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Öğe Association Between Human Leukocyte Antigen Gene Polymorphisms And Multiple Epıya-C Repeats İn Gastrointestinal Disorders(Baishideng Publishing Group Inc, 2020) Demirci, Mehmet; Demiryas, Süleyman; Yılmaz, Erkan; Uysal, Ömer; Kepil, Nuray; ., ve diğer.Background: Polymorphisms of human leukocyte antigen (HLA) genes are suggested to increase the risk of gastric cancer (GC). Aim: To investigate the HLA allele frequencies of patients with GC relative to a control group in terms of CagA+ multiple (? 2) EPIYA-C repeats. Methods: The patient group comprised 94 patients [44 GC and 50 duodenal ulcer (DU) patients], and the control group comprised 86 individuals [(50 non-ulcer dyspepsia patients and 36 people with asymptomatic Helicobacter pylori (H. pylori)]. Polymerase chain reaction was performed for the amplification of the H. pylori cagA gene and typing of EPIYA motifs. HLA sequence-specific oligonucleotide (SSO) typing was performed using Lifecodes SSO typing kits (HLA-A, HLA-B HLA-C, HLA-DRB1, and HLA-DQA1-B1 kits). Results: The comparison of GC cases in terms of CagA+ multiple (? 2) EPIYA-C repeats showed that only the HLA-DQB1*06 allele [odds ratio (OR): 0.37, P = 0.036] was significantly lower, but significance was lost after correction (Pc = 0.1845). The HLA-DQA1*01 allele had a high ratio in GC cases with multiple EPIYA-C repeats, but this was not significant in the univariate analysis. We compared allele frequencies in the DU cases alone and in GC and DU cases together using the same criterion, and none of the HLA alleles were significantly associated with GC or DU. Also, none of the alleles were detected as independent risk factors after the multivariate analysis. On the other hand, in a multivariate logistic regression with no discriminative criterion, HLA-DQA1*01 (OR = 1.848), HLA-DQB1*06 (OR = 1.821) and HLA-A*02 (OR = 1.579) alleles were detected as independent risk factors for GC and DU. Conclusion: None of the HLA alleles were detected as independent risk factors in terms of CagA+ multiple EPIYA-C repeats. However, HLA-DQA1*01, HLA-DQB1*0601, and HLA-A*2 were independent risk factors with no criterion in the multivariate analysis. We suggest that the association of these alleles with gastric malignancies is not specifically related to cagA and multiple EPIYA C repeats.Öğe Association between polymorphisms in HLA-A, HLA-B, HLA-DR, and DQ genes from gastric cancer and duodenal ulcer patients and cagL among cagA-positive Helicobacter pylori strains: The first study in a Turkish population(Elsevier, 2020) Kocak, Banu Tufan; Saribas, Suat; Demiryas, Suleyman; Yilmaz, Erkan; Uysal, Omer; Kepil, Nuray; Demirci, MehmetColonization of the human gastric mucosa by H. pylori may cause peptic and duodenal ulcers (DUs), gastric lymphomas, and gastric cancers. The cagL gene is a component of cag T4SS and is involved in cagA translocation into host. An association between the risk of gastric cancer and the type of HLA class II (DR and/or DQ) was suggested in different populations. The aim of this study was to investigate, the clinical association of the cagL gene with host HLA alleles in H. pylori strains that were isolated from patients with gastric cancer, DU, and non-ulcer dyspepsia (NUD) and to determine the HLA allele that confers susceptibility or resistance for the risk of gastric cancer and DU development in Turkish patients. A total of 94 patients (44 gastric cancer and 50 DU patients; 58 male, 36 female; mean age, 49.6 years), and 86 individuals (50 NUD patients and 36 persons with normal gastrointestinal system [NGIS]; 30 male, 56 female; mean age, 47.3 years) were included as the patient and the control groups, respectively. CagA and cagL were determined by PCR