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    CYB mtDNA mutations and expression status of genes in the PI3K/AKT/mTOR signaling pathway in patients with schizophrenia
    (Cukurova Univ, Fac Medicine, 2022) Dirican, Ebubekir; Uzuncakmak, Sevgi Karabulut; Ozcan, Halil
    Purpose: This study aimed to screen for cytochrome b (CYB) mitochondrial DNA (mtDNA) mutations and analyze the mRNA expressions of genes in the PI3K/AKT/mTOR signaling pathway in patients with schizophrenia. Materials and Methods: In this study, whole blood was obtained from 44 schizophrenic patients and 41 healthy individuals for DNA (patients) and RNA (patients and control) isolation. Samples for CYB mtDNA mutations were amplified by PCR and identified by Sanger DNA sequencing. RT-PCR and 2- increment increment Ct method was used for mRNA expression of PIK3CA, AKT1, and mTOR genes. Results: In schizophrenia patients, m.15326 A > G (43/44), m.15452 C > A (5/44), m.15078 A > G (3/44), m.14872 C > T (3/44) and m.14798 T > C (3/44) was the most common CYB mtDNA mutations. In silico analysis showed that some of the mutations were associated with the harmful, disease-causing or benign character. The mRNA expression of the PIK3CA, AKT1, and mTOR genes in schizophrenia patients was significantly higher than in healthy individuals. There was a significant moderate positive correlation between the PIK3CA and AKT1 genes. In addition, by ROC analysis, PIK3CA, AKT1 and mTOR genes were found to have good diagnostic power in the patient group. ROC analyzes showed that PIK3CA in particular has significant diagnostic value for schizophrenia patients with 80% sensitivity and 63.4% specificity. Conclusion: Both of CYB mtDNA mutations frequency and PIK3CA, AKT1 and mTOR mRNA expression were higher in schizophrenic patients compared to healthy individuals. We believe that studying these mechanisms in
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    Does Lrig1 expression have a relationship with ERBB1 and ERBB2 expression in schizophrenia?
    (Cukurova Univ, Fac Medicine, 2025) Uzuncakmak, Sevgi Karabulut; Ozcan, Halil; Aydin, Pelin; Halici, Zekai
    Purpose: This study aims to investigate Lrig1 expression and to reveal the possible relationship between Lrig1, ERBB1 and ERBB2 in schizophrenia. Materials and Methods: In this study, peripheral blood samples of 70 schizophrenia patients and 60 healthy controls were used. Real Time PCR was applied for Lrig1, ERBB1 and ERBB2 gene expression analysis. Results: The level of Lrig1 mRNA was lower in the patients when compared to healthy controls. Expression levels of ERBB1 and ERBB2 were decreased in the patients versus in the healthy controls. According to the receiver operating characteristic curve analysis, the three genes had the power to discriminate the patients from the ERBB1 and ERBB2 expressions in the patients. in schizophrenia.
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    Evaluation Expression of the Caspase-3 and Caspase-9 Apoptotic Genes in Schizophrenia Patients
    (Korean Coll Neuropsychopharmacology, 2023) Dirican, Ebubekir; Ozcan, Halil; Uzuncakmak, Sevgi Karabulut; Takim, Ugur
    Objective: Apoptosis is programmed cell death that occurs by several pathways. Caspase-3 is induced by active caspase-9 via the intrinsic pathway. The aim of this research was to explore the expression of caspase-3 and caspase-9 in schizophrenia patients and healthy samples. Methods: RNA was isolated from the peripheral blood of 39 schizophrenia patients' and healthy samples. After cDNA synthesis, real time PCR (RT-PCR) was used to analyse caspase-3 and caspase-9 gene expression. The severity of psychopathological symptoms of schizophrenia was evaluated using the Positive and Negative Symptoms Scale for schizophrenia (PANSS) and Clinical Global Impressions (CGI). Results: The expression of caspase-3 and caspase-9 genes was higher in schizophrenia patients than in healthy samples (p = 0.012, p = 0.002, respectively). The increase in caspase-3 gene expression was significant with being male, smoking and with a duration of less than 6 years (p = 0.047, p = 0.049, p = 0.034, respectively). On the other hand, the increase in caspase-9 gene expression was significant in patients who is smoke, have children, and are under 33 years old (p = 0.040, p = 0.043, p = 0.045, respectively). A significant positive correlation was detected between the caspase-3 and caspase-9 gene expression (r = 0.3218, p = 0.049). Conclusion: Our findings indicate that caspase-3 and caspase-9 gene expression may activate cell death mechanisms by intrinsic apoptotic genes. Furthermore, caspase-3 and caspase-9 may play essential roles in different ways in schizophrenia. Hence there is a need to further study the apoptotic mechanism with expanded patient populations.
