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The association of Intron 4 VNTR and Glu298Asp polymorphisms of the nitric oxide synthetase 3 gene and vasculogenic erectile dysfunction in Turkish men
(Taylor & Francis Inc, 2019) Arda, Ersan; Ay, Arzu; Akdere, Hakan; Akdeniz, Esra
Several studies have focused on the impaired role of endothelial nitric oxide synthase (NOS3) gene polymorphism and its association to erectile dysfunction (ED). However, currently controversial results have been reported due to their significant heterogeneity. The present study aimed to assess the genotypic distribution and the allelic frequency of Intron 4 VNTR and Glu298Asp gene polymorphisms in vasculogenic ED patients compared to healthy controls of a specific region of Turkey. A total of 75 patients with ED (median age: 56, IQR:10.5) and 75 healthy controls (median age: 56, IQR:10.5) were prospectively analyzed. All subjects were equally evaluated by the same physician with detailed history-taking, physical examination, International Index of Erectile Function (IIEF) questionnaire, and blood tests (incl. glucose, testosterone, triglyceride and total cholesterol level). Those with an IIEF score under 26 were considered to have ED, by classifying them according to their scores as mild (22-25), moderate (11-21) and severe (1-10) ED. Color doppler ultrasonography was carried out in patients with an IIEF score <22. Hypertension, diabetes mellitus, coronary artery disease, and smoking status were significantly associated with the ED group compared to control subjects with p values of <0.001, <0.001, 0.002 and <0.001, respectively. Overall genotype frequencies was 47 (31%) a/a, 22 (15%) a/b, 82 (55%) b/b for Intron 4 VNTR and 56 (37%) GG, 78 (52%) GT, 16 (11%) TT for the Glu298Asp polymorphism. The frequencies of Intron 4 VNTR a/a allele and Glu298Asp GT allele were associated with severe ED, while a/b and TT were associated with moderate or mild, and b/b and GG were associated with no ED. In contrast to Glu298Asp, statistically significant differences in genotypic frequencies of Intron 4 VNTR gene polymorphism between ED and control subjects was established.
Calcitonin related polypeptide alpha gene polymorphisms according to plasma total homocysteine levels in ischemic stroke patients of Trakya Region
(Taylor & Francis Ltd, 2017) Alkanli, Nevra; Sipahi, Tammam; Ay, Arzu; Guldiken, Baburhan; Bakir, Alev; Alkanli, Suleyman Serdar; Celebi, Canan
The aim of this study was to determine the genotype distributions of calcitonin related polypeptide alpha (CALCA) gene polymorphisms according to the plasma total homocysteine levels in ischemic stroke patients and patient subtypes selected from Trakya Region. The study included 82 patients and 92 healthy controls. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to determine the genotype distributions of CALCA gene polymorphisms. The plasma total homocysteine levels were measured by Immulite 2000XPi homocysteine kits. Significant differences were not found between the group of patients and the control group in terms of CALCA gene polymorphisms genotype distributions (p > 0.05). Significant differences were not found between ischemic stroke patients and healthy controls, in the patient subtypes with ischemic stroke in respect to the CALCA gene polymorphisms genotype distributions according to the plasma total homocysteine levels (p > 0.05). This suggests that the CALCA gene polymorphisms genotype distributions studied according to the plasma total homocysteine levels could not likely be considered a genetic risk factor for ischemic stroke development.
