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Öğe CYP2C9 ve VKORC1 genlerinin prostat kanseri etiyolojisindeki rollerinin araştırılması(2019) Arslan, Ali Osman; Düzenli, SelmaAmaç: Çalışmamızda, Sitokrom p450 enzimlerini kodlayan CYP ve vitamin K epoksit redüktaz kompleks subünit 1 enzimini kodlayan VKORC1 genlerinin alt gruplarındaki tek nükleotit polimorfizmlerinin bireysel ve ortak etkilerinin prostat kanseri hastalarında araştırılması amaçlanmıştır. Gereç ve Yöntem: Çalışmamıza 48 prostat kanseri tanılı erkek hasta ve 48 sağlıklı erkek birey dâhil edildi. Hasta grubu prostat tanısı almış yaş aralığı 49-86 olan gönüllü bireylerden, kontrol grubu ise prostat kanseri olmadığı belirlenmiş, 51-86 yaş grubundaki gönüllü bireylerden seçilmiştir. Katılımcıların genomik DNA’larının PCR ürünleri mikroarray yöntemi ile ayrıntılı olarak genotiplenmiştir. Bulgular: CYP2C9 ve VKORC1 enzimlerini kodlayan genlerin alt gruplarının polimorfizm karşılaştırmaları hasta ve kontrol grubu arasında yüzde olarak önemli farklar göstermiştir. Örneğin VKORC1 6853 G>C polimorfizmi için kontrol grubunda CC alleli %25 iken hasta grubunda %34,5 olarak tespit edildi. Ayrıca CYP2C9 *3 A>C değişimi için kontrol grubunda CC alleli %79,16 iken hasta grubunda %87,5 olarak tespit edilmiştir. Sonuç: Çalışmamızda yüzde olarak hasta ve kontrol grubunda önemli farklar görülmüştür. CYP2C9 ve VKORC1 geninin alt gruplarının analizleri sonucunda istatistiksel anlamlılık tespit edilmemiştir. Bunun sebebinin örnek sayısı azlığı ile alakalı olduğu ve ileri çalışmaların konuyu aydınlatacağı düşünülmüştür.Öğe Development of venous thromboembolism in patients with hereditary thrombophilic risk factors and evaluation of genetic and biochemical parameters affecting development of venous thromboembolism(2020) Korkmaz, Ufuk Turan Kürşat; Çetinkaya, Ayhan; Yüksel, Ahmet; Velioğlu, Yusuf; Uçaroğlu, Erhan Renan; Arslan, Ali Osman; Erdem, KemalettinObjectives: To evaluate patients diagnosed with venous thromboembolism (VTE) in terms of hereditary thrombophilic risk factors and to assess genetic and biochemical factors affecting the development of VTE. Methods: Sixty patients with VTE and 23 control subjects without VTE were retrospectively evaluated. Prevalence of thrombophilic risk factors and parameters like demographic data, clinical follow-up duration were examined with genetic, biochemical and radiological investigations. Results: Mutations were detected in the genes of Factor V Leiden in 37.4%, Factor II in 13.4%, Methylenetetrahydrofolate reductase C677 in 47.5%, Methylenetetrahydrofolate reductase A1298C in 53.3%, Plasminogen activator inhibitor-1 in 31.6%, Angiotensin converting enzyme in 39.0%, and Factor V H1299R in 8.3% of patients. Protein C deficiency was detected in 25 patients (41.7%), free Protein S deficiency was detected in 25 patients (41.7%) in study group and 3 subjects (13.0%) in control group, and this difference was statistically significant (p=0.023). Antithrombin III deficiency was detected in 1 patient (1.7%) in study group. Elevated homocysteine was higher in study group compared to controls, and the difference was statistically significant (p=0.02). Conclusion: Determination of hereditary risk factors in VTE patients will provide family members who have hereditary risk factors, but did not suffer attack to be protected against thromboembolic attacks by taking simple measures against acquired factors.