Neurodegenerative Genes Polymorphisms of the -491A/T APOE, the -877T/C APP and the Risk of Primary Open-angle Glaucoma in the Polish Population.

BACKGROUND: Glaucoma is characterized by optic neuropathy of the retinal ganglion cell. It may be possible that ß-amyloid (Aß) and apolipoprotein E (APOE), the main proteins of the pathogenesis of AD, play a role in glaucoma development. The aim of this study was to evaluate a relationship between the APP and APOE gene polymorphisms and the risk of primary open-angle glaucoma (POAG) occurrence. MATERIALS AND METHODS: The study consisted of 183 patients with POAG and 209 healthy subjects. Genomic DNA was extracted from peripheral blood. Analysis of the gene polymorphisms was performed using PCR-RFLP. RESULTS: We found a statistically significant increase of the -491 T allele frequency (p=0.02; OR=1.48; 95% CI=1.06-2.08) of APOE in POAG compared to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the APP polymorphism between patients and controls group. We also found an association between APOE polymorphic variant and retinal nerve fiber layer (RNFL). There was a statistically significant difference in the APOE gene A/T genotype frequency in the early POAG stage and middle-advanced POAG stage in comparison to the advanced POAG stage (p=0.04; OR=3.38; 95% CI=1.04-10.97). CONCLUSIONS: The -491 T allele of APOE polymorphism may be associated with a risk of POAG occurrence in the Polish population.

Mapping cortical thickness of the patients with unilateral end-stage open angle glaucoma on planar cerebral cortex maps.

PURPOSE: To estimate and compare cerebral cortex thickness in patients with unilateral end-stage glaucoma with that of age-matched individuals with unaffected vision. METHODS: 14 patients with unilateral end-stage primary open angle glaucoma (POAG) and 12 age-matched control individuals with no problems with vision were selected for the study based on detailed ophthalmic examination. For each participant 3D high-resolution structural brain T1-weighted magnetization prepared MR images were acquired on a 3.0 T scanner. Brain cortex thickness was estimated using the FreeSurfer image analysis environment. After warping of subjects' cortical surfaces to FreeSurfer common space, differences between POAG and control groups were inferred at the group analysis level with the General Linear Model. RESULTS: The analysis performed revealed local thinning in the visual cortex areas in the POAG group. Statistically significant differences form 600 mm2 clusters located in the Brodmann area BA19 in the left and right hemisphere. CONCLUSION: Unilateral vision loss due to end-stage neuropathy from POAG is associated with significant thinning of cortical areas employed in vision.

The protective role of the -735C/T and the -1306C/T polymorphisms of the MMP-2 gene in the development of primary open-angle glaucoma.

BACKGROUND: It has been suggested that the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in the degradation of extracellular matrix components, resulting in ocular tissue damage. The -735C/T and -1306C/T polymorphisms recognized in the promoter region of the MMP-2 gene resulting in its expression level were investigated in association with the development of primary open-angle glaucoma (POAG) in a Polish population. METHODS: DNA samples collected from 271 patients with POAG and 281 healthy controls were used in this study. Polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Clinical parameters of the rim area (RA) and retinal neuron fiber layer (RNFL) were also analyzed. RESULTS: We found that the -735C/T and -1306C/T polymorphisms of MMP-2 were not associated with a risk of POAG. However, both the -735T/T (OR = 0.18 (0.04-0.92) p = 0.03) and the -1306T/T (OR = 0.14 (0.03-0.67) p = 0.007) genotypes of MMP-2 were significantly associated with the rim area factor in early stage of POAG suggesting its protective role in the disease progression. CONCLUSION: Finally, our data suggest that gene polymorphisms of MMP-2 may have a protective role in the progression of primary open-angle glaucoma in a Polish population.

BDNF and HSP gene polymorphisms and their influence on the progression of primary open-angle glaucoma in a Polish population.