Covid-19 Enfeksiyonunun ARDS komplikasyonunda IL-10 ve IL-10 (-1082G/A) Gen Varyasyonunun Potansiyel Rollerinin İncelenmesi
(2021) Alkanlı, Nevra; Ay, Arzu
COVID-19 yeni koronavirüs hastalığı olarak bilinmektedir ve COVID-19 enfeksiyonundan kaynaklanan komplikasyonlar yaş, cinsiyet ve komorbiditeler gibi çeşitli faktörlere bağlı olarak değişmektedir. Tüm yaş gruplarını etkileyebilen COVID-19 enfeksiyonu etkilenen popülasyonların bireysel özelliklerine bağlı olarak doğrulanmış vakaların bir kısmında ciddi rahatsızlık ve ölüm nedeni olarak ortaya çıkabilmektedir. Bu enfeksiyon özellikle yaşlı bireylerde ve hipertansiyon, diabetes mellitus, astım gibi komorbiditelere sahip kişilerde daha şiddetli seyretmektedir. Ancak COVID-19 enfeksiyonunun oldukça genç olan bireylerde de görülebileceği bildirilmiştir. Bu yüzden doku proteinlerinin ekspresyon düzeyleri gibi intrinsik faktörlerin yanısıra, genetik varyasyonlar gibi genetik faktörler de enfeksiyon patogenezine katkıda bulunabilmektedir. COVID-19 hastalarının yarısından fazlasında en sık görülen komplikasyonlardan biri yoğun bakım tedavisi gerektiren ARDS (Akut Solunum Sıkıntısı Sendromu) dir. COVID-19’da viral enfeksiyona yanıt olarak İnterlökin-10 (IL-10) gibi sitokinler salınmaktadır. COVID-19 enfeksiyonu sırasında gelişen sitokin fırtınası kontrolsüz inflamasyona neden olmaktadır. Böylece çoklu organ yetmezlikle-ri gelişebilmekte ve ARDS ile ilişkili sendromlar indüklenebilmektedir. Sitokin fırtınası COVID-19 hastalarında anlamlı derecede artmış IL-10 düzeyleri ile ilişkilendirilmiştir. ARDS patogenezinde inflamasyon önemli bir belirteçtir. Proinflamatuar ve antiinflamatuar sitokinler arasındaki dengesizlik sonucunda ARDS gelişebilmektedir. IL-10 geninin promotör bölgelerindeki genetik varyasyonlar sonucunda IL-10 mRNA ve protein düzeylerinde değişiklikler ortaya çıkmaktadır. IL-10’un patolojik proinflamatuar işlevi engelleyerek COVID-19 enfeksiyonundaki mortalitenin azalmasına katkı sağlayabileceği düşünülmektedir. ARDS gelişen COVID-19 hastalarında IL-10 geninin promotör bölgesinde tanımlanan IL-10 (-1082G/A) gen varyasyonu genotip dağılımlarına göre IL-10 ekspresyon düzeylerinin belirlenmesi, ARDS’nin patolojik mekanizmalarının daha iyi anlaşılabilmesi ve ARDS’ye yönelik terapötik stratejilerin geliştirilebilmesi bakımından oldukça önemlidir. Bu derlemede COVID-19 enfeksiyonunda gelişen ARDS komplikasyonunda IL-10 ve IL-10 (-1082G/A) gen varyasyonlarının rolünün incelenmesi amaçlanmıştır.
CRISPR/Cas9 Mediated Therapeutic Approach in Huntington's Disease
(Springer, 2023) Alkanli, Suleyman Serdar; Alkanli, Nevra; Ay, Arzu; Albeniz, Isil
The pathogenic mechanisms of these diseases must be well understood for the treatment of neurological disorders such as Huntington's disease. Huntington's Disease (HD), a dominant and neurodegenerative disease, is characterized by the CAG re-expansion that occurs in the gene encoding the polyglutamine-expanded mutant Huntingtin (mHTT) protein. Genome editing approaches include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats/Caspase 9 (CRISPR/Cas9) systems. CRISPR/Cas9 technology allows effective gene editing in different cell types and organisms. Through these systems are created isogenic control of human origin induced pluripotent stem cells (iPSCs). In human and mouse models, HD-iPSC lines can be continuously corrected using these systems. HD-iPSCs can be corrected through the CRISPR/Cas9 system and the cut-and-paste mechanism using isogenic control iPSCs. This mechanism is a piggyBac transposon-based selection system that can effectively switch between vectors and chromosomes. In studies conducted, it has been determined that in neural cells derived from HD-iPSC, there are isogenic controls as corrected lines recovered from phenotypic abnormalities and gene expression changes. It has been determined that trinucleotide repeat disorders occurring in HD can be cured by single-guide RNA (sgRNA) and normal exogenous DNA restoration, known as the single guideline RNA specific to Cas9. The purpose of this review in addition to give general information about HD, a neurodegenerative disorder is to explained the role of CRISPR/Cas9 system with iPSCs in HD treatment.
Determination of the Roles of Endothelial Nitric Oxide Synthase 4VNTR (4a/b), G894T, T786C Gene Variations in the Bladder Cancer Development
(Springer India, 2024) Ay, Arzu; Alkanli, Nevra; Cevik, Gokhan
The aim of this study is to determine the roles of eNOS gene variations in BCA development. Our study included 91 patients diagnosed with BCA and 91 healthy controls. eNOS 4VNTR (4a/b), T786C and G894T gene variations genotype distributions were determined by PCR and RFLP methods. The significant difference was determined between these groups in terms of eNOS T786C and eNOS G894T gene variations genotype distributions (p < 0.05). TT genotype for G894T gene variation and CC genotype for T786C gene variation were detected higher in patients. The CC genotype of T786C gene variation was detected significantly higher in male patients than in male controls (p < 0.05). In addition, aa-TT, ab-TT, bb-TT haplotypes of 4VNTR (4a/b)-G894T gene variations, aa-CC, ab-CC, bb-CC haplotypes of 4VNTR (4a/b)-T786C gene variations and TT-TT, TT-CC, TT-CT, GG-CC, GT-CC haplotypes of G894T-T786C gene variations were observed in patient group more than control group. The significant difference was detected between these groups in terms of eNOS (G894T-T786C) haplotypes (p < 0.05). In our study, eNOS T786C and eNOS G894T gene variations were determined important genetic risk factor in the Thrace population of Turkey.
