An Evaluation of DNA Methylation Levels and Sleep in Relation to Hot Flashes: A Cross-Sectional Study

Abstract

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’s 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 β-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% ± 11.16% vs. 82.63% ± 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% ± 9.99% vs. 15.07% ± 6.93, p = 0.03). Objectively recorded hot flashes were significantly higher in Group 1 (4.00 ± 3.21 vs. 1.47 ± 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.

Keywords

• hot flashes
• epigenetics
• DNA methylation
• LINE-1 methylation
• ALU methylation
• sleep