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 polymorphisms of the DNA base excision repair genes MUTYH and hOGG1 and age-related macular degeneration.

Age-Related Macular Degeneration (AMD) is an eye disease that results in progressive and irreversible loss of central vision and is considered as the primary cause of visual impairment, including blindness, in the elderly in industrialized countries. Oxidative stress has been implicated in the pathogenesis of AMD. The hOGG1 and the MUTYH genes play an important role in the repair of oxidatively damaged DNA in the base excision repair pathway. The DNA glycosylases encoded by the hOGG1 and MUTYH genes initiate this pathway by recognizing and removing 8-oxoguanine and adenine paired with 8-oxoguanine, respectively. Our study was designed to examine the association between the c.977C>G polymorphism (rs1052133) of the hOGG1 gene and the c.972G>C polymorphism (rs3219489) of the MUTYH gene and AMD as well as the modulation of this association by some clinical and lifestyle factors. Genotypes were determined in DNA from blood of 271 AMD patients, including 101 with wet and 170 with dry form of the disease and 105 sex- and age-matched individuals without AMD. We observed an association between AMD, dry and wet forms of AMD and the C/G genotype and the G allele of the c.977C>G-hOGG1 polymorphism (p 0.006; 0.009; 0.021 and 0.004; 0.005; 0.016 respectively). On the other hand, the C/C genotype and the C allele reduced the risk of AMD as well as of its dry form or wet form (p 0.002; 0.003; 0.010 and 0.004; 0.005; 0.016, respectively). Therefore, the associations we detected were driven by the dry AMD. We observed some statistically significant association between the occurrence of AMD and its dry and wet forms and genotypes of the other polymorphism, the c.972G>C-MUTYH polymorphism, but due to borderline character of all this association we do not consider them as medically relevant. Our findings suggest that the c.977C>G-hOGG1 polymorphism may be associated with dry AMD. Further studies are needed to determine possible association between AMD and the c.972G>C-MUTYH polymorphism.

An association between environmental factors and the IVS4+44C>A polymorphism of the DMT1 gene in age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is an ocular disease affecting macula - the central part of the retina, resulting in the degeneration of photoreceptors and retinal epithelium and causing severe central vision impairment. The pathophysiology of the disease is not completely known, but a significant role is attributed to genetic factors. The contribution of oxidative stress in AMD as a trigger of the degenerative process is well-established. Iron ions may act as a source of reactive oxygen species; therefore, maintaining iron homeostasis is important for redox balance in the organism. Diversity in iron homeostasis genes may counterpart in unbalanced redox state, and thus be involved in AMD pathophysiology. METHODS: In this work, we searched for an association between some single nucleotide polymorphisms in the divalent metal transporter 1 (DMT1) gene intronic IVS4+44C>A (rs224589) and 3'-UTR c.2044T>C (rs2285230) and environmental factors and AMD. Genotyping was performed using the PCR-RFLP method. DNA was obtained from 436 AMD patients and 168 controls. RESULTS: We did not find any association between the genotypes of the two polymorphisms and AMD occurrence. However, we observed that AMD patients living in a rural environment and having the CC genotype of the IVS4+44C>A polymorphism had an increased risk of AMD, while individuals with the CA genotype or the A allele had a decreased risk of the disease. Moreover, in male AMD patients the C allele increased the risk of the disease, while the AA genotype decreased it. CONCLUSIONS: These results suggest that the VS4+44C>A polymorphism of the DMT1 gene may interact with place of living and gender to modulate the risk of AMD.

Lack of association between the c.544G>A polymorphism of the heme oxygenase-2 gene and age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a primary cause of blindness among the elderly in developed countries. The nature of AMD is complex and includes both environmental and hereditary factors. Oxidative stress is thought to be essential in AMD pathogenesis. Iron is suggested to be implicated in the pathogenesis of AMD through the catalysis of the production of reactive oxygen species, which can damage the retina. Heme oxygenase-2 is capable of degradation of heme producing free iron ions, thus, diversity in heme oxygenase-2 gene may contribute to AMD. In the present work we analyzed the association between the c.544G>A polymorphism of the heme oxygenase-2 gene (HMOX2) (rs1051308) and AMD. MATERIAL/METHODS: This study enrolled 276 AMD patients and 105 sex- and age-matched controls. Genotyping of the polymorphism was performed with restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) on DNA isolated from peripheral blood. RESULTS: We did not find any association between the genotypes of the c.544G>A polymorphism and the occurrence of AMD. This lack of association was independent of potential AMD risk factors: tobacco smoking, sex and age. Moreover, we did not find any association between AMD and smoking in our study population. CONCLUSIONS: The results suggest that the c.544G>A polymorphism of the heme oxygenase-2 gene is not associated with AMD in this Polish subpopulation.