Genetik Cyp1A1, Gstm1 polimorfizmi ve serum eser elementleri ile kolorektal kanser riski ilişkisi
(Trakya Üniversitesi Sağlık Bilimleri Enstitüsü, 2015) Ay, Arzu; Gülyaşar, Tevfik
Trakya Bölgesi’ndeki kolorektal kanserli hastalar üzerinde yaptığımız çalışmada CYP1A1, GSTM1 gen polimorfizmlerinin eser elementlerle (demir, bakır, çinko, selenyum) ilişkisinin olası etkilerini belirlemeyi amaçladık. Çalışma 165 kolorektal kanserli hasta ve 171 sağlıklı kontrol grubundan oluşturuldu. CYP1A1 ve GSTM1 gen polimorfizmleri için Gerçek Zamanlı Polimeraz Zincir Reaksiyonu kullanıldı, serum eser element düzeyleri Atomik Absorbsiyon Spektrofotometresi ile plazmada lipit peroksidasyonu ise spektrofotometrik yöntemle değerlendirildi. Hipertansiyon, diyabet, sigara, alkol tüketimi ve aile kanser öyküleri hastalık aleyhinde risk faktörleri olabilir. Bu çalışmada GSTM1 (rs:12068997) gen polimorfizmindeki GG genotipleri kolorektal kanserli hastalar için genetik risk oluşturabilir. Kolorektal kanserli grupta serum çinko, bakır düzeyleri, bakır/çinko oranı ve malondialdehit anlamlı derecede yüksek ve serum selenyum düzeyleri düşük bulundu. CYP1A1’in (rs:2605345), (rs:1048943) ve (rs:1799814) ile GSTM1’in (rs:11278559), (rs:12068997) polimorfizmlerinin genotipleri ile serum bakır, çinko, bakır/çinko oranları hasta grubunda daha yüksek olacak şekilde anlamlı farklar bulundu. Ancak bu genotipler ile serum demir düzeyleri arasında ilişki bulunmadı. Serum selenyum düzeyleri kolorektal kanserli grupta anlamlı derecede düşük bulundu. Bulgularımıza göre CYP1A1 veya GSTM1 genotipleri, serum eser elementlerin (bakır, çinko, selenyum, bakır/çinko) düzeyleri arasındaki ilişkiyi önemli ölçüde değiştirebilir ve bu kolorektal kanserin ilginç patogenezini gösterebilir.
Hipertansiyonlu hastalarda anjiyotensinojen m235t/t174m gen polimorfizminin araştırılması
(Trakya Üniversitesi Sağlık Bilimleri Enstitüsü, 2007) Ay, Arzu; Tammam, Sipahi
Genetik ve çevre faktörleriyle tetiklenen hipertansiyon Trakya bölgesinin büyük bir halk sağlığı problemidir. Son zamanlarda genetik yöntemleri kullanılarak hipertansiyon gelişmesinde olası rolü düşünülen aday genleri tespit edilmeye başlanmıştır. Anjiyotensinojen geni; Renin Anjiyotensin Sistemi'nde hipertansiyona sebep olduğu düşünülen ilk güçlü aday gendir. Anjiyotensinojendeki değişiklikler, güçlü bir damar daraltıcı etkisine sahip hormon olan anjiyotensin II ile plazmadaki anjiyotensinojen seviyelerinin değişmesine sebep olur. Bu çalışmanın amacı anjiyotensinojen genindeki M235T ve T174M polimorfizmlerinin; Türkiye'de Trakya bölgesindeki hipertansiyon olgularında; hipertansiyon gelişmesindeki rolünü tespit etmektir. Çalışmamızda M235T için 75'i hipertansiyon hastası ve 40 sağlıklı normotensif olmak üzere toplam 115 vaka incelenmiş, T174M polimorfizmi için 78'i hipertansiyon hastası ve 40 normotensif olmak üzere toplam 118 vaka incelenmiştir. Anjiyotensinojen geninin M235T ve T174M polimorfizmleri için allel spesifik polimeraz zincir reaksiyonu ve Restriksiyon Fragman Uzunluk Polimorfizmi yöntemleri kullanılmıştır. M235T ve T174M için genotip ve allel dağılımı hipertansiyon hastalarında ve ve normotensiflerde ki test değerlendirme sonucu aynı bulunmuştur. Anjiyotensinojen geninin M235T ve T174M polimorfizmlerinin hipertansiyonla ilişkisi bulunamamıştır. Anahtar Kelimeler: Anjiyotensinojen, M235T, T174M, Hipertansiyon, Polimorfizm Hypertension, which is a disease multifactorially triggered by genetic and environmental factors, is a major public health concern in Trakya Region in Turkey. Recent advances in genetic determination of human essential hypertension are discussed by reviewing the candidate genes. Angiotensinogen gene in renin angiotensin system was first described as a strong candidate associated with the onset of hypertension. Variation in the angiotensinogen, which is the precursor of potent vasoaktive hormone angiotensin II, has been associated with variation in plasma angiotensinogen levels. The aim of this study was to investigate the correlation between the M235T and T174M polymorphisms of the angiotensinogen gene and their roles in developing of essential hypertension in Turkish subjects in Trakya region. Our study involved 115 subjects, 75 hypertensive and 40 age