For whom the circadian clock ticks? Investigation of PERIOD and CLOCK gene variants in bipolar disorder

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dc.contributor.authorYegin, Zeynep
dc.contributor.authorSarisoy, Gokhan
dc.contributor.authorErguner Aral, Ayse
dc.contributor.authorKoc, Haydar
dc.date.accessioned2025-03-23T19:35:14Z
dc.date.available2025-03-23T19:35:14Z
dc.date.issued2021
dc.departmentSinop Üniversitesi
dc.description.abstractClock 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.
dc.description.sponsorshipOndokuz Mayis University Scientific Research Projects Coordination Unit [PYO. TIP.1901.19.001]
dc.description.sponsorshipThis work was supported by Ondokuz Mayis University Scientific Research Projects Coordination Unit. Project Number: PYO. TIP.1901.19.001.
dc.identifier.doi10.1080/07420528.2021.1917594
dc.identifier.endpage1119
dc.identifier.issn0742-0528
dc.identifier.issn1525-6073
dc.identifier.issue8
dc.identifier.pmid34112033
dc.identifier.scopus2-s2.0-85107723061
dc.identifier.scopusqualityQ2
dc.identifier.startpage1109
dc.identifier.urihttps://doi.org/10.1080/07420528.2021.1917594
dc.identifier.urihttps://hdl.handle.net/11486/5819
dc.identifier.volume38
dc.identifier.wosWOS:000660327400001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherTaylor & Francis Inc
dc.relation.ispartofChronobiology International
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250323
dc.subjectBipolar disorder
dc.subjectcircadian clock
dc.subjectCLOCK gene
dc.subjectPER2 gene
dc.subjectPER3 gene
dc.titleFor whom the circadian clock ticks? Investigation of PERIOD and CLOCK gene variants in bipolar disorder
dc.typeArticle

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