DNA damage/repair and polymorphism of the hOGG1 gene in lymphocytes of AMD patients.

Oxidative stress is thought to play a role in the pathogenesis of age-related macular degeneration (AMD). We determined the extent of oxidative DNA damage and the kinetics of its removal as well as the genotypes of the Ser326Cys polymorphism of the hOGG1 gene in lymphocytes of 30 wet AMD patients and 30 controls. Oxidative DNA damage induced by hydrogen peroxide and its repair were evaluated by the comet assay and DNA repair enzymes. We observed a higher extent of endogenous oxidative DNA damage and a lower efficacy of its repair in AMD patients as compared with the controls. We did not find any correlation between the extent of DNA damage and efficacy of DNA repair with genotypes of the Ser326Cys polymorphism. The results obtained suggest that oxidative DNA damage and inefficient DNA repair can be associated with AMD and the variability of the hOOG1 gene may not contribute to this association.

Association between vascular endothelial growth factor gene polymorphisms and age-related macular degeneration in a Polish population.

The pathogenesis of age-related macular degeneration (AMD) is thought to be determined by an array of environmental and genetic factors. The association of increased expression of vascular endothelial growth factor (VEGF) with AMD, especially the wet form of AMD, was reported in several studies. The VEGF gene is highly polymorphic and some of its polymorphisms may affect its expression. In our work, we searched for an association between the -460C> (rs833061) and -634G>C (rs2010963) polymorphisms of the VEGF gene and the occurrence of AMD and its dry and wet forms. We have chosen these polymorphisms because they were shown to be significant in other studies and we previously showed their association with diabetic retinopathy. A total of 401 individuals were enrolled in this study: 136 controls, and 88 patients with dry and 177 with wet AMD. The polymorphisms were determined with DNA from peripheral blood lymphocytes by allele-specific and restriction fragment length polymorphism polymerase chain reaction. The significance of the polymorphisms was assessed by multiple logistic regression, producing odds ratios (ORs) and 95% confidence intervals (CIs). We observed a weak association (OR 2.90) between AMD occurrence and the C/T genotype of the -460C>T polymorphism. An association (OR 3.77) between the C/T genotype of the -460C>T polymorphism and the occurrence of dry AMD was observed. The T/T genotype considerably lowered the risk of dry AMD (OR 0.19). Dry AMD was associated with the C/C genotype of the -634G>C polymorphism (OR 3.68). Another weak association (OR 2.63) was found between the C/T genotype of the -460C>T polymorphism and the occurrence of wet AMD. The occurrence of AMD was correlated with the presence of the combined C/T-G/G genotype of both polymorphisms (OR 2.41), whereas the T/T-G/G and T/T-G/C genotypes exerted a protective effect against the disease (OR 0.22 and 0.48, respectively). The presence of the C/T-G/G and C/T-C/C combined genotypes increased the risk of dry AMD (OR 2.08 and 3.77, respectively), whereas the presence of the T/T-G/G and T/T-G/C genotypes decreased the risk (OR 0.15 and 0.28, respectively). In the wet form of AMD, the combined genotype C/T-G/G slightly favored the disease (OR 2.61) and the T/T-G/G genotype had a protective effect (OR 0.25). Analysis of haplotypes of both polymorphisms yielded similar results for AMD in general as well as for the dry and wet forms of the disease: the CG haplotype favored both forms of AMD, whereas the TG haplotype protected against both forms of AMD. The results obtained indicate that the -460C>T and -634G>C polymorphisms of the VEGF gene may be associated with the dry and wet forms of AMD in a Polish population.

[Genetic aspects of age-related macular degeneration]. / Aspekty genetyczne zwyrodnienia plamki zwiazanego z wiekiem.