matched normotensive for M235T gene polymorphism and 118 subjects, 78 hypertensive and 40 age matched normotensive for T174M gene polymorphism. Consents were obtained from all the participated subjects. M235T and T174M polymorphisms of the angiotensinogen gene was investigated using allele specific polymerase chain reaction assay and restriction fragment length polymorphism . The genotype and allele distribution of the M235T and T174M variant was same in hypertensives and age matched normtensives. The M235T and T174M variant of the angiotensinogen is not associated with essential hypertension. Key words: Angiotensinogen, M235T, T174M, Hypertension, Polymorphism
Investigation of Relationship Between Small Noncoding RNA (sncRNA) Expression Levels and Serum Iron, Copper, and Zinc Levels in Clinical Diagnosed Multiple Sclerosis Patients
(Springer, 2023) Ay, Arzu; Alkanli, Nevra; Atli, Engin; Gurkan, Hakan; Gulyasar, Tevfik; Guler, Sibel; Sipahi, Tammam
In our study, we aimed to investigate the relationship between microRNA (miRNA) expression levels and serum iron (Fe), copper (Cu), and zinc (Zn) levels in Multiple sclerosis (MS) patients. Total RNA was isolated from peripheral venous blood containing ethylenediaminetetraacetic acid (EDTA) of MS patients and controls. Total RNA was labeled with Cy3-CTP fluorescent dye. Hybridization of samples was performed on microarray slides and arrays were scanned. Data argument and bioinformatics analysis were performed. Atomic absorption spectrophotometer method was used to measure serum Fe, Cu, and Zn levels. In our study, in bioinformatics analysis, although differently expressed miRNAs were not detected between 16 MS patients and 16 controls, hsa-miR-744-5p upregulation was detected between 4 MS patients and 4 controls. This may be stem from the patient group consisting of MS patients who have never had an attack for 1 year. Serum iron levels were detected significantly higher in the 16 MS patients compared to the 16 controls. This may be stem from the increase in iron accumulation based on inflammation in MS disease. According to the findings in our study, hsa-miR-744-5p upregulation has been determined as an early diagnostic biomarker for the development together of insulin resistance, diabetes mellitus associated with insulin signaling, and Alzheimer's diseases. Therefore, hsa-miR-744-5p is recommended as an important biomarker for the development together of diabetes mellitus, Alzheimer's disease, and MS disease. In addition, increased serum Fe levels may be suggested as an important biomarker for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and MS disease.
Investigation of roles of IL-8 (+781 C/T) and MMP-2 (-735 C/T) gene variations in early diagnosis of bladder cancer and progression
(Springer, 2023) Alkanli, Nevra; Ay, Arzu; Cevik, Gokhan
Background The aim of our study is to investigate the roles of IL-8 (+ 781 C/T) and MMP-2 (-735 C/T) gene variations in early diagnosis and progression of BCA. Methods Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) methods were used to determine the genotype distributions of IL-8 (+ 781 C/T) and MMP-2 (-735 C/T) gene variations. Results In our study, the genotype distributions of IL-8 (+ 781 C/T) and MMP-2 (-735 C/T) gene variations were not found to be significantly different between the patient and control groups. In addition, C and T allele frequencies for these gene variations were not different from the Hardy-Weinberg distribution in patient and control groups. However, when the combined genotype analyzes for these gene variations were evaluated, CC-CC and CT-CC combined genotypes for + 781 C/T / -735 C/T gene variations were observed significantly more in the patient group compared to other genotypes. Conclusion Although IL-8 (+ 781 C/T) and MMP-2 (-735 C/T) gene variations were not found to be genetic risk factors in the Thrace population in our study, CC-CC and CT-CC combined genotypes were determined as genetic risk factors for BCA susceptibility. The combined genotypes obtained as a result of the combined genotype analysis of these genetic variations that are effective in tumor progression may be considered to be important biomarkers for the early diagnosis and progression of BCA.
