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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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    Role of MIF-173G/C and Mbl2 Codon 54A/B Variants in the Risk of Multiple Myeloma: An Association Study
    (Bentham Science Publ Ltd, 2021) Pehlivan, Mustafa; Nursal, Ayse Feyda; Gundes, Ilknur; Oyaci, Yasemin; Kivanc, Demet; Pehlivan, Sacide
    Background: Multiple myeloma (MM) is a malignant disease manifested by the clonal proliferation of atypical plasma cells. Macrophage inhibitory factor (MIF) is one of the pleiotropic regulators in various biological and cellular processes. Mannose-binding lectin (MBL) is a crucial protein involved in the lectin pathway of the immune system. Objective: We aimed to assess whether variants of MIF and MBL2 genes are associated with MM among a Turkish population. Methods: We analyzed the MIF-173G/C (rs755622) and MBL2 codon 54A/B (rs1800450) variants in 200 patients with MM and 200 healthy control subjects using a polymerase chain reaction (PCR) followed by restriction endonuclease digestion. There was also an evaluation of the patients undergoing autologous stem-cell transplantation (ASCT) for these variants. Results: AA and BB genotypes of MBL2 codon 54A/B increased in the patients as compared to the controls (p=0.008, p=0.001, respectively). The subjects carrying AA and BB genotypes of MBL2 were at high risk of development of susceptibility to MM by 7.377 and 8.812 times, respectively. The distribution of MBL2 codon 54A/B alleles was similar between the groups (p>0.05). There was no statistical difference between the patients and controls in the genotype and allele frequencies of the MIF173G/C variant (p>0.05). The patients undergoing ASCT, MBL2 codon 54A/B AA and BB genotypes also showed association with increased risk for MM (p=0.004, p=0.001, respectively). Conclusion: As far as we know, this is the first report of the study on an association between these variants and MM in our population. Our results indicate that the MBL2 codon 54A/B variant may be associated with susceptibility to MM.
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    The miRNA 196a2 rs11614913 variant has prognostic impact on Turkish patients with multiple myeloma
    (Springernature, 2020) Kirik, Melya Pelin; Pehlivan, Mustafa; Nursal, Ayse Feyda; Oyaci, Yasemin; Pehlivan, Sacide; Serin, Istemi
    Objective Multiple myeloma (MM) arises from malignant plasma cells as a single clone in the bone marrow. Accumulating evidences have reported that there is an association between miR-196a2 (rs11614913) variant and various cancers while there were unverified and inconsistent results in MM. The goal of this study is to investigate the impact of the miR-196a2 variant on clinical findings and susceptibility in MM. Two hundred MM patients (156 patients under transplantation of autologous stem cell) and 200 healthy controls included in this study. Results The statistical analysis showed no significant relationship for allele and frequencies of miR-196a2 genotype between patients and controls (p > 0.05). Log-rank test showed that gender has highly significant impact on both OS and PFS (p = 0.027, p = 0.045). In the univariate analysis, TT genotype (p = 0.022), and CT/TT (p = 0.008) had better OS. In the multivariate analysis, CC/CT-TT were associated with positively OS (p = 0.041). Currently, the most valuable prognostic markers in MM that has clinical implication are genetic abnormalities. It can be concluded from the results that miR-1962a variant is effective in prognosis of the MM. It is believed that these findings will help us understand the molecular basis of disease.
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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.
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    What are the roles of global DNA and APC 2 gene promotor hypermethylation in multiple myeloma?
    (Springer, 2021) Pehlivan, Sacide; Serin, Istemi; Nursal, Ayse Feyda; Oyaci, Yasemin; Gundes, Ilknur; Pehlivan, Mustafa
    Background In today's practice, gene-based approaches come to the fore in the determination of prognosis and treatment preferences of multiple myeloma (MM). DNA methylation is one of the new approach parameters. DNA methylation occurs by the addition of a methyl group to cytosines in CpG dinucleotides. In this study, besides comparing the global DNA and APC 2 gene promotor hypermethylation between our patients with MM and healthy control group, we aimed to demonstrate the effect of hypermethylation on MM treatment responses and survival. Methods and results 38 patients diagnosed with MM between January 2016 and January 2020 and 50 healthy controls were included in the study. The initial hypermethylation of the patients and the healthy control group were statistically analyzed. In addition, the increase in hypermethylation in the MM group before and after the first series of treatments were analyzed within themselves. There is a significant difference between the patients with MM diagnosis and the healthy control group in terms of the initial global hypermethylation (P = 0.001). In patients with MM, hypermethylation was significantly higher. Global hypermethylation in the post-treatment measurements was significantly increased in comparison to the pre-treatment state (P = 0.012). In terms of APC 2 promotor gene-specific hypermethylation, no significant differences were detected between pre- and post-treatment values (P = 0.368). Conclusions This study represents valuable data with the initial global DNA hypermethylation results in the MM patient group and the increase in hypermethylation post-treatment. it will shed light on future studies.