Age-related macular degeneration (AMD) is a progressive disease characterized in macula photoreceptors degeneration that leads to loss of central vision in elderly people, especially in developed countries. Many environmental and genetic factors have influence on the occurrence and progression of AMD as well as its form: either dry or exudative. Despite of the extensive research, etiology and molecular background of AMD are poorly understood. Due to advanced biochemical and biophysical techniques some clinical aspects of AMD have been described in details, however, the genetic basis of AMD is still under investigation. The results of some research indicate that the genes, which products may play a role in the pathogenesis of AMD could be CFB, C2, CFHR1, CFHR3, C3, ABCR, APOE, CCL2, CFH, CX3CR1, ERCC6, FSCN2, HMCN1, HTRA1, LOC387715, PLEKHA1, TIMP3 and VEGF-A. The variability of these genes, expressed by their polymorphisms, may also contribute to thye occurrence and progression of AMD. Studying of genetic aspects of AMD many bring results playing a role in the prevention, diagnostics and treatment of this disease.

Distribution of the C-460T polymorphism of the vascular endothelial growth factor gene in age-related macular degeneration.

PURPOSE: To assess the association between genotypes and alleles of the C-460T polymorphism of the vascular endothelial growth factor (VEGF) gene and the risk of wet form of age-related macular degeneration (AMD). MATERIALS AND METHODS: 100 patients with clinically diagnosed wet form of AMD and 104 healthy individuals were enrolled in this study. The patients were diagnosed by optical coherence tomography, fluorescein angiography and indocyanin green angiography. The allele-specific polymerase chain reaction was used to determine the genotypes of the C-460T polymorphism of the VEGF gene. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a logistic regression model to assess the assoctiation betweeen genotypes of the C-460T polymorphism and AMD occurrence. RESULTS: A difference was observed in the genotype distributions between patients and controls. An association (OR 3.04, 95% CI 1.65-5.60) was found between wet form of AMD and the C/T genotype. On the other hand, the T/T genotype displayed the protective effect against the disease. CONCLUSION: The C-460T polymorphism of the endothelial growth factor can be considered as a potential marker for the wet form of age-related macular degeneration.

[Intraoperative choroidal hemorrhage in patient with Osler-Rendu syndrome]. / Sródoperacyjny krwotok naczyniówkowy u pacjenta z zespollem rendu--Oslera.

UNLABELLED: The authors describe a 79-year-old man with Osler-Rendu-Weber syndrome, who developed intraoperative choroidal hemorrhage in left eye. During phacoemulsification under local anesthesia, shallowing of the anterior chamber was observed. Acetazolamide was administered and peribulbar block performed. Phacoemulsification was continued and intraocular lens implanted. Five months postoperatively resolution of the choroidal hemorrhage was observed. Best corrected visual acuity was 0.5. Patient developed retinal embolism in his right eye 16 years earlier. CONCLUSIONS: (1) Choroidal hemorrhage may occur more commonly in patients with Osler-Rendu-Weber syndrome. Recognition of this possible association and institution of appropriate intraoperative precautions may facilitate a good visual outcome. (2) Paradoxical embolization (stroke, retinal embolism) is the most serious consequence of hereditary hemorrhagic telangiectasia.

[The use of antibiotics during the perioperative period and incidence of complications--based on data from selected ocular surgery centers in Poland]. / Stosowanie antybiotyków w okresie okolooperacyjnym a wystepowanie powiklan--na podstawie danych z wybranych osrodków okulistycznych w Polsce.

The aim of the study was to evaluate effectiveness of prophylactic antibiotics usage and the prevalence of infectious complications, after ocular surgery. Authors analyzed data from 53 ocular surgery centers in Poland: 28674 cases of cataract surgery, 6518 cases of complicated cataract surgery, 1387 cases of contemporary cataract and glaucoma surgery and 2978 cases of glaucoma surgery. The prevalence of endophthalmitis in this group of patients ranged from 0.29% after cataract surgery to 0.93% after complex surgery (cataract and glaucoma), and was higher than other studies show. This is because the study group was much smaller. The study is the first step to create optimal schema of antibiotics usage during ocular surgery. Rational antibiotics usage is very important because of worldwide growing antibiotic resistance.