Analysis of the Expression and Polymorphism ofAPOE, HSP, BDNF,andGRIN2BGenes Associated with the Neurodegeneration Process in the Pathogenesis of Primary Open Angle Glaucoma

Abstract

Glaucoma is characterized by optic neuropathy of the RGC or retinal nerve fiber. The aim of this study was to evaluate a relationship between the neurodegenerative genes' polymorphisms of the APOE (rs449647), BDNF (rs2030324), GRIN2B (rs3764028), and HSP70-1 (rs1043618) and the occurrence risk of POAG and to investigate its effect on allele-specific gene expression. Genomic DNA was extracted from peripheral blood. Analysis of the genes' polymorphisms was performed using PCR-RFLP. The level of mRNA expression was determined by QRT-PCR. We showed a statistically significant association of BDNF and APOE genes' polymorphisms with a risk of POAG occurrence. There was a statistically significant association of the rs2030324 polymorphism with progression of POAG based on cup disc ratio value and rs1043618 polymorphism based on nerve fiber index and rim area. Furthermore, we found that mean HSP70-1 mRNA expression was significantly lower in the case of individuals with the G/G genotype than in the case of minor allele carriers, that is, G/C and C/C. We also found that BDNF and HSP70-1 expression level are associated with the progression of POAG based on rim area value. In conclusion, our results suggest that BDNF, APOE, and HSP70-1 genes might be associated with a risk of POAG occurrence in the Polish population.

Association of Gene Polymorphisms With Primary Open Angle Glaucoma: A Systematic Review and Meta-Analysis

“…Twenty-seven SNPs in 19 genes showed no significant association with POAG in this meta-analysis, including rs1900004 and rs7916697 in the ATOH7 gene, 75,85,102,109,110 rs1001179 in the CAT gene, 61,15 rs1063192, and rs4977756 in the CDKN2B gene, 10,12,67,69,71,75,82,85,102,103,110,157 rs12994401 in the chromosome2p gene, 88,99,101,119,120,125,151 rs1800440 in the CYP1B1 gene, 89,118,158 rs754203 in the CYP46A1 gene, 101,113,124 rs3764028 in the GRIN2B gene, 78,86 -511C/T in the IL-1b gene, 94,135,136 rs3825942, rs1048661, and rs2165241 in the LOXL1 gene, 27,76,80,81,91,93,98,126,[130][131][132] rs1801133 in...…”

“…For SNP rs449647 in the APOE gene, five studies (1937 cases and 1958 controls) were included for calculation. 78,79,138,144,148 Significant association was found in the overall populations in allelic (OR 1.33, 95% CI: 1.13-1.57; P ¼ 0.54, I 2 ¼ 0.00), homozygote (OR 1.61, 95% CI: 1.05-2.45; P ¼ 0.53, I 2 ¼ 0.00), heterozygote (OR 1.32, 95% CI: 1.08-1.62; P ¼ 0.95, I 2 ¼ 0.00), and dominant comparisons (OR 1.37, 95% CI: 1.12-1.66; P ¼ 0.80, I 2 ¼ 0.00), but not in the recessive model ( 65,72,77,82,84,85,115 For SNP rs1799750 in the MMP gene, four studies (885 POAG cases and 875 controls) were involved. 94,95,104,121 The pooled results showed that rs1799750 was significantly correlated with POAG in recessive model (OR 1.64, 95% CI: 1.05-2.56; P ¼ 0.01, I 2 ¼ 73.…”

Exercise as Gene Therapy

“…11,12 Binding to TrkB sets off a series of intracellular signals that promote cell survival, and several studies have concluded that BDNF protects neurons from death and degeneration, both in vitro and in vivo. 13–16 Proposed explanations for BDNF-mediated neuroprotection include maintenance of the cytoskeleton through Rho family GTPases 17 and inhibition of apoptosis through suppression of p53 18 or increased expression of the apoptosis-mediating protein Bcl-2. 19 In addition to its antiapoptotic effects, there is increasing evidence that BDNF may protect neurons through regulation of DNA damage repair (DDR).…”

Brain-derived neurotrophic factor (BDNF) gene polymorphism in a cohort of Egyptian primary open-angle glaucoma (POAG) patients

“…The underlying cause of RGCs death in neurodegenerative diseases seems to be apoptosis; a programmed cell death. Processes that lead to apoptosis in the development of glaucoma include glutamate excite toxicity, blockage of axonal transport, antibodies to heat shock proteins, and ischemia (Nowak et al 2015).…”