Browsing by Author "Yaman, Derya"

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Evaluation of silent information regulator T (SIRT) 1 and Forkhead Box O (FOXO) transcription factor 1 and 3a genes in glaucoma
(2020) Yaman, Derya; Takmaz, Tamer; Yuksel, Nilay; Dincer, Selin Akad; Sahin, Feride Iffet; 0000-0001-7308-9673; 0000-0002-3808-7004; 33200312; AAK-2511-2021; AAC-7232-2020
Analysis of the reactive oxygen species (ROS)-detoxifying biomarkers may elucidate the mitochondrial dysfunction in glaucoma pathogenesis. Therefore, we purposed to investigate the effects of ROS-detoxifying molecules including Silent Information Regulator T1 (SIRT1) and Forkhead Box O 1 (FOXO1) and 3a (FOXO3a) transcription factors in patients with glaucoma. Our analyses included 20 eyes from patients with primary open-angle glaucoma (POAG) and 20 eyes from patients with pseudoexfoliation glaucoma (PXG) who were scheduled for trabeculectomy. After extraction of total RNA from trabecular meshwork tissue, we compared the levels of SIRT1, FOXO1and FOXO3a genes in the oxidative pathway with the level of glyceraldehyde-3 phosphate dehydrogenase (GAPDH), the reference gene, using real-time polymerase chain reaction. Relative gene expression was calculated using the threshold cycle (2(-Delta Delta CT)) method. We observed similarly reduced expression levels of SIRT1, FOXO1, and FOXO3a genes versus GAPDH among patient groups (p = 0.40; p = 0.56; p = 0.35, respectively). This is the first study to identify the role of SIRT1 and FOXOs in human TM with glaucoma. Relative expression levels of SIRT1, FOXO1, and FOXO3a genes versus a control gene (GAPDH) were decreased in POAG and PXG groups. Our results show that SIRT1and FOXOs (1-3a) deserve special attention in the pathogenesis of glaucoma.
Frequency of IL-1B Gene Polymorphisms in Patients with Gastroesophageal Cancer in the Hakkari Region
(2023) Yaman, Derya; Akad Dincer, Selin; Karaka, Yusuf; Unsoy, Gozde; Terzi, Yunus Kasim; Sahin, Feride Iffet
Objective: Gastric cancer is a complex malignant tumor associated with chronic inflammation. In the present study, we aimed to investigate the frequency of interleukin 18 (IL-18) gene polymorphisms affecting gene expression in patients with gastroesophageal cancer (GC) diagnosed in the Hakkari region. Methods: Blood samples of 17 patients with GC (group 1) and 59 healthy controls (group 2) were enrolled in the study. The single-nucleotide polymorphisms (SNPs) rs1143627 c.-118C>T, rs16944 c.-598C>T, and rs1143634 c.315C>T polymorphisms in the IL-18 gene were studied among groups via polymerase chain reaction and restriction fragment length polymorphism. Results were analyzed by descriptive statistics and the x(2) test. The association between SNPs and GC risk was evaluated by odd ratios (ORs) and 95% confidence intervals. Results: The frequencies of the three genotypes in the SNP rs1143627, rs16944, and rs1143634 were similar between the groups, and C>T transition was not found to be significant [(p=0.69, OR: 1.16 95%, confidence interval (CI): 0.54-2.51; p= 0.16, OR: 0.58 95%, CI: 0.26-1.25; p=0.7, OR: 0.83 95%, CI: 0.32-2.11, respectively]. Conclusion: Our results did not reveal any significant association between IL-18 gene SNPs and gastroesophageal cancer in the Hakkari region.
Immune and inflammatory genes possibly involved in the pathogenesis of severe COVID-19
(2021) Beksac, Burcu; Dincer, Selin Akad; Avdullahi, Egzon; Yaman, Derya; Terzi, Yunus Kasim; Babakurban, Seda Turkoglu; Celik, Zerrin Yilmaz; Tasci, Canturk; Sahin, Feride Iffet
Investigation of ARHGEF12 Single Nucleotide Polymorphism in Hypercholesterolemia and Primary Open Angle Glaucoma
(2020) Yaman, Derya; Takmaz, Tamer; Dincer, Selin Akad; Sahin, Feride Iffet; 0000-0001-7308-9673; AAK-2511-2021; AAC-7232-2020
Objective:To investigate the effect of single nucleotide polymorphism rs58073046 A>G within the ARHGEF12 gene in patients with hypercholesterolemia and primary open angle glaucoma. Methods: Blood samples of 20 patients with high serum cholesterol and primary open angle glaucoma (Group 1), 20 sex and age matched healthy subjects (Group 2) as controls were enrolled to the study. The ARHGEF12 gene polymorphism was determined by polymerase chain reaction and DNA sequence analysis. The data were assessed by descriptive statics and Fisher exact x(2) test. Results: The homozygous wild type genotype (AA) was identified in 95 % of Group 1 versus 100 % of Group 2. The homozygous mutant genotype (GG), presented the highest prevelance in Group 1 (5%), although the difference was not statistically significant between groups (p=0.5). Conclusion: This is the first study to identify the role of ARHGEF12 gene variant in the risk of hypercholesterolemia and POAG. Our results showed that there is no association between rs58073046 A>G polymorphism and disease development.
