{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T16:09:29Z","timestamp":1781539769468,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,15]],"date-time":"2024-06-15T00:00:00Z","timestamp":1718409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Projects Coordination Unit of Istanbul University-Cerrahpasa","award":["TTU-2021-35629"],"award-info":[{"award-number":["TTU-2021-35629"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objectives: We aimed to evaluate the DNA methylation levels in perimenopausal and postmenopausal women, measured through Long Interspersed Element-1 (LINE-1) and Alu, and the sleep parameters in relation to the presence of hot flashes (HFs). Methods: This cross-sectional study included 30 peri- or postmenopausal women aged between 45 and 55. The menopausal status was determined according to STRAW + 10 criteria and all participants had a low cardiovascular disease (CVD) risk profile determined by Framingham risk score. The sample was divided into two groups based on the presence or absence of HFs documented in their medical history during their initial visit: Group 1 (n = 15) with HFs present and Group 2 (n = 15) with HFs absent. The patients had polysomnography test and HFs were recorded both by sternal skin conductance and self-report overnight. Genomic DNA was extracted from the women\u2019s blood and methylation status was analyzed by fluorescence-based real-time quantitative PCR. The quantified value of DNA methylation of a target gene was normalized by \u03b2-actin. The primary outcome was the variation in methylation levels of LINE-1 and Alu and sleep parameters according to the presence of HFs. Results: LINE-1 and Alu methylation levels were higher in Group 1 (HFs present), although statistically non-significant. LINE-1 methylation levels were negatively correlated with age. Sleep efficiency was statistically significantly lower for women in Group 1 (HFs present) (74.66% \u00b1 11.16% vs. 82.63% \u00b1 7.31%; p = 0.03). The ratio of duration of awakening to total sleep time was statistically significantly higher in Group 1 (HFs present) (22.38% \u00b1 9.99% vs. 15.07% \u00b1 6.93, p = 0.03). Objectively recorded hot flashes were significantly higher in Group 1 (4.00 \u00b1 3.21 vs. 1.47 \u00b1 1.46, p = 0.03). None of the cases in Group 2 self-reported HF despite objectively recorded HFs during the polysomnography. The rate of hot flash associated with awakening was 41.4% in the whole sample. Conclusions: Women with a history of hot flashes exhibited lower sleep efficiency and higher awakening rates. Although a history of experiencing hot flashes was associated with higher LINE-1 and Alu methylation levels, no statistical significance was found. Further studies are needed to clarify this association. This study was funded by the Scientific Research Projects Coordination Unit of Istanbul University-Cerrahpasa. Project number: TTU-2021-35629.<\/jats:p>","DOI":"10.3390\/jcm13123502","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T06:29:43Z","timestamp":1718605783000},"page":"3502","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["An Evaluation of DNA Methylation Levels and Sleep in Relation to Hot Flashes: A Cross-Sectional Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Ipek Betul","family":"Ozcivit Erkan","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Cerrahpa\u015fa Mah. Kocamustafapa\u015fa Cad. No:34\/E Fatih\/\u0130STANBUL, Istanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2740-7228","authenticated-orcid":false,"given":"Hasan Hakan","family":"Seyisoglu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Cerrahpa\u015fa Mah. Kocamustafapa\u015fa Cad. No:34\/E Fatih\/\u0130STANBUL, Istanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4585-2840","authenticated-orcid":false,"given":"Gulcin","family":"Benbir Senel","sequence":"additional","affiliation":[{"name":"Sleep Disorders Units, Department of Neurology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derya","family":"Karadeniz","sequence":"additional","affiliation":[{"name":"Sleep Disorders Units, Department of Neurology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3960-519X","authenticated-orcid":false,"given":"Filiz","family":"Ozdemir","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysel","family":"Kalayci","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Seven","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7855-1297","authenticated-orcid":false,"given":"Neslihan","family":"Gokmen Inan","sequence":"additional","affiliation":[{"name":"Department of Computer Engineering, College of Engineering, Koc University, Istanbul 34450, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S0140-6736(08)60346-3","article-title":"Menopause","volume":"371","author":"Nelson","year":"2008","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jsbmb.2013.08.010","article-title":"Menopausal Hot Flashes: Mechanisms, Endocrinology, Treatment","volume":"142","author":"Freedman","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1097\/GME.0000000000000586","article-title":"Changes in Heart Rate Variability during Vasomotor Symptoms among Midlife Women","volume":"23","author":"Thurston","year":"2016","journal-title":"Menopause"},{"key":"ref_4","first-page":"979","article-title":"Sleep Disturbance during the Menopausal Transition in a Multi-Ethnic Community Sample of Women","volume":"31","author":"Kravitz","year":"2008","journal-title":"Sleep"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1097\/GME.0000000000001020","article-title":"Association of Vasomotor Symptoms and Sleep