or Fenton reaction. On the other hand, 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 heme oxygenase-2 (HO-2), encoded by the HMOX2 gene are important markers of iron-related oxidative stress and its consequences. Therefore, variability of the HMOX1 and HMOX2 genes might be implicated in the pathogenesis of AMD through the modulation of the cellular reaction to oxidative stress. In the present work, we investigated the association between AMD and a G → C transversion at the 19 position in the HMOX1 gene (the 19G>C- HMOX1 polymorphism, rs2071747) and a A → G transition at the −42 + 1444 position in the HMOX2 gene (the −42 + 1444A>G- HMOX2 polymorphism, rs2270363) and its modulation by some environmental factors. 279 patients with AMD and 105 controls were recruited in this study and the polymorphisms were typed by restriction fragment length polymorphism and allele-specific polymerase chain reaction (PCR). We observed an association between the occurrence of dry AMD and the G/A genotype of the −42 + 1444A>G- HMOX2 polymorphism (odds ratio (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 the G allele of the −42 + 1444A>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 + 1444A>G- HMOX2 polymorphism protected against AMD progression (OR 0.19, 0.19, 0.34, 0.59, respectively). Therefore, the 19G>C- HMOX1 and the −42 + 1444A>G- HMOX2 polymorphisms may be associated with the occurrence and progression of AMD.