Investigation of Toll Like Receptor-7 Gene (TLR-7) Mutations in COVID-19 Patients
(2021) Dincer, Selin Akad; Beksac, Burcu; Avdullahi, Egzon; Yaman, Derya; Terzi, Yunus Kasim; Babakurban, Seda Turkoglu; Celik, Zerrin Yilmaz; Tasci, Canturk; Sahin, Feride Iffet
Kanser olgularında ve ailesel kanser yatkınlığı nedeniyle klinik ekzom dizi analizi yapılan olgularda sitokinler ve ilişkili sinyal yolaklarındaki değişiklikler
(Başkent Üniversitesi Sağlık Bilimleri Enstitüsü, 2022) Yaman, Derya; Şahin, Feride İffet
Kontrolsüz hücre büyümesi ve çoğalması ile karakterize olan kanser, birçok etyolojik faktöre bağımlı kompleks ve çok aşamalı genetik bir hastalıktır. Kanser ve inflamasyon arasındaki ilişki karmaşık olmasına rağmen, epidemiyolojik çalışmalar, inflamatuar ve enfeksiyöz hastalıkların kanser riski ile ilişkili olduğunu göstermektedir. İmmün sistem, patojenlere karşı vücut savunmasının yanı sıra, kanser oluşumu ve yayılımında da önemli bir düzenleyicidir. Tümör mikroçevresi immün sistem ve kanser hücrelerinin etkileşiminde kritik öneme sahiptir. Tümör mikroçevresinde immün yanıtın önemli modülatörlerinden sitokin ve oksidan moleküllerin dinamik etkileşimi, kronik inflamasyon oluşumuna aracılık ederek tümör prognozunu etkiler. Kanser immünogenetiğini araştıran güncel çalışmalar, tümör mikroçevresindeki bu moleküler değişiklikleri kanser hastalarının tanı ve prognozunda önemli biyobelirteçler olarak kabul etmektedir. Bu nedenle bu çalışmada kanser tanısı almış hasta grubunda ve ailesel kanser öyküsü nedeniyle tarama amaçlı klinik ekzom dizi analizi yapılmış olgularda sitokin ve ilişkili sinyal yolaklarında görevli gen varyantlarının incelenmesi ve sonuçların klinik bulgularla ilişkilendirilmesi amaçlanmıştır. Verilerin istatistiksel analizinde tanımlayıcı testlerden yararlanılmıştır. Çalışmamızda klinik ekzom dizi analizi endikasyonları sırasıyla invaziv duktal meme kanseri (%40, n=12/30), ailesel kanser öyküsü pozitifliği (%26.7, n=8/30), over kanseri (%13.3, n=4/30), endometriyum kanseri (%3.3, n=1/30), over ve endometriyum kanseri (%3.3, n=1/30), meme fibroblastik hiperplazisi (%3.3, n=1/30), meme ve mide kanseri (%3.3, n=1/30), mide kanseri (%3.3, n=1/30) ve gastrointestinal stromal tümörü (%3.3, n=1) tanılarını kapsamaktadır. Klinik ekzom dizi analizine göre tüm kohortta kanser ile ilişkili genlerde varyant tespit edilme oranı %83.3 (n=25/30) iken, sitokin ve ilişkili sinyal yolaklarını içeren genlerde varyant tespit edilme oranı %40 (n=12/30) idi. Klinik ekzom dizi analiz sonuçlarına göre hücre büyümesi ve çoğalması ile DNA onarımında görevli tümör baskılayıcı ve onkogenik fonksiyona sahip genlere ek olarak, mitokondriyal, lizozomal fonksiyonlarda görevli genlerde de (ALK, ATM, BRCA2, CDKN2A, CHEK2, ERBB2, ERCC2, IGF2R, KIT, LZTR1, MET, MN1, MSH5, MUTYH, MYH1, NF1, NOTCH, NQO1, PARK2, PDGFRA PMS1, POLE, PTCH1, RET, RUNX1, TP53, TSC1, TYR) varyasyon tespit edildi. Bu gen değişimlerine eşlik eden sitokin ve ilişkili sinyal yolaklarında görevli gen varyantları da belirlendi. Bu genler tümör mikroçevresi ve immün yanıt dengesinde etkisi literatürde gösterilmiş olan CCR9, CXCR1, ILDR1, IL-2Rɣ, IL-6R, IL-7R, IL-10/10RB, IL-21R, IRAK3, IRAK4, SMAD3/6, STAT3, TGF-β1, TLR2 genlerini kapsamaktadır. Özellikle DNA onarımında görevli tümör baskılayıcı gen ve onkogen değişimlerine eşlik eden sitokin ve ilişkili sinyal yolaklarında görevli gen polimorfizmleri 7 kanser tanısı almış hastamızda tespit edilmiştir. Tümör baskılayıcı gen ve onkogen varyantlarına eşlik eden sitokin gen varyantları immünreaktif tümör mikroçevresi ve genomik kararsızlık arasındaki bağlantıyı desteklemektedir. Çalışmamızın sınırlı örneklem büyüklüğüne rağmen, sonuçlarımız