Öğe Evaluation of patients with nasal polyps about the possible association of desmosomal junctions, RORA and PDE4D gene(Verduci Publisher, 2013) Apuhan, Tayfun; Gepdiremen, Selma; Arslan, Ali Osman; Aktaş, GülaliOBJECTIVES: Nasal polyposis is chronic inflammatory disease of the nasal mucosa of the nose and sinuses, often associated with chronic non-allergic rhinitis, aspirin intolerance and non-allergic asthma. The etiology of nasal polyposis is unknown. Multiple factors contribute to the development of nasal polyps including genetic predisposition. PATIENTS AND METHODS: This study was conducted on patients applied due to nasal polyps. Blood samples were collected peripheral vein and stored at 4 C until analysis for DNA extraction. Genomic DNA was extracted from peripheral blood by a standard method, samples were studied in real time PCR. All patients were evaluated about the possible association of DSG1 (rs7236477-G, 96 rxn), DSG3 (rs1941184-C, 96 rxn), PDE4D (rs1588265) and RORA (rs11071559) gene. RESULTS: 32 patients (17 male, 15 female) with nasal polyposis were included to the study. The mean age was 34.9 +/- 17.7 years, ranging between 18 and 55 years. Control group was consisted with 50 healthy volunteers without a history of nasal polyp. DSG1, DSG3 and RORA values of the study group were not statistically different from control group (p > 0.05). PDE4D values of the study group were significantly different from control group (p < 0.05). CONCLUSIONS: Multiple factors contribute to the pathogenesis of nasal polyps including genetic predisposition. The PDE4D family has gained interest in the complex pathogenesis of nasal polyposis. This is likely linked to the mucosal inflammatory response.Öğe Investigation of variants of critically important antioxidant enzyme genes in patients with polycystic ovary syndrome(2019) Arslan, Ali Osman; Çelik, Faruk Ömer; Küçükhüseyin, Özlem; Duran, Bülent; Diramali, Murat; Zeybek, Şakir Ümit; Düzenli, Selma GepdiremenAim: To investigate the possible effects of polymorphisms in genes encoding some importantantioxidant enzymes such as super oxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPX1),endothelial NOS (eNOS) and catalase (CAT) in patients with polycystic ovary syndrome (PCOS).Methods: Peripheral blood of 100 patients with PCOS and 100 healthy control group were collected,Polymorphisms in related genes was investigated by using polymerase chain reaction-restrictionfragment length polymorphism. In addition, the related biochemical values of the patients were alsoinvestigated.Result: In our study there is no significant results for SOD2 gene but the results obtained betweenGPX1, eNOS and CAT genes were significant. Fasting blood sugar (FBS), insulin, triglyceride, waistcircumference and dehydroepiandrosterone sulphate (DHEAS) were found to be significant with thedisease, whereas follicle-stimulating hormone (FSH) was found to be effective in preventing thedisease.Conclusions: These findings suggest that polymorphisms in genes encoding GPX1, eNOS and CATenzymes may be associated with PCOS. Additionally, it is thought that the genes of FBS, triglyceride,insulin, DHEAS and waist circumference are important in the pathogenesis of the disease in thepresence of homozygous mutation.Öğe Otosclerosis and vitamin D receptor gene polymorphism(W B Saunders Co-Elsevier Inc, 2013) Yıldırım, Yavuz Selim; Apuhan, Tayfun; Düzenli, Selma; Arslan, Ali OsmanObjective: The possible genetic relationship between otosclerosis and Vitamin D Receptor (VDR) gene polymorphism is uncertain. The aim of this study is to assess association between otosclerosis and VDR gene polymorphisms. Study Design: Case control Studies. Setting: Tertiary referral center. Subjects and Methods: Clinical diagnosis of stapes fixation was based on otoscopic, audiometric, tympanometric and surgical findings. We identified 25 eligible patient and 60 controls to investigate the association of the VDR gene polymorphisms FokI, BsmI, ApaI, and Tag I with otosclerosis. The patient and control DNA was genotyped for, VDR Bsm I (rs1544410), VDR Apo I (rs7975232), VDR Tag I (rs731236) and VDR Fok I (rs2228570) gene. Primer, simple probe sequences was genotyped by RT-PCR restriction fragment length polymorphism. Results: There was a statistically significant association between VDR gene and otosclerosis in polymorphism Tag I, Apo I and Bsm I. There was no significant association between VDR gene and otosclerosis in polymorphism Fog I. Conclusion: Three polymorphisms (Tag I, Apa I and Bsm I) in the VDR gene appear to be associated to susceptibility to otosclerosis disorder with otosclerosis patients. (C) 2013 Elsevier Inc. All rights reserved.