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Öğe For whom the circadian clock ticks? Investigation of PERIOD and CLOCK gene variants in bipolar disorder(Taylor & Francis Inc, 2021) Yegin, Zeynep; Sarisoy, Gokhan; Erguner Aral, Ayse; Koc, HaydarClock genes play significant roles in the regulation of circadian rhythms, which are thought to be involved in the pathophysiology of neurodegenerative and psychiatric diseases. We aimed to investigate the association of five gene polymorphisms (PER3 VNTR (rs57875989), PER2 rs2304672, CLOCK rs1801260, CLOCK rs10462028, CLOCK rs11932595) with PCR-based methods as potential risk factors in bipolar disorder (BD). We used a multiple testing methodology in BD patients (n = 121) and healthy control individuals (n = 121) of Turkish descent to analyze the effects of these gene variants both as risk factors for the disorder and for the evaluation of these variants in the patient group with multiple subscales. We evaluated the circadian rhythm disturbances and seasonal variations in mood and behavior in BD patients using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) and Seasonal Pattern Assessment Questionnaire (SPAQ) to enlighten the possible links between these scores and the studied circadian gene variants. The results of our study revealed significant associations: PER3 VNTR (rs57875989) 5/5 repeat genotype displayed a protective effect against BD when compared with 4/4 repeat genotype. Moreover, patients with PER3 VNTR 5/5 repeat genotype displayed a higher ratio of hypomania. PER2 rs2304672 G allele frequency increased the risk for BD. There was no association in terms of genotype/allele frequency comparisons between patients and controls for CLOCK gene variants. However, significant associations were found in patients in terms of clinical and behavioral patterns such as mean age at disease onset and BRIAN total scores enabling some risk stratifications for patients. Our results indicate the significance of circadian gene variants in BD, which need to be confirmed in different studies with larger samples. Thus, the possible endophenotypes of BD can be enlightened and advanced chronotherapeutics approaches can be manipulated in the future for clinical benefit.Öğe Investigation of the functional vesicular monoamine transporter 1 (VMAT1/SLC18A1) Thr136Ile gene variant in bipolar disorder(Sociedad Espanola de Psiquiatria Biologica (SEPB), 2022) Yegin, Zeynep; Sarisoy, Gokhan; Erguner Aral, Ayse; Koc, HaydarBackground and objectives: Bipolar disorder (BD) is an episodic and recurrent mood disturbance ranging from mania to severe depression. Because of the heterogeneity of psychiatric disorders, enlightening the possible molecular risk drivers is crucial. Vesicular monoamine transporter 1 (VMAT1) is an important candidate gene to study the underlying molecular mechanisms in BD pathogenesis since it has a significant role in the packaging of monoaminergic neurotransmitters into presynaptic storage vesicles. The aim of this study was to ascertain whether functional and evolutionarily important variant of VMAT1 gene (Thr136Ile (rs1390938)) would affect the susceptibility of the individuals to BD in a Turkish population. Method: One hundred twenty BD patients and one hundred one healthy control individuals were recruited for the study. Samples were genotyped using PCR-RFLP method to detect VMAT1 gene variant (Thr136Ile (rs1390938)). Results: Contrary to our expectations, VMAT1 Thr136Ile (rs1390938) gene variant was not associated with BD in our population. There was also no relationship between VMAT1 genotypes and some clinically significant parameters in BD patients. Conclusion: Our data showed no association between VMAT1 Thr136Ile (rs1390938) and BD in Turkish population. We strongly recommend the analysis of this variant in other populations to draw a precise conclusion about the role of this variant in bipolar disorder. Further large-scale research for the other variants of VMAT1 is also required to clarify the strong hypothesis focused on VMAT1 variants in the development of neuropsychiatric disorders. © 2022Öğe Role of miRNA Gene Variants (miR-22 and miR-155) as the Factors Affecting Susceptibility to Panic Disorder(Korean Coll Neuropsychopharmacology, 2024) Yegin, Zeynep; Sarisoy, Gokhan; Uzun, Ahmet; Koc, HaydarObjective: Variants within genes encoding microRNAs (miRNAs) may alter the expression of both miRNAs and their target genes, thus contributing to the etiology of psychiatric disorders. The involvement of miRNAs in neuronal differentiation and synaptic plasticity supported this hypothesis. We aimed to investigate the links between miR-155 rs767649/miR-22 rs8076112 and the risk of panic disorder (PD) in a sample of Turkish population. Methods: In this experimental study, 134 PD patients and 140 healthy controls were recruited. Genotyping was carried out using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. To evaluate PD phenotypes, Panic Disorder Severity Scale (PDSS) was also administered to patients to clarify possible associations between the scale and risk variants analyzed. Results: The genotype analysis of miR-155 rs767649 did not show an association with PD risk and it was not related to the disease severity. For miR-22 rs8076112 variant, a statistically significant association was determined; CC genotypes were lower in patients compared to controls. Logistic regression analysis proved the highly protective effect (80.4%) of CC genotype against PD (p = 0.041; OR = 0.196, 95% CI = 0.041-0.934). Though its significance in disease liability, miR-22 rs8076112 was not associated with the disease severity. Conclusion: Our findings firstly report the combined analysis of miR-155 rs767649 and miR-22 rs8076112 in PD in terms of both disease susceptibility and severity. These findings await replication in independent cohorts with enrichment of other miRNA gene variants. Thus, certain miRNAs and their target genes involved in the etiology and phenotypes of PD could be enlightened.Öğe The frequency of retrotransposon human endogenous retrovirus-K113 and a preliminary analysis of some microbial clues in bipolar disorder(Future Medicine Ltd, 2020) Yegin, Zeynep; Avsar, Cumhur; Sarisoy, GokhanAim: The aim of our study was to investigate whether the retrotransposon human endogenous retrovirus (HERV)-K113 could be related with bipolar disorder or not. As a second and a preliminary aim, we also conducted bacterial screening in whole blood in a limited number of samples. Patients & methods: Three separate PCR reactions including the preintegration sites and sites within the viral sequences were performed for HERV-K113 detection. Bacterial screening was performed with SSCP/sequencing analysis. Results & conclusion: No difference was observed in terms of the frequency of retrotransposon HERV-K113 in Turkish bipolar disorder patients and healthy controls. SSCP/sequencing and alignment analysis for bacterial screening reflected the possible presence of different bacteria. We strongly recommend the broadened retrotransposon and microbial diversity analyses in bipolar disorder for future studies.