klinik ekzom dizi analizinin kanser immünogenetiğini aydınlatmada önemli bir moleküler genetik test olduğunu ve verilerimizin fonksiyonel çalışmalarla desteklenmesi gerektiğini göstermektedir. Cancer, which is characterized by uncontrolled cell growth and proliferation, is a complex and multistage genetic disease dependent on many etiological factors. Although the relationship between cancer and inflammation is complex, epidemiological studies show that inflammatory and infectious diseases are associated with cancer risk. The immune system is an important regulator in formation and spreading of cancer, as well as the body's defense against pathogens. The tumor microenvironment is critical in the interaction of the immune system and cancer cells. The dynamic interaction of cytokine and oxidant molecules, which are important modulators of the immune response in the tumor microenvironment, affects tumor prognosis by mediating the formation of chronic inflammation. Current studies investigating cancer immunogenetics accept these molecular changes in the tumor microenvironment as important biomarkers in the diagnosis and prognosis of cancer patients. Therefore, in this study, it was aimed to examine the gene variants involved in cytokine and related signaling pathways and to correlate the results with clinical findings in the patient group diagnosed with cancer and in patients who underwent clinical exome sequencing analysis for screening purposes due to familial cancer history. Descriptive tests were used in the statistical analysis of the data. In our study, the indications for clinical exome sequencing analysis were invasive ductal breast cancer (40%, n=12/30), familial cancer history positivity (26.7%, n=8/30), ovarian cancer (13.3%, n=4/30), endometrial cancer (3.3%, n=1/30), ovarian and endometrial cancer (3.3%, n=1/30), breast fibroblastic hyperplasia (3.3%, n=1/30), breast and stomach cancer (3.3%, n=1/30), stomach cancer (3.3%, n=1/30) and gastrointestinal stromal tumor (3.3%, n=1) respectively. According to clinical exome sequencing analysis, the rate of variant detection in cancer-related genes in the entire cohort was 83.3% (n=25/30), while the rate of variant detection in genes containing cytokine and related signaling pathways was 40% (n=12/30). According to the results of clinical exome sequencing analysis, in addition to genes with tumor suppressor and oncogenic functions in cell growth and proliferation and DNA repair, variation was also detected in genes involved in mitochondrial and lysosomal functions (ALK, ATM, BRCA2, CDKN2A, CHEK2, ERBB2, ERCC2, IGF2R, KIT, LZTR1, MET, MN1, MSH5, MUTYH, MYH1, NF1, NOTCH, NQO1, PARK2, PDGFRA, PMS1, POLE, PTCH1, RET, RUNX1, TP53, TSC1, TYR). The gene variants involved in cytokine and related signaling pathways accompanying these gene changes were also determined. These genes include CCR9, CXCR1, ILDR1, IL-2Rɣ, IL-6R, IL-7R, IL-10/10RB, IL-21R, IRAK3, IRAK4, SMAD3/6, STAT3, TGF-β1 and TLR2 whose effects have been shown in the literature on tumor microenvironment and immune response balance. In particular, gene polymorphisms in cytokines and associated signaling pathways accompanying tumor suppressor gene and oncogene changes involved in DNA repair were detected in 7 patients diagnosed with cancer. Cytokine gene variants accompanying tumor suppressor gene and oncogene variants support the link between immunoreactive tumor microenvironment and genomic instability. Despite the limited sample size of our study, our results show that clinical exome sequencing analysis is an important molecular genetic test in elucidating cancer immunogenetics and our data should be supported by functional studies.