Apnea Risk in Midlife Women","volume":"25","author":"Gao","year":"2018","journal-title":"Menopause"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Maniaci, A., Riela, P.M., Iannella, G., Lechien, J.R., La Mantia, I., De Vincentiis, M., Cammaroto, G., Calvo-Henriquez, C., Di Luca, M., and Chiesa Estomba, C. (2023). Machine Learning Identification of Obstructive Sleep Apnea Severity through the Patient Clinical Features: A Retrospective Study. Life, 13.","DOI":"10.3390\/life13030702"},{"key":"ref_7","first-page":"649","article-title":"Effect of 1 Year B and D Vitamin Supplementation on LINE-1 Repetitive Element Methylation in Older Subjects","volume":"51","author":"Geisel","year":"2013","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1210\/clinem\/dgaa081","article-title":"Vasomotor Symptoms and Accelerated Epigenetic Aging in the Women\u2019s Health Initiative (WHI)","volume":"105","author":"Thurston","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"435","DOI":"10.14336\/AD.2017.0810","article-title":"Repetitive Element DNA Methylation Is Associated with Menopausal Age","volume":"9","author":"Lu","year":"2018","journal-title":"Aging Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2478\/bjmg-2020-0001","article-title":"RANKL Is a New Epigenetic Biomarker for the Vasomotor Symptom during Menopause","volume":"23","author":"Kalkan","year":"2020","journal-title":"Balk. J. Med. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1006\/jmbi.1994.0095","article-title":"Ancestral, Mammalian-Wide Subfamilies of LINE-1 Repetitive Sequences","volume":"246","author":"Smit","year":"1995","journal-title":"J. Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1177\/15353702211031247","article-title":"Role of Long Interspersed Nuclear Element-1 in the Regulation of Chromatin Landscapes and Genome Dynamics","volume":"246","author":"Ramos","year":"2021","journal-title":"Exp. Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Deininger, P. (2011). Alu Elements: Know the SINEs. Genome Biol., 12.","DOI":"10.1186\/gb-2011-12-12-236"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1093\/nar\/gnh032","article-title":"A Simple Method for Estimating Global DNA Methylation Using Bisulfite PCR of Repetitive DNA Elements","volume":"32","author":"Yang","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1191\/1358863x02vm418oa","article-title":"DNA Hypomethylation and Methyltransferase Expression in Atherosclerotic Lesions","volume":"7","author":"Hiltunen","year":"2002","journal-title":"Vasc. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1097\/EDE.0b013e3181f20457","article-title":"Ischemic Heart Disease and Stroke in Relation to Blood DNA Methylation","volume":"21","author":"Baccarelli","year":"2010","journal-title":"Epidemiology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ramos, R.B., Fabris, V., Lecke, S.B., Maturana, M.A., and Spritzer, P.M. (2016). Association between Global Leukocyte DNA Methylation and Cardiovascular Risk in Postmenopausal Women. BMC Med. Genet., 17.","DOI":"10.1186\/s12881-016-0335-x"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.4161\/epi.6.10.17728","article-title":"Cardiovascular Disease Risk Factors and DNA Methylation at the LINE-1 Repeat Region in Peripheral Blood from Samoan Islanders","volume":"6","author":"Cash","year":"2011","journal-title":"Epigenetics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/gme.0b013e31824d8f40","article-title":"Executive Summary of the Stages of Reproductive Aging Workshop + 10","volume":"19","author":"Harlow","year":"2012","journal-title":"Menopause"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.cjca.2012.11.032","article-title":"2012 Update of the Canadian Cardiovascular Society Guidelines for the Diagnosis and Treatment of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult","volume":"29","author":"Anderson","year":"2013","journal-title":"Can. J. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1161\/01.CIR.0000053730.47739.3C","article-title":"Clinical Application of C-Reactive Protein for Cardiovascular Disease Detection and Prevention","volume":"107","author":"Ridker","year":"2003","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.2337\/dc12-1577","article-title":"Fasting Glucose Level and the Risk of Incident Atherosclerotic Cardiovascular Diseases","volume":"36","author":"Park","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e023667","DOI":"10.1161\/JAHA.121.023667","article-title":"Body Mass Index and Association With Cardiovascular Outcomes in Patients With Stable Coronary Heart Disease\u2014A STABILITY Substudy","volume":"11","author":"Held","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_24","first-page":"157","article-title":"Cardiovascular Risk in Patients with Subclinical Hypothyroidism","volume":"10","author":"Duntas","year":"2014","journal-title":"Eur. Endocrinol."