Browsing by Author "Orenay-Boyacioglu, S"
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Item GSTP1 Gene Methylation Profiles in Helicobacter pylori (+) and (-) Antral Intestinal Metaplasia and Distal Gastric Tumour Patients in Turkish PopulationAsik-Sen, G; Kasap, E; Orenay-Boyacioglu, S; Korkmaz, M; Kahraman, E; Unsal, B; Yüksel-Saritas, E; Yuceyar, HBackground/Aims: Gastric cancer (GC) is the second most common malignancy worldwide, with a high mortality rate. The incidence of GC has declined in the western countries during the last decades. The glutathione S-transferases comprise a group of enzymes that are critical in the detoxification of carcinogens. In this study we aimed at the relationship GSTP-1 methylation in patients with intestinal metaplasia with and without Helicobacter pylori infection, gastric cancer and controls. Methodology: The methylation status of GSTP1 gene was analyzed by methylation specific PCR after bisulfate modification in H. pylori (+) (n=25) and (-) (n=25) intestinal metaplasia (IM) patients, GC (n=25) and control subjects (n=15) between September 2009 to November 2011. Results: During the study period 90 patients who underwent endoscopic examination were included in the study. When we considered the GSTP1 gene methylation profile in all of the groups; 26 (28%) patients had methylated GSTP1 gene, 31 (34%) patients had unmethylated GSTP1 gene and 33 (36%) patients had heterogeneously methylated GSTP1 gene. Conclusions: GSTP1 gene methylation profile is not appropriate for early diagnosis of cases with gastric cancer.Item Evidence of associations between brain-derived neurotrophic factor (BDNF) serum levels and gene polymorphisms with tinnitusCoskunoglu, A; Orenay-Boyacioglu, S; Deveci, A; Bayam, M; Onur, E; Onan, A; Cam, FSBackground: Brain-derived neurotrophic factor (BDNF) gene polymorphisms are associated with abnormalities in regulation of BDNF secretion. Studies also linked BDNF polymorphisms with changes in brainstem auditory-evoked response test results. Furthermore, BDNF levels are reduced in tinnitus, psychiatric disorders, depression, dysthymic disorder that may be associated with stress, conversion disorder, and suicide attempts due to crises of life. For this purpose, we investigated whether there is any role of BDNF changes in the pathophysiology of tinnitus. Materials and Methods: In this study, we examined the possible effects of BDNF variants in individuals diagnosed with tinnitus for more than 3 months. Fifty-two tinnitus subjects between the ages of 18 and 55, and 42 years healthy control subjects in the same age group, who were free of any otorhinolaryngology and systemic disease, were selected for examination. The intensity of tinnitus and depression was measured using the tinnitus handicap inventory, and the differential diagnosis of psychiatric diagnoses made using the Structured Clinical Interview for Fourth Edition of Mental Disorders. BDNF gene polymorphism was analyzed in the genomic deoxyribonucleic acid (DNA) samples extracted from the venous blood, and the serum levels of BDNF were measured. One-way analysis of variance and Chi-squared tests were applied. Results: Serum BDNF level was found lower in the tinnitus patients than controls, and it appeared that there is no correlation between BDNF gene polymorphism and tinnitus. Conclusions: This study suggests neurotrophic factors such as BDNF may have a role in tinnitus etiology. Future studies with larger sample size may be required to further confirm our results.Item Boron intake, osteocalcin polymorphism and serum level in postmenopausal osteoporosisBoyacioglu, O; Orenay-Boyacioglu, S; Yildirim, H; Korkmaz, MThe relationship between daily boron intake and osteocalcin-mediated osteoporosis was studied in boron-exposed postmenopausal women. It is known that boron and osteocalcin are important in bone metabolism, however the effect of boron in bone metabolism has not been fully discovered. The study was performed on 53 postmenopausal women aged 55-60 living in parts of Balikesir, Turkey, where the subjects are naturally exposed to high (>= 1 mg/L) or low (< 1 mg/L) boron concentration in drinking water. 24-h urine samples were collected from all participants and creatinine clearance was detected. Boron intake levels of the subjects whose clearance levels were between 80-124 mL/min were measured by inductively coupled plasma-optical emission spectrometry (ICP-OES) in urine samples. Serum osteocalcin levels of the subjects were measured by osteocalcin enzyme-linked immunosorbent assay (ELISA) kit. Osteocalcin polymorphism rs1800247 was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serum osteocalcin levels in boron-exposed postmenopausal women were significantly higher than that of control group (P <= 0.05) and the correlation between the serum osteocalcin level and rs1800247 polymorphism was not significant in both groups (P > 0.05). The differences in the distribution of osteocalcin genotypes and alleles in postmenopausal women were not significant between the boron exposed and the control groups (P > 0.05). Serum osteocalcin level in the CC genotype was significantly higher compared to the TC genotype in boron-exposed group (P <= 0.05). Our study suggests that daily boron intake of 1 mg/L may affect bone metabolism in postmenopausal women positively.Item Relationship Between Chronic Tinnitus and Glial Cell Line-Derived Neurotrophic Factor Gene rs3812047, rs1110149, and