Association between polymorphism of the DNA repair SMUG1 and UNG genes and age-related macular degeneration.

PURPOSE: To investigate the association between the g.4235T>C (rs2337395) polymorphism of the UNG gene and the c.-31A>G (rs3087404) polymorphism of the SMUG1 gene and the risk of age-related macular degeneration (AMD), as well as modulation of this association by some environmental and lifestyle factors. METHODS: Overall, 272 AMD patients and 105 control subjects were enrolled in this study. Both polymorphisms were genotyped by restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP). RESULTS: The C/C genotype of the g.4235T>C polymorphism of the UNG gene was associated with an increased risk of dry AMD (odds ratio, 2.54), whereas the T/T genotype of this polymorphism decreased such risk (odds ratio, 0.41). The presence of the T allele of the g.4235T>C polymorphism and the A allele of the c.-31A>G polymorphism of the SMUG1 gene (odds ratio, 2.17 and 2.18, respectively) was associated with an increased risk of AMD severity, expressed by the comparison of the frequencies of genotypes in the group of patients with wet AMD versus those with dry AMD. Conversely, the C/C genotype of the g.4235T>C polymorphism, the G/G genotype of the c.-31A>G polymorphism, and the C/C-G/G combined genotype of both polymorphisms had a protective effect (odds ratio, 0.48, 0.46, and 0.18; respectively). CONCLUSION: The results obtained suggest the potential role of the g.4235T>C and the c.-31A>G polymorphisms in AMD pathogenesis.

Association between the 25129A > C polymorphism of the nuclear respiratory factor 2 gene and age-related macular degeneration.

PURPOSE: Oxidative stress belongs to the main factors of pathogenesis of age-related macular degeneration, characterized by the damage to the retinal pigment epithelium cells and photoreceptors. Retinal pigment epithelium cells are rich in mitochondria, producing large amount of reactive oxygen species, which are by-products of the activity of the respiratory chain. The distribution in the activity of the chain may be evoked by the release of cytochrome C from the mitochondrion to the cytoplasm. This process may activated by nuclear respiratory factor 2, Nrf2, which is encoded by a highly polymorphic gene. In this study we examined the association between age-related macular degeneration risk and the 25129A > C polymorphism of the gene encoding nuclear respiratory factor 2 (rs12594956). MATERIAL AND METHODS: Genotypes were determined in DNA from peripheral blood lymphocytes of 281 patients with age-related macular degeneration (181 with wet form of the disease and 101 with its dry form), and 105 controls by PCR-restriction fragment length polymorphism. RESULTS: A weak association (OR 1.96; p = 0.023) between the C/C genotype of the 25129A > C polymorphism and the occurrence of age-related macular degeneration was found. A stronger association was observed between dry age-related macular degeneration occurrence and the C/C genotype of the polymorphism (OR 2.23; p = 0.018). The A/C genotype decreased the risk of age-related macular degeneration and its dry form (OR 0.51; p = 0.023 and 0.44; p = 0.018, respectively). Potential risk factors such as age, gender, smoking habit, living environment (rural or urban) and family status of age-related macular degeneration increased the risk of AMD associated with the C/C genotype (OR 2.52; p = 0.012). CONCLUSIONS: The 25129A > C polymorphism of the NRF2 gene may be associated with age-related macular degeneration. mitochondria, reactive oxygen species, gene polymorphism, NRF2 gene, age-related macular degeneration - AMD.

The A Allele of the -576G>A polymorphism of the transferrin gene is associated with the increased risk of age-related macular degeneration in smokers.

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries, and its pathogenesis is underlined by genetic and environmental factors. Oxidative stress is a major environmental risk factor of AMD; namely, AMD is associated with the increased level of reactive oxygen species, which may be produced in reactions catalyzed by iron present in the retina. Therefore, variability of the genes of iron metabolism may be important in the AMD risk. In the present study, we analyzed the association between AMD and the -576G>A polymorphism of the transferrin gene or the 1892C>T polymorphism of the transferrin receptor 2 (TFR2) gene in 278 patients with AMD and 105 controls. The former polymorphism is located in the promoter region of the transferrin gene and may affect the level of its transcription, while the latter is a synonymous mutation in the exon 16, which may affect the efficiency of translation of TFR2 mRNA. Transferrin and TFR2 are important in iron homeostasis. The A allele of the -576A>G polymorphism was significantly associated with the increased risk of AMD in tobacco smokers, whereas the 1892C>T polymorphism did not influence the risk of AMD related to smoking. Moreover, each polymorphism does not influence the risk of AMD associated with age, sex or the family history of the disease. In conclusion, the A allele of the -576A>G polymorphism of the transferrin gene may increase the risk of AMD in smokers.

[Posterior polymorphous dystrophy--changes in corneal morphology in confocal microscopy]. / Dystrofia polimorficzna tylna--zmiany w morfologii rogówki obserwowane z uzyciem mikroskopii konfokalnej.

PURPOSE: To describe the in vivo conocal microscopic findings in posterior polymorphous dystrophy (PPD). MATERIAL AND METHODS: Eleven patients (22 eyes) with PPD suspected or clinically diagnosed were examined using scanning slit white light confocal microscopy (ConfoScan 3, Nidek Technologies). RESULTS: Endothelial cell densities ranged from 716 to 2380 cells/mm2 and endothelial polymegathism was noted in all cases. In 5 cases PPD changes was reported unilateral. Confocal microscopy demonstrated a variety of vesicular and linear abnormalities. In 13 eyes exhibited bright, nucleus-like structures within endothelial cells. Stromal edema was noted in 4 cases. CONCLUSIONS: To our knowledge, we present the largest case series of PPD imaged by in vivo confocal microscopy. Confocal microscopy images of PPD are very characteristic. This method allows to confirm presumptive or to identify final diagnosis. Our study enhances the value of confocal microscopy in detection and monitoring corneal abnormalities.