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    Investigation of cytochrome B mutations, and UCP2 and STC1 gene expressions in patients with bipolar disorder
    (Lippincott Williams & Wilkins, 2025) Uzuncakmak, Sevgi Karabulut; Ozcan, Halil; Dirican, Ebubekir
    Objective The aim herein was to investigate mitochondrial cytochrome B (MT-CYB) mutations in individuals with bipolar disorder. Stanniocalcin-1 (STC1) and uncoupling protein 2 (UCP2) mRNA expressions and their relationship with clinical data and each other were also investigated. Method The blood samples of 100 individuals were included in this study. Real-time PCR was used to evaluate mRNA expressions of STC1 and UCP2. Genetic alterations were investigated via Sanger DNA sequencing. An in silico analysis was performed to reveal the phenotypic effects of MT-CYB mutations. Results In the MT-CYB gene of the bipolar disorder patients, the most seen mutations were the T194A A>G mutation at position 1532, G deletion at position 15498, and C>A L236I mutation at position 15452. Most of the mutations appeared to be neutral or benign. The UCP2 and STC1 mRNA expression levels were significantly higher in the patients than in the healthy controls (P = 0.0124 and P < 0.0001, respectively). The area under the curve values of the receiver operating characteristic curve analysis for UCP2 and STC1 were 0.6631 (P = 0.0123) and 0.8059 (P < 0.0001), respectively. No significant relationship was observed between the gene expressions and the routine laboratory findings. There was a positive correlation between the UCP2 and STC1 mRNA expressions in the bipolar disorder patients (r = 0.03559, P = 0.0306). Conclusion Expression of UCP2 and STC1 may be important parameters in bipolar disorder. MT-CYB mutations may be related to gene expressions. Comprehensive studies on bipolar disorder will help better understand UCP2 and STC1 gene functions. Psychiatr Genet 35: 58-68 Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved.
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    Relation of ATPase6 Mutations and Telomere Length in Schizophrenia Patients
    (Korean Coll Neuropsychopharmacology, 2023) Uzuncakmak, Sevgi Karabulut; Dirican, Ebubekir; Ozcan, Halil; Takim, Ugur
    Objective: Schizophrenia is a serious mental disorder. Mutations in mitochondrial genes can change energy metabolism. Telomere is a tandem sequence at the end of chromosomes. Shorter telomere length has been shown in schizophrenia. The aim of this study was to determine the relationship between ATPase6 gene mutations and telomere length in schizo-phrenia patients.Methods: Blood samples of 34 patients and 34 healthy controls were used. In this study conventional PCR, Sanger sequencing technic and real-time PCR were utilized.Results: Five different mutations (A8860G, A8836, G8697A, C8676T, and A8701G) in the ATPase6 gene were identified in schizophrenia patients. The most seen mutation was A8860G (94%). Telomere length analysis indicated the relation of ATPase6 gene mutations and telomere length variations (p = 0.001). Patients carrying the A8860G mutation had shorter telomere lengths than patients carrying other mutations. Comparing telomere length between schizophrenia pa-tients and healthy controls revealed that the mean telomere length of schizophrenia patients was shorter than healthy controls (p = 0.006). The demographic analysis demonstrated a significant relationship between marital status and telo-mere length (p = 0.011). Besides that, the duration of the illness is another factor that impacts telomere length (p = 0.044). There is no significant relation between telomere length and other clinical and demographic characteristics including education status, age, gender, etc.Conclusion: In conclusion, telomere length and ATPase6 gene mutations have a significant relation. Studies with larger patient populations and investigation of other mitochondrial gene mutations will make the clearer link between telomere length and mitochondrial mutations.