DNA Repair Based Therapy in Oncology and Neurodegeneration

WOS: 000378333000015

POTENTIAL PROTECTIVE ROLE OF SDF-1 AND CXCR4 GENE VARIANTS IN THE DEVELOPMENT OF DEMENTIA

Background: The aim of this study was to evaluate the role of polymorphisms of stromal cell-derived factor-1 (SDF-1) and chemokine receptor-4 (CXCR4) genes in dementia susceptibility in a Turkish population. Subjects and methods: The study group included 61 dementia patients, while the control group comprised 82 healthy individuals. Gene polymorphisms of SDF-1 3’A G801A (rs1801157) and CXCR4 C138T (rs2228014) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: A significantly reduced risk for developing dementia was found for the group bearing an A allele for SDF-1 3’A polymorphism (p=0.009; x2=6.812; OR=0.626; 95%CI= 0.429-0.913). The frequency of the CXCR4 TT and TC genotype was significantly lower in patients with dementia compared to controls (p=0.028; x2=5.583; OR=0.215; 95%CI=0.05-0.914); (p=0.027; x2=4.919; OR=0.484; 95% CI= 0.246-0.955). Additionally, combined genotype analysis showed that the frequency of SDF1 GACXCR4 CC was significantly lower in patients with dementia in comparison with those of controls (p=0.049; OR=0.560; 95% CI= 0.307±1.020). Conclusions: Our study provides new evidence that SDF1 A and CXCR4 T alleles may be associated with a decreased dementia risk. The present study is important because to our knowledge, it is the first one to be conducted in a Turkish population to date, but we believe that more patients and controls are needed to obtain statistically significant results

The Effect of GHR/exon-3 Polymorphism and Serum GH, IGF-1 and IGFBP-3 Levels in Diabetes and Coronary Heart Disease

Aim: The present study investigated the effects of growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and GH-receptor (GHR)/exon-3 polymorphism on diabetes mellitus (DM) and coronary heart disease (CHD) patients. Patients and Methods: Ninety patients with CHD, 90 patients with DM and 96 controls were included in this study. The GH, IGF-1 and IGFBP-3 serum levels were measured with enzyme-linked immunosorbent assay. GHR/exon-3 variants were determined by multiplex-polymerase chain reaction. Results: The frequency of all alleles and genotypes in all study groups were distributed according to the Hardy-Weinberg equilibrium. In addition, any association between GHR/exon-3 variants and the presence of risk factors were detected. The blood levels of GH, IGF-1 and IGFBP-3 were not distributed according to GHR/exon-3 variants. However, in the DM group, higher levels of IGF-1 and lower levels of GH and IGFBP-3, and in CHD group lower levels of IGF-1, GH and IGFBP-3 were observed. The order of GH levels were DM<CHD< Controls; IGF-1 levels were CHD<Controls<DM and IGFBP-3 levels were CHD<DM<Controls. Conclusion: No direct effect of GHR/exon-3 polymorphism was observed in DM or CHD patients. However GH, IGF-1, IGFBP-3 and insulin were thought to act together to establish body homeostasis in patients with DM and CHD

MMP2 Gene Polymorphisms and MMP2 mRNA Levels in Patients with Superficial Varices of Lower Extremities

Background: Although superficial varices of lower extremities with high morbidity are common, their etiology has not been elucidated yet. Previously, it was thought that venous hypertension was responsible for such cases by causing valvular insufficiency, but recent findings indicate that the changes in the venous wall structure might be main initiating factors. Matrix metalloproteinase enzyme-2 (MMP2) is one of the enzymes known to have functions in remodelling of the extracellular matrix mainly in vascular structures. Materials and Methods: We studied two functional gene polymorphisms in -735 and -1306 regions of matrix metalloproteinase enzyme-2 (MMP2) gene, and their effects on mRNA expression of MMP2. We used a previously defined (PCR-RFLP) method for polymorphism analyses. Results: CC genotype and C allele for MMP2 -735 gene region were more common in the control group and there was no significant difference between groups for MMP2 -1306 gene polymorphisms. MMP2 mRNA levels were higher in the group that had both varices and coronary artery disease (CAD). Conclusion: There was no significant effect of MMP2 polymorphisms on mRNA expression. As MMP2 mRNA levels were higher in varices patients with CAD compared to the CAD only and varices only groups. it is necessary to make advanced researches to elucidate the relationship between CAD and varices

Role of Caspase-9 Gene Ex5+32 G > A (rs1052576) Variant in Susceptibility to Primary Brain Tumors

Background/Aim: This study is the first to evaluate the relationship of caspase-9 (CASP-9) gene polymorphism with the risk for primary brain tumor development. Materials and Methods: The study group included 43 glioma and 27 meningioma patients and 76 healthy individuals. CASP-9 gene Ex5+32 G>A (rs1052576) polymorphism was analyzed by real-time polymerase chain reaction (RT-PCR). Results: Individuals with the CASP-9 GG genotype had significantly decreased risk of developing a glioma brain tumor (p=0.024). Additionally, the GA genotype was significantly lower in patients with glioma than the control group (p=0.019). A significantly decreased risk of developing glioma was found in the A allele carrier group (p=0.024). However, there was no statistically significant relationship between CASP-9 polymorphism and brain meningioma (p=0.493). Conclusion: CASP-9 (rs1052576) mutant A allele seems to be a protective factor for glioma brain tumor. Future studies with a larger sample size will clarify the possible roles of CASP-9 gene in the etiology and progression of primary brain tumors

Expression of miR-373 and its predicted target genes E-cadherin and CD44 in patients with laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma (LSCC) is a genomically complex disease that is difficult to target, and efforts have been made to identify new treatment strategies and molecular markers that might stratify patients and individualize options for treatment. miR-373 has diametrically opposed roles in different stages and types of cancers. miR-373 has been suggested to quantitatively control E-cadherin and CD44 expression. We studied the expression of miR-373, E-cadherin and CD44 in laryngeal squamous cell carcinoma and evaluated the association between the disease and clinical characteristics of patients. Tumor tissues were collected from 24 laryngeal cancer patients. Adjacent normal tissue samples were also obtained as controls. After RNA isolation, we assessed the miR-373, E-cadherin and CD44 levels. As endogenous controls, we used the small RNA U6 and GAPDH TaqMan (R) to normalize the levels of expression of miR-373, E-cadherin and CD44. The fold change in the expression of the genes in larynx tumor and control tissues was calculated using the 2-(Delta Delta CT) method. miR-373 was significantly upregulated in seventeen tumor samples compared to controls. However, the expression levels of both E-cadherin and CD44 mRNA were found to be significantly downregulated in tumor versus control regions (p=0.026 and p=0.005, respectively). We did not find any significant difference in the expression levels of miR-373, E-cadherin or CD44 and cancer risk factors. miR-373, E-cadherin and CD44 may be involved in the etiopathogenesis of laryngeal cancer. It can be suggested that E-cadherin and CD44 are functional targets of miR-373, but we need further studies to investigate this hypothesis