method. DNA from peripheral blood samples was obtained by EZ-DNA extraction kit. For HLA SSO typing, LIFECODES SSO Typing kits (HLA-A, HLA-B HLA-C, HLA-DRB1 and HLA-DQA1/B1 kits) were used. The CagL/CagA positivity distribution in the groups were as follows: 42 (95.4%) gastric cancer, 46 (92%) DU and, 34 (68%) NUD and no NGIS cases. The HLA-DQA1*01 (OR: 3.82) allele was significantly different, suggesting that these individuals with H. pylori strains harbouring the CagL/CagA positivity are susceptible to the risk of gastric cancer and DU, and the HLA-DQA1*05 (OR, 0.318) allele was suggested as a protective allele for the risk of gastric cancer and DU using univariate analyses. HLA-DQA1*01 (OR, 2.21), HLA-DQB1*06 (OR, 2.67), sex (male, OR, 2.27), and CagL/CagA/(< 2) EPIYA C repeats (OR, 5.72) were detected independent risk factors that increased the risk of gastric cancer and DU using multivariate analyses. However, the HLA-DRB1*04 (OR, 0.28) allele was shown to be a protective allele, which decreased the risk of gastric cancer and DU. Gastric pathologies result from an interaction between bacterial virulence factors, host epigenetic and environmental factors, and H. pylori strain heterogeneity, such as genotypic variation among strains and variations in H. pylori populations within an individual host.Öğe Helicobacter pylori-miRNA interaction in gastric cancer tissues: First prospective study from Turkey(Edizioni Int Srl, 2019) Demiryas, Suleyman; Kocazeybek, Bekir; Demirci, Mehmet; Caliskan, Reyhan; Kepil, Nuray; Uysal, Hayriye Kirkoyun; Dinc, Harika OykuHelicobacter pylori (H. pylori) is involved in the etiology of gastric cancer (GC). miRNAs are short RNAs that regulate gene expression by marking mRNAs for degradation. miRNAs are involved in tumorigenesis, metastasis, and cell proliferation. We aimed to investigate the miRNA expression profiles of tissues from H. pylori Wand (-) GC patients. Forty GC patients, 20 H. pylori Wand 20 H. pylori (-), and a healthy control group were included. The miRNA expression levels were investigated by microarrays and quantitative RT-PCR. We detected 9 upregulated and 4 downregulated miRNAs by microarray. We selected 5 upregulated and 5 downregulated miRNAs for the quantitative RT-PCR assay. The relative fold changes of miRNAs in the cancerous tissue and non-tumor mucosa specimens of H. pylori (+) GC patients for hsa-miR-194 were 4.24- and 3.83-fold higher, respectively, whereas the hsa-miR-145 expression levels were downregulated 0.33-fold and 0.43-fold, respectively, in the same group. The presence of H. pylori significantly upregulated hsa-miR-194 and downregulated hsa-miR-145 expression levels in H. pylofi(+)GC cases, compared to H. pylori (-) GC cases. Regional differences in the virulence of H. pylori strains may also be involved in the up- or downregulation of miRNA expression levels.Öğe In-vivo Microwave Dielectric Properties of Healthy and Carcinogenic Rat Nasal Tissues from 500 MHz to 6 GHz(IEEE, 2019) Yilmaz, Tuba; Ozsobaci, Nural Pastaci; Alkan, Falma Ales; Kepil, Nuray; Akduman, IbrahimDielectric properties of rat nasal tissue and nasal carcinoma is given in this work between 500 MHz to 6 GHz. Nasal carcinoma is induced by oral administration of single dose 20 7,12-Dimethylbenz[a]anthracene (DMBA) dissolved in 1 ml olive oil to 47 days old Sprague Dawley (SD) rats. A granular tissue anomaly in one rat along with bleeding is observed after 15 weeks from the administration of the carcinogenic agent. In-vivo dielectric properties are collected both from the granular nasal carcinoma tissue and healthy counterpart with open-ended coaxial probe technique. A median dielectric property discrepancy is observed in the whole frequency range between the nasal carcinoma and healthy tissues.
