title: Association between the CLOCK gene 3111 T > C polymorphism and an irregular menstrual cycle in Korean adolescents.
abstract: The menstrual cycle is an example of a human infradian rhythm, but an altered sleep-wake cycle or a disrupted circadian rhythm can change the regularity of the menstrual cycle. In this study, we investigated whether an irregular menstrual cycle is associated with polymorphisms in the CLOCK (3111T > C) and/or PER3 (variable number tandem repeat, VNTR) genes, which are known to have an impact on the circadian rhythm. One hundred ninety-seven postmenarchal, adolescent girls from two girls' high schools in Seoul, Korea, were studied. All participants were requested to complete the Perceived Stress Scale (PSS), the State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI) to assess the emotional distress that might cause menstrual irregularity. Every participant donated a blood sample from which DNA was extracted and genotyped for the CLOCK 3111T > C and PER3 VNTR polymorphisms. A significant association was found between the CLOCK 3111T > C genotype and irregular menstrual cycles. Subjects with the 3111T > C genotype had a high risk of an irregular menstrual cycle compared with 3111T/T homozygous subjects (odds ratio [OR] = 2.88; 95% confidence interval [CI]: 1.26-6.55). When multivariate logistic regression analysis was performed to adjust for age, PSS, STAI, BDI and BMI, subjects with the 3111T > C polymorphism showed a significantly increased OR for irregular menstrual cycles (OR = 3.09; 95% CI: 1.32-7.21). There was no significant association between the PER3 VNTR polymorphism and the irregularity of the menstrual cycle (p > 0.05). The results of this study suggest that the CLOCK 3111T > C polymorphism could be an independent risk factor for irregular menstrual cycles, irrespective of psychological distress and endocrine or metabolic conditions, and could be used as a molecular marker for gynecological studies on this aspect.
authors.affiliation: a Department of Obstetrics and Gynecology , Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine , Seoul , South Korea .
authors.forename: Kye-Hyun
authors.initials: KH
authors.lastname: Kim
authors.affiliation: b Department of Psychiatry , Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine , Seoul , South Korea .
authors.forename: Yunsin
authors.initials: Y
authors.lastname: Kim
authors.affiliation: c Department of Psychiatry , Myongji Hospital , Goyang , South Korea , and.
authors.forename: Juwon
authors.initials: J
authors.lastname: Ha
authors.affiliation: b Department of Psychiatry , Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine , Seoul , South Korea .
authors.forename: Dong-Won
authors.initials: DW
authors.lastname: Shin
authors.affiliation: b Department of Psychiatry , Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine , Seoul , South Korea .
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Shin
authors.affiliation: b Department of Psychiatry , Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine , Seoul , South Korea .
authors.forename: Kang-Seob
authors.initials: KS
authors.lastname: Oh
authors.affiliation: d Department of Laboratory Medicine , Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine , Seoul , South Korea.
authors.forename: Hee-Yeon
authors.initials: HY
authors.lastname: Woo
authors.affiliation: b Department of Psychiatry , Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine , Seoul , South Korea .
authors.forename: Se-Won
authors.initials: SW
authors.lastname: Lim
mesh_terms: D000293:Adolescent; D000342:Affective Symptoms / Q000175:diagnosis / Q000503:physiopathology; D056926:CLOCK Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000235:genetics / Q000523:psychology; D008599:Menstruation Disturbances / Q000235:genetics / Q000523:psychology; D056950:Period Circadian Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea
chemical_list: C512644:PER3 protein, human; D056950:Period Circadian Proteins; D056926:CLOCK Proteins; C538943:CLOCK protein, human
keywords: Adolescent; clock genes; irregular menstruation; polymorphism