rs884344 Polymorphisms in a Turkish PopulationOrenay-Boyacioglu, S; Coskunoglu, A; Caki, Z; Cam, FSGlial cell line-derived neurotrophic factor (GDNF) plays a key role in early development of central auditory pathway and the inner ear. However, the auditory pathway studies of GDNF gene polymorphisms are scarce in the literature, and the studies especially associated with tinnitus are limited. Our study aimed to identify whether GDNF gene polymorphisms play any roles in the pathophysiology of tinnitus by investigating the relationship between tinnitus and GDNF polymorphisms. A total of 52 patients with chronic tinnitus and ages ranging from 18 to 55 were admitted to the Ear-Nose-Throat outpatient clinic of Celal Bayar University Medical Faculty Hospital of Manisa, Turkey and constituted the study group. Another 42 patients of the same age range, without tinnitus symptoms and lacking any systemic disease, were also admitted to the clinic and formed the control group. The tympanometric, audiological, and psychoacoustic assessments of the subjects were performed. Deoxyribonucleic acid samples obtained using venous blood taken for routine inspections were used to investigate GDNF gene polymorphisms (rs884344, rs3812047, and rs1110149) by polymerase chain reaction-based restriction fragment length polymorphism method. No correlation could be detected between GDNF rs884344 and rs3812047 polymorphisms and subjects with tinnitus (p > 0.05). Heterozygosity was significantly lower for GDNF rs1110149 polymorphism in tinnitus subjects compared to the controls (p < 0.05). However, the allele frequencies for all 3 polymorphisms were not significantly different between tinnitus and control groups (p > 0.05). Failure to detect correlations between tinnitus and GDNF gene polymorphisms suggests this may be due to the fact that the GDNF gene has a variable expression pattern in different tissues and pathologies. Therefore, the study should be improved and its scope should be expanded by including a larger group of patients and different tissues to investigate the expression pattern of GDNF.Item ASSOCIATION OF INTERLEUKIN 12B RS3212227 POLYMORPHISM WITH GASTRIC CANCER, INTESTINAL METAPLASIA, AND Helicobacter pylori INFECTIONOrenay-Boyacioglu, S; Kasap, E; Yuceyar, H; Korkmaz, MInterleukin 12 (IL-12) has a key function in promoting Th1 immune response in the gastrointestinal mucosa. Although cytokine gene polymorphisms are associated with increased risk of gastric cancer (GC), studies on different geographic regions and ethnic groups are not able to draw a consistent result. The current case-control study aims to find out an association between a functional IL-12B rs3212227 polymorphism and the susceptibility and clinical features of the study groups, which are GC, Helicobacter pylori-infected and H. pylori-uninfected intestinal metaplasia (IM). In this study, IL-12B rs3212227 polymorphism was genotyped in 35 GC cases, 25 H. pylori-infected IM patients, 25 H. pylori-uninfected IM patients, and 25 control subjects. PCR-RFLP analysis was performed to find out and compare the polymorphism profiles of case biopsies. There was statistical significance in genotype distributions and allelic frequencies in GC patients with proximal arrest in stomach (p=0.042). The rs3212227 genotypes and allelic frequencies were not correlated with any of the study groups (p>0.05). Other clinical features examined in the GC patients were also not correlated with the rs3212227 genotypes and allelic frequencies (p>0.05). Current findings suggest that IL-12B rs3212227 polymorphism may play a role in GC development.Item Overexpressions of RHOA, CSNK1A1, DVL2, FZD8, and LRP5 genes enhance gastric cancer development in the presence of Helicobacter pyloriDemirci, U; Orenay-Boyacioglu, S; Kasap, E; Gerçeker, E; Bilgiç, F; Yüceyar, H; Yildirim, H; Baykan, AR; Ellidokuz, EB; Korkmaz, MBackground and study aims: Intestinal metaplasia (IM), and Helicobacter pylori (HP) infection can be shown as risk factors in the development of gastric cancer (GC). WNT signaling pathway plays a critical role in carcinogenesis. However, the literature studies are limited on the significance of this pathway for the transition from IM to GC. Patients and methods: We aimed to investigate the importance of the genes of WNT signaling pathways diagnostic and prognostic markers in the presence and absence of HP in conversion from IM to GC. 104 patients, (GC group n = 35, IM group n = 45, control group n = 25) were included in this case-control study. Expression of genes in WNT signalling were searched in study groups with qRT-PCR array and qRT-PCR method. Data were analysed using PCR array data analysis software. Results: Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in the GC and IM groups compared to the control group (p < 0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was observed in patients with metastatic GC compared to patients with GC without metastasis (p < 0.05). It was found that the RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes were statistically significantly over-expressed in diffuse GC patients compared to non-diffuse GC patients (p < 0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in HP positive IM patients compared to HP negative IM patients (p < 0.05). Conclusion: Overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes in IM may suggest that these genes are important markers in the development of IM and inflammation with