},{"key":"ref_25","first-page":"282","article-title":"Potential Long-Term Benefit of Home Systolic Blood Pressure Below 125 Mm\u2005Hg for Cardiovascular Risk Reduction: The J-HOP Study Extended","volume":"81","author":"Kario","year":"2023","journal-title":"Hypertension"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1210\/jc.2003-031183","article-title":"Change in Estradiol and Follicle-Stimulating Hormone across the Early Menopausal Transition: Effects of Ethnicity and Age","volume":"89","author":"Randolph","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s13148-015-0154-5","article-title":"The Effects of Long-Term Daily Folic Acid and Vitamin B12 Supplementation on Genome-Wide DNA Methylation in Elderly Subjects","volume":"7","author":"Kok","year":"2015","journal-title":"Clin. Epigenetics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12670","DOI":"10.1038\/s41598-022-15924-x","article-title":"Characterization of Methylation Patterns Associated with Lifestyle Factors and Vitamin D Supplementation in a Healthy Elderly Cohort from Southwest Sweden","volume":"12","author":"Cruz","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_29","first-page":"107","article-title":"Pittsburgh Uyku Kalitesi Indeksinin Gecerligi ve Guvenirligi","volume":"7","author":"Agargun","year":"1996","journal-title":"Turk. Psikiyatr. Derg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11325-007-0145-7","article-title":"Reliability and Validity Studies of the Turkish Version of the Epworth Sleepiness Scale","volume":"12","author":"Izci","year":"2008","journal-title":"Sleep Breath."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6823","DOI":"10.1093\/nar\/gki987","article-title":"Analysis of Repetitive Element DNA Methylation by MethyLight","volume":"33","author":"Weisenberger","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"330","DOI":"10.3748\/wjg.v16.i3.330","article-title":"Aberrant Gene Methylation in the Peritoneal Fluid Is a Risk Factor Predicting Peritoneal Recurrence in Gastric Cancer","volume":"16","author":"Hiraki","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1378\/chest.14-0970","article-title":"International Classification of Sleep Disorders-Third Edition","volume":"146","author":"Sateia","year":"2014","journal-title":"Chest"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.sleep.2016.06.030","article-title":"Demonstration of Sympathetic Dysfunction in Patients with Obstructive Sleep Apnea Syndrome by Measuring Sympathetic Skin Responses from the Neck","volume":"25","author":"Korkmaz","year":"2016","journal-title":"Sleep Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/pst.185","article-title":"Sample Size of 12 per Group Rule of Thumb for a Pilot Study","volume":"4","author":"Julious","year":"2005","journal-title":"Pharm. Stat."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e025969","DOI":"10.1161\/JAHA.122.025969","article-title":"Association of Sleep Duration, Napping, and Sleep Patterns With Risk of Cardiovascular Diseases: A Nationwide Twin Study","volume":"11","author":"Wang","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Terzaghi, M., Toscano, G., and Manni, R. (2020). Sleep Disorders and Cardiovascular Disease. Brain and Heart Dynamics, Springer International Publishing.","DOI":"10.1007\/978-3-030-28008-6_37"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wu, Y., Huang, R., Zhong, X., and Xiao, Y. (2017). Cardiovascular Consequences of Repetitive Arousals over the Entire Sleep Duration. Biomed. Res. Int., 2017.","DOI":"10.1155\/2017\/4213861"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"zsz175","DOI":"10.1093\/sleep\/zsz175","article-title":"Changes in Heart Rate and Blood Pressure during Nocturnal Hot Flashes Associated with and without Awakenings","volume":"42","author":"Baker","year":"2019","journal-title":"Sleep"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1097\/GME.0b013e31828aa344","article-title":"Vagal Withdrawal during Hot Flashes Occurring in Undisturbed Sleep","volume":"20","author":"Colrain","year":"2013","journal-title":"Menopause"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1097\/gme.0b013e3182422973","article-title":"Are Vasomotor Symptoms Associated with Sleep Characteristics among Symptomatic Midlife Women? Comparisons of Self-Report and Objective Measures","volume":"19","author":"Thurston","year":"2012","journal-title":"Menopause"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"100448","DOI":"10.1016\/j.coemr.2023.100448","article-title":"Vasomotor Symptoms and Their Links to Cardiovascular Disease Risk","volume":"30","author":"Carson","year":"2023","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kim, M., Long, T.I., Arakawa, K., Wang, R., Yu, M.C., and Laird, P.W. (2010). DNA Methylation as a Biomarker for Cardiovascular Disease Risk. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009692"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/nrg2005","article-title":"Cancer Epigenomics: DNA Methylomes and Histone-Modification Maps","volume":"8","author":"Esteller","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Jintaridth, P., Tungtrongchitr, R., Preutthipan, S., and Mutirangura, A. (2013). Hypomethylation of Alu Elements in Post-Menopausal Women with Osteoporosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070386"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fncir.2018.00014","article-title":"Sleep Deprivation and the Epigenome","volume":"12","author":"Gaine","year":"2018","journal-title":"Front. Neural Circuits"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"525","DOI":"10.2147\/NSS.S256102","article-title":"Sleep and Methylation of Estrogen Receptor Genes, ESR1 and GPER, in Healthy Middle-Aged and Older Women: Findings from the Women 40+ Healthy Aging Study","volume":"12","author":"Gardini","year":"2020","journal-title":"Nat. Sci. Sleep"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/12\/3502\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:59:11Z","timestamp":1760108351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/12\/3502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,15]]},"references-count":47,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["jcm13123502"],"URL":"https:\/\/doi.org\/10.3390\/jcm13123502","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,15]]}}}