INTRODUCTION: Glaucoma is a neurodegenerative disease that is often associated with high intraocular pressure (IOP). One of the effects of elevated IOP is disorder of neurotrophic molecules transport, including brain-derived neurotrophic factor (BDNF) and recruit specific cellular proteins called "heat shock proteins" (HSPs). The aim of this study was to evaluate a relationship between the BDNF and HSP70-1 gene polymorphisms with risk occurrence of primary open-angle glaucoma (POAG). MATERIAL AND METHODS: The study consisted of 167 patients with POAG (mean age: 73 ±9) and 193 healthy subjects (mean age: 64 ±13). Genomic DNA was extracted from peripheral blood. Analysis of the gene polymorphisms was performed using PCR-RFLP, using the following restriction enzymes: NlaIII (rs6265) and BsrBI (rs1043618). The Heidelberg retinal tomography (HRT) clinical parameters were also analyzed. The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated. RESULTS: Comparison of the distributions of genotypes and alleles of the 196G/A polymorphism of the BDNF gene as well as 190G/C polymorphism of the HSP70-1 gene and analysis of the odds ratio (OR) showed no statistically significant differences between POAG patients and controls (p > 0.05). However, there was a statistically significant association of the 196G/A of BDNF and 190G/C of HSP70-1 gene polymorphisms with progression of POAG depending on values of clinical parameters. 196G/A of BDNF correlated with the parameters GDx and RA (p = 0.03; p = 0.002, respectively), while 190G/C of HSP70-1 correlated with c/d and RA (p = 0.014, p = 0.024, respectively). CONCLUSIONS: The BDNF 196G/A and HSP70-1 190G/C gene polymorphisms may be related to progression of POAG.

Gene polymorphisms of the MMP1, MMP9, MMP12, IL-1ß and TIMP1 and the risk of primary open-angle glaucoma.

BACKGROUND: Primary open-angle glaucoma (POAG) is the main cause of irreversible blindness worldwide. Matrix metalloproteinases (MMPs) and their regulators (TIMPs and ILs) have been extensively studied as POAG risk factors. Recent reports have showed several single-nucleotide polymorphisms (SNPs) for MMPs, TIMPs and ILs encoding genes in patients with POAG. The aim of this study was to investigate association of the -1607 1G/2G MMP1, -the 1562 C/T MMP9, the -82 A/G MMP12, the -511 C/T IL-1ß and the 372 T/C TIMP1 gene polymorphisms with POAG occurrence and to investigate their impact on main clinical features. MATERIAL AND METHODS: In the present case-control study, we examined group of 511 unrelated Caucasian subjects consist of 255 patients with POAG (mean age 70 ± 15) and 256 controls (mean age 67 ± 16). Determination of genes polymorphic variants was made using polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated. RESULTS: Presented study showed statistically significant increase in the POAG development risk of the -1607 2G/2G MMP1 genotype (OR 1.75; 95% CI, 1.11-2.75; p = 0.014) and for the -1607 2G MMP1 allele (OR 1.35; 95% CI, 1.05-1.73; p = 0.017), as well as for the -1562 C/T MMP9 genotype (OR 1.74; 95% CI, 1.17-2.59; p = 0.006) and the -1562 T MMP9 allele (OR 1.55; 95% CI, 1.10-2.17; p = 0.012) in patients with POAG in comparison with healthy control group. We also observed positive association of the -511 T/T IL-1ß genotype (OR 2.60; 95% CI, 1.41-4.80; p = 0.002) as well as the -511 T IL-1ß allele occurrence with an increased POAG development risk (OR 1.47; 95% CI, 1.13-1.90; p = 0.003). Furthermore, we found an association of the -1607 1G/2G MMP1, -1562 C/T MMP9 (anova, p < 0.001) and the -511 C/T IL-1ß gene polymorphism (anova, p < 0.05) with decreased retinal nerve fibre layer (RNFL) thickness in patients with POAG group. Results displayed also an association of the 372 T/C TIMP1 gene polymorphism with normal range RNFL (anova, p < 0.001). We observed an association of decreased RA value (rim area) with the -82 A/G MMP12 (anova, p < 0.001). Normal RA value was observed in patients with POAG group connected with the 372 T/C TIMP1 (anova, p < 0.05) and the -511 C/T IL-1ß (anova, p < 0.05) genes polymorphisms occurrence. Finally, results showed an association of the -1562 C/T MMP9 (anova, p < 0.001) gene polymorphism with decreased cup/disc index in patients with POAG group. CONCLUSION: In conclusion, we suggest that the -1607 1G/2G MMP1, -1562 C/T MMP9, -511 C/T IL-1ß gene polymorphisms can be considered as an important risk factors associated with POAG.