HP. In addition, these genes are linked to tumor burden in the GC group. Consequently, we can conclude that these genes are poor prognosis biomarkers for GC and have the potential to be used as markers for future treatment monitoring.Item Expression profiles of histone modification genes in gastric cancer progressionOrenay-Boyacioglu, S; Kasap, E; Gerceker, E; Yuceyar, H; Demirci, U; Bilgic, F; Korkmaz, MGastric cancer (GC) development can be attributed to several risk factors including atrophic gastritis (AG), intestinal metaplasia (IM), and the presence of Helicobacter pylori (HP). Also, histone modification is an epigenetic mechanism that plays a pivotal role in GC carcinogenesis. In this preliminary study, we aimed to describe the expression profiles of histone modification in the AG, IM, and GC patient groups. A total of 80 patients with AG (n = 27), IM (n = 25), and GC (n = 28) with an additional 20 control subjects were included in the study. Expression profiles of three histone phosphorylation genes (PAK1, NEK6, and AURKA) and five histone deacetylation genes (HDACs 1, 2, 3, 5, and 7) were examined based on the results of Real Time qPCR method. It was observed that AURKA and HDAC2 genes were significantly overexpressed in all groups compared to the control (P < 0.05). In GC patients, overexpression of HDAC2 gene was detected in the absence of metastasis, and overexpression of AURKA, HDAC2, and NEK6 genes was detected in the presence of metastasis. When cancer involvements were compared, significant overexpression of the HDAC2 gene was noted in overall and corpus involvements (P < 0.05). In addition, overexpression of AURKA, NEK6, HDAC1, and HDAC2 genes and underexpression of HDAC5 gene were detected in the antrum involvement (P < 0.05). In conclusion, decreased expression of HDAC5 in GC is reported for the first time in this study, while supporting the existing literature in AURKA, NEK6, HDAC1, and HDAC2 up regulations during GC development.Item Chronic tinnitus and BDNF/GDNF CpG promoter methylations: a case-control studyOrenay-Boyacioglu, S; Caliskan, M; Boyacioglu, O; Coskunoglu, A; Bozkurt, G; Cam, FSBrain-derived neurotrophic factor (BDNF) and Glial-derived neurotrophic factor (GDNF) are neurotrophic factors that play key roles in the auditory pathway. While the relationship between serum levels and polymorphisms of BDNF/GDNF and chronic tinnitus is emphasized in the literature, there is no study showing the link between the promoter methylations of these genes and tinnitus. For this purpose, the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations was investigated to identify their role in the pathophysiology of tinnitus. In this case-control study, we examined the possible effects of BDNF/GDNF methylations in the blood samples of patients with tinnitus complaints for more than 3months. Sixty tinnitus subjects between the ages of 18-55 and 50 healthy control subjects in the same age group who were free of any otorhinolaryngology and systemic disease were selected for examination. Methylation of total 12 CpG sites in BDNF and GDNF promoter regions were determined by the bisulfite-pyrosequencing method. Statistically significant differences were detected between BDNF CpG6 and GDNF CpG3-5-6 methylation ratios in the comparison of control group and the chronic tinnitus patients (P=0.002, 0.0005, 0.00003, and 0.0029, respectively). To our knowledge, this is the first study in the literature investigating the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations. It is believed that the current results might be supported by investigating the relationships between BDNF/GDNF methylations and genotypes in future research using higher sample sizes.Item Autozygosity in a Turkish family with scoliosis, blindness, and arachnodactyly syndromeOrenay-Boyacioglu, S; Tekin, M; Dundar, MBACKGROUND AND OBJECTIVES: Blindness-scoliosis-arachnodactyly syndrome has been described in a family with parental consanguinity. We present the strategy employed to determine the gene locus responsible for the syndrome. DESIGN AND SETTING: A retrospective study of blindness-scoliosis-arachnodactyly syndrome patients at the Department of Medical Genetics, Erciyes University, between 2009-2010. PATIENTS AND METHODS: Whole genome single nucleotide polymorphisms (SNPs) were scanned using a 250K Affymetrix array. We visually evaluated runs of homozygosity shared by two affected brothers that segregated in the entire pedigree with different combinations due to the unclear affected status of some siblings. Two and multiple-point LOD (logarithm [base 10] of odds) score analyses were performed by easyLINKAGEplus v5.08. RESULTS: Five homozygous blocks over 2 Mb shared by two affected brothers segregated with phenotype in two affected and three unaffected siblings and in the mother whose phenotypes were unequivocal. The longest homozygous block in this analysis was on chromosome 14 between 67817621bp (rs7148416) and 82508151bp (rs17117757). When another sister with positive eye findings was added to the analysis, this region was narrowed to between 67817621bp (rs7148416) and 75657598bp (rs11626830), with a maximum LOD score of 2.3956 by two-point analysis. Three candidate genes were detected in this region. CONCLUSION: This study contributes to the existing literature on the region 67817621 bp 82508151 bp (rs17117757) on chromosome 14 and the three candidate genes, which could be responsible for the syndrome.