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    Global and glucocorticoid receptor gene-specific (NR3C1) DNA methylation analysis in patients with cannabinoid or synthetic cannabinoid use disorder
    (Elsevier Ireland Ltd, 2021) Pehlivan, Sacide; Aytac, Hasan Mervan; Aydin, Pinar Cetinay; Nursal, Ayse Feyda; Pehlivan, Mustafa
    This study investigates the relationship between cannabinoid use disorder (CUD) or synthetic cannabinoid use disorder (SCUD) and the global methylation, methylation of NR3C1 gene promotor, and NR3C1 BclI poly-morphism, considering clinical parameters. Based on the DSM-5 criteria, 172 SCUD patients? and 44 CUD pa-tients? diagnoses were confirmed with a positive urine test; 88 healthy volunteers were also included in the study. Global DNA methylation was measured using a 5-methylcytosine (5-mC) DNA ELISA Kit. Methylation-specific PCR was used to identify the methylation of the NR3C1 gene. The analysis of the BclI polymorphism of the NR3C1 gene was evaluated by using the PCR-RFLP. Our results demonstrated that the mean of 5-mC percentages of SCUD patients differed significantly from those of the control group. When comparing NR3C1 gene methyl-ation and clinical parameters due to NR3C1 genotype distribution in patients, the genotype distribution was significantly different between the groups, due to the former polysubstance abuse. Additionally, there was a significantly positive correlation between the 5-mC percentages of SCUD patients and the reported durations of their disorders. In summary, whereas global DNA methylation may be associated with SCUD, the methylation of the NR3C1 gene and NR3C1 BclI polymorphism were not related to CUD or SCUD.
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    Investigating the eNOS and IFN-gamma Gene Variants Susceptible to Bipolar Disorder or Schizophrenia in a Turkish Cohort
    (Turkish Assoc Psychopharmacology, 2020) Pehlivan, Sacide; Aytac, Hasan Mervan; Ciftci, Hayriye Senturk; Oyaci, Yasemin; Pehlivan, Mustafa; Nursal, Ayse Feyda
    Background: Schizophrenia (Sch) and bipolar disorder (BD) are debilitating chronic psychiatric disorders that are both etiologically and clinically heterogeneous. According to the gathered evidence, multiple mental disorders are accompanied by inflammation. Interferon-gamma (IFN-gamma), as a regulatory cytokine, is involved in the immune response as a proinflammatory mediator. Several critical physiological functions are regulated and governed by nitric oxide (NO) in the central nervous system. This study aimed to investigate the association between IFN-gamma +874T/A and eNOS 894G/T variants and Sch or BD susceptibility. Methods: Blood samples were collected from patients and healthy subjects. IFN-gamma +874T/A and eNOS 894G/T variants were genotyped with the PCR-RFLP. We evaluated the patients with some clinical parameters (the duration of the disorder, age of onset, number of hospitalizations, family history, tobacco smoking or drug, alcohol usage). Statistical analyses were performed using the SPSS version. Results: When the genotype distributions and allele frequencies of the IFN-gamma +874T/A and eNOS 894G/T in the patients diagnosed with Sch or BD were compared with the control group, there were not found to be significant differences between the groups. When comparing IFN-gamma +874T/A and eNOS 894G/T genotype distributions and allele frequencies of Sch or BD patients due to clinical parameters, the genotype distribution of IFN-gamma +874T/A in BD patients was significantly different between the groups due to the presence of tobacco smoking (OR: 0.217, 95%Cl: 0.054-0.878; p = 0.032). Conclusions: To the best of our knowledge, this is the first study that examines the association between the IFN-gamma and eNOS gene variants and Sch or BD in a Turkish population. Although IFN-gamma +874T/A and eNOS 894G/T variants are not considered as candidate genes for Sch or BD, the results indicated that the BD patients carrying IFN-gamma +874T/A AA genotype were less susceptible to tobacco smoking in a Turkish population.
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    TNF-alpha-308 G/A variant may be associated with bipolar disorder in a Turkish population
    (Univ Sao Paulo, Inst Psiquiatria, 2020) Nursal, Ayse Feyda; Aytac, Hasan Mervan; Ciftci, Hayriye Senturk; Yazar, Menekse Sila; Oyaci, Yasemin; Pehlivan, Mustafa; Pehlivan, Sacide
    Background: Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory multifunctional cytokine produced by macrophages. A dysregulation of the immune system contribute to the pathogenesis of bipolar disorder (BD). In this study, we aimed to investigate the relationship between the TNF-alpha gene -308G/A promoter variant and the risk of BD. Methods: A total of 104 BD patients and 94 healthy controls were enrolled in the study. Genomic DNA was isolated and TNF-alpha-308G/A variant was analyzed using PCR-RFLP method. Results: TNF-alpha-308G/A variant GG genotype and G allele were more prevalent in BD patients compared to the controls (p = 0.002 and p = 0.017, respectively). The patients carrying GG genotype had a 5.927-fold higher risk of developing BD. Then, we divided patients into two groups as smokers and non-smokers. TNF-alpha-308G/A variant GA genotype was higher in non-smoker BD patients than smoker patients (p = 0.027). We found that TNF-alpha-308G/A AA genotype and A allele increased in smoker patients compared to non-smoker patients (p = 0.008, p = 0.002, respectively). Discussion: Our results provided evidence that TNF-alpha-308G/A variant may contribute to development of BD in a Turkish cohort. In addition, this variant plays a relevant role in the smoker status of BD.