Investigation of The Effects of Serum Iron and Copper Levels in Ischemic Stroke Disease Development
(2021) Ay, Arzu; Alkanlı, Nevra; Kehaya, Sezgin
Objective: Ischemic stroke is characterized by loss of focal cerebral function due to impaired of brain-blood flow. Environmental factors and genetic factors may be effective together in the pathogenesis of ischemic stroke. Trace elements are important components of the biological structure, and toxic effects may occur when these trace elements are taken in more than the amount required for biological functions. The risk of neurological diseases such as ischemic stroke may increase as a result of imbalances in trace element levels. Therefore, the aim of this study is to investigate the effects of serum iron and copper levels in the development of ischemic stroke disease. Materials and Methods: Our study consisted of 20 ischemic stroke patients and 36 healthy controls. Serum iron and copper levels measurements were performed using atomic absorption spectrophotometer method. Results: Serum iron and copper levels were detected significantly lower in the patient group with ischemic stroke compared to the healthy control group. However, the significant difference was not determined in comparison of serum copper and iron levels according to gender between patient with ischemic stroke and healthy control groups. Conclusion: In our study, it was determined that serum iron and copper levels may be effective risk factors for ischemic stroke disease. Thus, it was concluded that serum iron and copper trace element levels may be important biomarkers that may be evaluated in the diagnosis, prognosis and treatment of ischemic stroke.
Investigation of the relationship between GSTM1 gene variations and serum trace elements, plasma malondialdehyde levels in patients with colorectal cancer
(Springer, 2021) Ay, Arzu; Gulyasar, Tevfik; Alkanli, Nevra; Sipahi, Tammam; Cicin, Irfan; Kocak, Zafer; Sut, Necdet
Background The aim of this study is to investigate of the relationship between GSTM1 gene variations and serum trace elements, plasma malondialdehyde levels in patient with colorectal cancer. Mateials and Methods. Genotype distributions of GSTM1 gene variations were determined using real-time polymerase chain reaction method. Serum trace element levels were determined using atomic absorption spectrophotometer method and plasma MDA levels were measurement by spectrophotometric method. Results Serum Cu levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GA heterozygous genotype of the GSTM1 (rs 112,778,559) gene variation compared to healthy controls (p < 0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in patients carrying GG homozygous genotype of the GSTM1 (rs 112778559) gene variation compared to healthy controls carrying same genotype (p < 0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GG homozygous genotype of the GSTM1 (rs 12068997) gene variation compared to healthy controls (p < 0.05). On the other hand, serum Se levels were detected significantly lower in CRC patients carrying GA heterozygous and GG homozygous genotypes for GSTM1 (rs 112,778,559) and (rs 12,068,997) gene variations compared to healthy controls (p < 0.05). Conclusion In our study, the evaluation of serum Cu, Zn and Se trace element levels and plasma MDA levels according to GSTM1 gene variations genotype distributions were enabled to obtain important biomarkers in terms of CRC development and progression.
Investigation of The Relationship Between IL-18 (-607 C/A), IL-18 (-137 G/C) Gene Variations and Ischemic Stroke Disease Development in Thrace Region of Turkey
(Taylor & Francis Inc, 2021) Alkanli, Nevra; Ay, Arzu; Kehaya, Sezgin; Sut, Necdet
Background Ischemic stroke is a clinical condition characterized by focal or global cerebral dysfunction resulting from inhibition of brain blood flow. Genetic factors play an important role in the pathogenesis of ischemic stroke. As a result of IL-18 (-607 C/A, -137 G/C) gene variations, it is thought that binding of transcription factors may be affected and IL-18 mRNA expression can be modulated. Therefore, the purpose of our study is to investigate the roles of IL-18 (-607 C/A), IL-18 (-137 G/C) gene variations in the development of ischemic stroke in Trakya Region of Turkey. Methods Our study was performed with 90 ischemic stroke patients and 89 healthy controls. Genotype distributions of IL-18 (-607 C/A, -137 G/C) gene variations were determined using polymerase chain reaction (PCR) method. Results GC genotype and CA genotype of IL-18 (-137 G/C) and IL-18 (-607 C/A) gene variations were determined higher significantly in patent group as compared with other genotypes. However, the statistically significant difference was not determined between patients with ischemic stroke and healthy control groups in terms of IL-18 (-137 G/C) and IL-18 (-607 C/A) gene variations (p> 0,05). Allele frequencies of IL-18 (-137 G/C) and IL-18 (-607 C/A) in patient and control groups were significantly different from the Hardy-Weinberg distribution (p< .001 for all). Conclusion Although these gene variations' genotype distributions were not determined as a genetic risk factor for the development of ischemic stroke, allele frequencies of IL-18 (-137 G/C) and IL-18 (-607 C/A) in patient and control groups were significantly different from the Hardy-Weinberg distribution.