Öğe Polymorphisms in MMP-2 and TIMP-2 in Turkish patients with prostate cancer(2014) Yaykaşlı, Kürşat Oğuz; Kayıkçı, Muhammet Ali; Yamak, Nesibe; Soğuktaş, Hatice; Düzenli, Selma; Arslan, Ali Osman; Metin, AhmetAim: Prostate cancer is the most commonly diagnosed malignancy and the second most common cause of cancer deaths in the Western male population. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) modulate the remodeling of the extracellular matrix (ECM). The imbalance between MMPs and TIMPs may lead to an emergence of pathological processes such as cancer. In this study, the association between TIMP-2 (–418 G/C) and MMP-2 (–1306 C/T) polymorphisms and prostate cancer in the Turkish population was investigated. Materials and methods: Sixty-one prostate cancer patients and 46 healthy subjects were included in the study. DNA was isolated from 2 mL of peripheral blood taken from subjects, and genotypes were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method. Results: The TIMP-2 –418 (GC) genotype was found in 15 cases (32.6%) in the control group and in 9 cases (14.8%) in the patients group, and statistical significance was determined (P = 0.037, OR = 0.346). The MMP-2 –1306 (CT) genotype was found 2.17 times more in the patient group than in the control group (P = 0.149, OR = 2.17). Conclusion: Our results show that the TIMP-2 –418 (GC) genotype had a putative protective effect against prostate cancer.Öğe Sitokrom p450 enzimlerini kodlayan genlerin (CYP) ve vitamin K epoksit redüktaz kompleks subünit1 enzimini kodlayan genin (VKORC1) varyasyonlarının prostat kanseri etiyolojisindeki rollerinin araştırılması(Bolu Abant İzzet Baysal Üniversitesi, 2012) Arslan, Ali Osman; Gepdiremen, Selma DüzenliProstat kanseri multifaktöriyel bir hastalık olup, ortaya çıkışında etnik farklılıklar, ileri yaş, sigara kullanımı, beslenme ve genetik faktörler bulunmaktadır. Çeşitli ülkelere bakıldığında prostat kanseri akciğer kanserinden sonra en sık görülen ve ölümcül olan ikinci kanser türüdür. Değişik çalışmalarda, örneğin hücre sistemleri ya da hayvan modelleri üzerinde prostat kanseri ile ilgili çalışmalar yapılmıştır.CYP450 enzim seviyeleri genetik kontrol altındadır. Sitokrom p450 sistemi ve bu sistemin alt ünitelerinden CYP2C9 genindeki polimorfizmlerin bazılarının atriyal fibrilasyon, pulmoner emboli, strok, venöz tromboz, koagülasyon bozuklukları, kardiyovasküler hastalık, depresyon, diabetes mellitus, ilaç toksisitesi, epilepsi, hipertansiyon, şizofreni gibi hastalıklara yatkınlık sağladıkları bildirilmiştir.Vitamin K epoksit redüktaz kompleks subünit 1 (VKORC1) indirgenmiş vitamin K'nın yeniden üretilmesini kontrol eden vitamin K'nın siklus enzimidir. Vitamin K epoksit redüktaz kompleks subunit 1 (VKORC1), K vitamini bağımlı hemostazda önemli bir rol oynamaktadır. VKORC1 geninin dolaylı yollardan kanserli hücrelerde anjiogenezde rol oynadığı ileri sürülmektedir.Bu sebeple bu çalışmada CYP2C9 ve VKORC1 genlerindeki polimorfizmlerin prostat kanseri etyolojisindeki rolleri araştırıldı. 48 kontrol ve 48 hasta üzerinde yapılan çalışmada CYP2C9 ve VKORC1 genlerinin alt varyantlarındaki değişimlerin prostat kanseri üzerinde etkilerinin olup olmadığı araştırıldı. Sonuç olarak, CYP2C9 geninin 6, VKORC1 geninin 8 adet polimorfizmi istatistiksel olarak anlamlı olmamakla birlikte, sayısal ve yüzde olarak hasta ve kontrol grubunda önemli fark göstermiştir. Bu sonuçların yorumunda, hasta ve kontrol grubunun sayısal küçüklüğü göz önünde bulundurulmalıdır.