Association of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326Ser/Cys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of primary open-angle glaucoma.

BACKGROUND: Numerous data have shown that progressive loss of human trabecular meshwork (TM) cells may be connected with oxidative stress. This hypothesis may suggest an association of base excision repair with the risk of primary open angle glaucoma development. PURPOSE: The aim of this study was to evaluate the role of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326SerCys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of POAG. METHODS: Our research included 170 patients with POAG and 193 healthy controls. Gene polymorphisms were investigated by PCR-RFLP. The Heidelberg Retinal Tomography (HRT) clinical parameters were also analyzed. RESULTS: The 399Arg/Gln genotype of the XRCC1 gene was associated with an increased risk for POAG (OR 2.50; 95% CI, 1.54-4.07, P=0.0002). The 399Gln/Gln XRCC1 genotype may increase the risk for POAG progression according to clinical parameters such as cup/disk ratio (c/d) (OR 1.93; 95% CI, 1-3.73, P=0.04) and Rim area (RA factor) (OR 3.88; 95% CI, 1.01-14.82, P=0.04). Moreover, an association was found of retinal nerve-fiber layer (RNFL factor) with the 399Arg/Gln XRCC1 genotype distribution and POAG progression (OR 2.46; 95% CI, 1.06-5.68, P=0.03). In contrast, analysis of the 324Gln/His MUTYH gene polymorphism distribution in the patient group according to RA factor showed that it may reduce the progression of POAG (OR 0.14; 95% CI, 0.02-0.89, P=0.05). Our current study demonstrates an association between the 326Ser/Cys OGG1 gene polymorphism and the 326Cys allele of the OGG1 gene, and progression of POAG. In addition, the presence of the 326His allele of the MUTYH gene may increase the risk for POAG progression, according to the VF parameter (OR 2.57; 95% CI, 1.47-4.57, P=0.0001). CONCLUSION: We suggest that the 399Arg/Gln genotype and the 399Gln allele of the XRCC1 gene may be risk factors for POAG development. Moreover, we postulate that the 399 Arg/Gln XRCC1, the 326 Ser/Cys OGG1 and the 324 Gln/His MUTYH genes polymorphisms may be associated with progression of POAG.

Association of MMP1-1607 1G/2G and TIMP1 372 T/C gene polymorphisms with risk of primary open angle glaucoma in a Polish population.

BACKGROUND: Primary open angle glaucoma (POAG) is considered to be a leading cause of irreversible blindness worldwide. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) have been extensively studied as POAG risk factors. Recently, several single-nucleotide polymorphisms (SNPs) for MMPs and TIMPs encoding genes have been reported in POAG patients. The aim of this study was to investigate association of the -1607 1G/2G MMP1 and 372 T/C TIMP1 gene polymorphisms with risk of POAG in a Polish population. MATERIAL/METHODS: In the present case-control study we examined a group of 449 unrelated Caucasian subjects consisting of 196 POAG patients (66 males and 130 females; mean age 70 ± 14) and 253 controls (72 males and 181 females; mean age 67 ± 16). The MMP1-1607 1G/2G and TIMP1 372 T/C gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated. RESULTS: We found a statistically significant increase of the 2G/2G genotype (OR 1.73; 95% CI 1.05-2.86; p=0.019) as well as the 2G allele frequency (OR 1.34; 95% CI 1.03-1.75; p=0.017) of MMP1 in POAG patients in comparison to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the TIMP1 polymorphism between patients and controls group. We also did not find any association of TIMP1 with MMP1 gene-gene interaction and risk of POAG occurrence. CONCLUSIONS: In conclusion, we suggest that the -1607 1G/2G polymorphism of MMP1 gene may be considered as an important risk factor associated with primary open angle glaucoma in a Polish population. However, further in vivo study is needed to evaluate biological importance of MMPs polymorphisms as a risk factor of POAG.