Investigation of the Relationship Between IL-18 (-607 C/A), IL-18 (-137 G/C), and MMP-2 (-1306 C/T) Gene Variations and Serum Copper and Zinc Levels in Patients Diagnosed with Chronic Renal Failure
(Springernature, 2022) Ay, Arzu; Alkanli, Nevra; Ustundag, Sedat
The aim of this study is to investigate the relationship between IL-18 (- 607 C/A), IL-18 (- 137 G/C), and MMP-2 (- 1306 C/T) gene variations and serum trace element levels in patients diagnosed with CRF. Genotype distributions of IL-18 (- 607 C/A, - 137 G/C) gene variations were determined by polymerase chain reaction (PCR) method. PCR-restriction fragment length polymorphism (RFLP) methods were used to determine the MMP-2 (- 1306 C/T) gene variation genotype distributions. Serum trace element levels were determined by atomic absorption spectrophotometer method. A significant difference was found between the CRF patient and healthy control groups in terms of genotype distributions of IL-18 (- 607 C/A) and MMP-2 (- 1306 C/T) gene variations (p < 0.05). The significant difference was found between the patient and control groups in terms of serum copper and zinc levels and copper/zinc ratio (p < 0.05). The significant difference was detected between patient and control groups in terms of copper and zinc levels and copper/zinc ratio according to IL-18 (- 607 C/A), IL-18 (- 137 G/C), and MMP-2 (- 1306 C/T) gene variations and genotype distributions (p < 0.05). In addition, significant difference was determined in terms of serum copper and zinc levels and copper/zinc ratio according to haplotypes of IL-18 (- 607 C/A), IL-18 (- 137 G/C), and MMP-2 (- 1306 C/T) gene variations between patient and control groups (p < 0.05). In conclusion, evaluation of IL-18 (- 607 C/A, - 137 G/C) and MMP-2 (- 1306 C/T) gene variations and serum trace element levels together is extremely important in terms of obtaining important biomarkers in CRF early diagnosis and progression.
Investigation of the Relationship Between Ischemic Stroke Disease and Serum Zinc Levels
(Erciyes Univ Sch Medicine, 2022) Alkanli, Nevra; Ay, Arzu; Kehaya, Sezgin
Objective: The purpose of this study was to investigate the relationship between the development of ischemic stroke disease and the serum zinc level. Materials and Methods: A total of 22 ischemic stroke patients and 38 healthy controls were included in the study. Routine blood samples of both groups were centrifuged at 5000 rpm for 5 minutes and serum samples were separated from the blood. Distilled water was added to the serum samples to make a total volume of 4 mL. Vortexing was used to homogenize the total mixture and standard solutions were used to detect zinc with an atomic absorption spectrophotometer. A concentration calibration graph was created to illustrate the results. Results: The serum zinc level was significantly higher in the patient group than in the control group (p<0.05). No statistically significant relationship was determined between the serum zinc level and parameters associated with ischemic stroke risk factors and patient complications (p>0.05). However, a strong positive significant correlation was detected between hemoglobin and hematocrit parameters (r=0.936; p<0.001), a moderately positive significant correlation between C-reactive protein and chlorine parameters (r=0.445; p=0.038), a moderately positive significant correlation between sodium and chlorine parameters (r=0.522; p=0.013), and a moderately positive significant correlation between ischemic stroke duration and potassium parameters (r=0.483; p=0.023). Conclusion: The significant increase in the serum zinc level of ischemic stroke patients and the significant positive correlations in parameters associated with ischemic stroke risk factors and complications may indicate an effect on neuronal metabolism that contributes to the development of ischemic stroke.
Investigation of the relationship between MMP-1 (-1607 1G/2G), MMP-3 (-1171 5A/6A) gene variations and development of bladder cancer
(Springer, 2021) Ay, Arzu; Alkanli, Nevra; Cevik, Gokhan
Background Chronic inflammation is an important risk factor in the development of bladder cancer. It may stimulate growth and metastasis of cancer cells. The inflammatory process includes MMP activities and expression. MMP activation can be stimulated by various inflammatory cells. Pathological processes such as bladder cancer may occur due to imbalance in MMP activities. In our study, we aimed to determine the relationship between MMP-1, MMP-3 gene variations associated with chronic inflammation and the bladder cancer development. Methods Our study was carried out with 89 bladder cancer patients and 78 healthy controls. PCR-RFLP methods were applied to determine MMP-1 and MMP-3 gene variations genotype distributions. Results 1G/1G homozygous and 1G/2G heterozygous genotypes of MMP-1 gene variation were determined more in patients than controls. The 5A/5A homozygous and 5A/6A heterozygous genotypes of the MMP-3 gene variation were detected more in patients than controls. The significant difference was detected in terms of genotype distributions of MMP-1 and MMP-3 gene variations between these groups (p < 0.05). In addition to, the most common haplotype in the patient group were detected as 1G/2G-5A/6A (20.22%). Conclusion In this study, MMP-1 and MMP-3 gene variations were determined as possible genetic risk factors for bladder cancer development in the Thrace population.
Investigation of the Relationship Between MTHFR C677T Gene Variation and Serum Copper Levels in Patients Diagnosed with Parkinson's
(2022) Ay, Arzu; Alkanlı, Nevra; Güler, Sibel
Objective: In this study, we aimed to investigation of the relationship between MTHFR C677T gene variation and serum copper levels in patients diagnosed with Parkinson's. Materials and Methods: For our study, patient and control groups were formed including 63 Parkinson's patients and 32 healthy controls. Genotype distributions for MTHFR gene variation were determined and serum copper levels were measured. In these processes PCR, RFLP and atomic absorption spectrophotometer methods were applied. Results: Serum Cu levels of Parkinson's patients were found to be significantly higher than healthy controls. Although the significant difference was not found between the patient and control groups in terms of genotype distributions of the MTHFR C677T gene variation, CC homozygote genotype of this gene variation was observed significantly more than other genotypes in the patient group. In addition, the C allele frequency of this gene variation was determined significantly different from the Hardy-Weinberg distribution in Parkinson's patients. Serum copper levels of Parkinson's patients carrying CT and TT genotypes were detected significantly higher than the serum copper levels of controls carrying the same genotypes. Conclusion: In our study, in Thrace population, it was determined that the relationship between MTHFR C677T gene variation and serum copper levels may be an important factor for Parkinson's disease. In conclusion, the evaluation of MTHFR C677T gene variation genotype distributions and serum copper levels together is extremely important for prognosis of Parkinson's disease.
Investigation of the relationship between MTHFR, IRS and CALCA gene polymorphisms and development of diabetic nephropathy in patients with type 2 diabetes mellitus
(Taylor & Francis Ltd, 2018) Ay, Arzu; Alkanli, Nevra; Sipahi, Tammam; Gulyasar, Tevfik; Ustundag, Sedat; Guldiken, Sibel; Sut, Necdet
The aim of this study was to investigate the relationship between MTHFR, IRS and CALCA gene polymorphisms and development of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (DM). Our study included 93 patients with type 2 DM diagnosed as having nephropathy and 95 controls diagnosed with type 2 DM without development of DN. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to determine the genotype distributions of MTHFR, IRS and CALCA gene polymorphisms. The results showed no statistically significant difference between DN patients and type 2 DM controls in terms of genotype distributions of MTHFR (C677T, A1298C), IRS (IRS-1 Gly972Arg, IRS-2 Gly1057Asp) and CALCA T692C gene polymorphisms (p > 0.05). However, in terms of allele frequencies for the MTHFR A1298C gene, the frequency of the C allele was significantly higher in the DN patients compared to the controls (p < 0.05). In the IRS-2 Gly1057Asp gene polymorphism, the G allele frequency was significantly higher in the DN patients than in the type 2 DM controls (p < 0.05). In the DN group, the individuals with one or less mutant alleles were significantly more than in the control group in terms of the IRS-2 Gly1057Asp gene polymorphism (p < 0.05). The C allele frequency for the MTHFR A1298C gene polymorphism and the G allele frequency for the IRS-2 Gly1057Asp gene polymorphism were indicated to be potential a genetic risk factor for the development of DN in patients with type 2 DM who developed DN.
Investigation of the relationship between MTRR A66G, MTR A2756G gene variations and cell anomalies in early diagnosis and progression of bladder cancer
(Springer, 2022) Alkanli, Nevra; Ay, Arzu; Aydin, Pinar Koroglu; Cevik, Gokhan
Background The aim of this study is to investigate the relationship between MTRR A66G, MTRA2756G gene variations and cell anomalies in the early diagnosis and progression of bladder cancer. Methods PCR and RFLP methods were used to determine the genotype distributions of MTRR A66G and MTR A2756G gene variations. Peripheral smear preparations prepared from blood samples were fixed with methanol fixative and stained histochemically. Cellular morphological evaluations were made under the light microscope. Results In our study, AA-GG haplotype was observed significantly more in the patient group than control group (OR: 3.304, 95% CI: 1.023-10.665, p = 0.046). The significant increase was determined in terms of histological damage parameters in the patient group compared to the control group (p < 0.05). For multiple vacuoles damage parameter (mild score), AA genotype of MTR A2756G gene variation was significantly different compared to AA genotype of MTRR A66G gene variation (OR: 0.211, 0.049-0.912, p = 0.037). AA genotype of MTR A2756G gene variation was observed more than AA homozygous genotype of MTR A66G gene variation for giant platelets with different sizes damage parameter (mild score) (OR: 0.062, 0.017-0.228, p < 0.001). Conclusions In conclusion, in Thrace population, AA genotype of the MTR A2756G gene variation was significantly higher than the AA homozygous genotype of the MTR A66G gene variation as a genetic risk factor for the multiple vacuoles damage parameter. In addition, AA genotype of MTR A2756G gene variation was determined as a genetic risk factor for giant platelets with different sizes damage parameter.
Investigation of the roles of IL-18 (-607 C/A) and IL-18 (-137 G/C) gene variations in bladder cancer development: case-control study
(Springer, 2021) Alkanli, Nevra; Ay, Arzu; Cevik, Gokhan
Background The purpose of our study is to investigate the roles of IL-18 gene variations in bladder cancer development in Thrace population of Turkey. Methods This study was carried out with 103 bladder cancer patients and 81 healthy controls. Genotype distributions of IL-18 (-137 G/C) and IL-18 (-607 C/A) gene variations were determined using polymerase chain reaction (PCR) method. Results The CC homozygous genotype for IL-18 (-607 C/A) gene variation was significantly higher in patients with bladder cancer compared to healthy controls (OR 0.345, 95% Cl 0.186-0.639, p = 0.001). Besides this, allele frequencies of IL-18 (-137 G/C) and IL-18 (-607 C/A) gene variations in patient with bladder cancer and healthy control groups were significantly different from the Hardy-Weinberg distribution (p < 0.05). For IL-18 (-137 G/C) and IL-18 (-607 C/A) gene variations, significant difference was determined between the bladder cancer patient and healthy control groups in terms of GC-CA (OR 0.381, 95% Cl 0.203-0.714, p = 0.002), GC-CC (OR 2.147, 95% Cl 1.013-4.550, p = 0.043), GG-AA (OR 0.431, 95% Cl 0.365-0.509, p = 0.049), and GG-CC (OR 2.476, 95% Cl 1.177-5.208, p = 0.015) haplotypes. Conclusion In our study, CC genotype of IL-18 (-607 C/A) gene variation was determined as genetic risk factor for bladder cancer development. In bladder cancer patient and healthy control groups, G and C allele frequencies of IL-18 (-137 G/C) gene variation, and C and A allele frequencies of IL-18 (-607 C/A) gene variation were determined significantly different from the Hardy-Weinberg distribution.
Investigation of the Roles of MTHFR (C677T and A1298C) and MMP-2 (-1306C> T) Variations in Bladder Cancer Development
(Aves, 2023) Alkanli, Nevra; Ay, Arzu
Objective: Bladder cancer is a complex malignancy and has been associated with high morbidity. Since susceptibility to bladder cancer development differs between individuals, determining the roles of MTHFR and MMP-2 gene variations associated with this cancer is important for analyzing differences in individual susceptibility. In this study, we aimed to investigate the role of MTHFR and MMP-2 gene variations in the development of bladder cancer in the Thrace region of Turkey. Materials and methods: One hundred seventy-nine blood samples were collected, including 98 patients with bladder cancer and 81 healthy controls. DNA extraction was carried out with blood samples. Polymerase chain reaction-restriction fragment length polymorphism was applied to detect MTHFR C677T (rs 1801133), MTHFR A1298C (rs 1801131), and MMP-2 (-1306C>T) (rs 243865) gene variants. Results: For the MTHFR A1298C gene variation, CC genotype was the genetic risk factor (P =.0001), while AC genotype was the protective factor (P <.0001) in the development of bladder cancer. For the MMP-2 (-1306C>T) gene variation, TT genotype (P <.0001) and T allele (P =.0006) were genetic risk factors, while AC genotype (P =.0009) was the protective factor in the development of bladder cancer. For C677T/A1298C gene variations, CC-CC combined genotype was the genetic risk factor (P =.009), while CT-AC and CC-AC combined genotypes were potential protective biomarkers (P =.013 and P <.001, respectively). Conclusion: In our study, TT genotype and T allele were determined as genetic risk factors for MMP-2 (-1306C>T) gene variation. For C677T/A1298C gene variations, CCCC combined genotype was detected as the genetic risk factor in the development of bladder cancer.

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