LINE-1 and Alu Methylation Levels Among Middle Aged Women With Low Cardiovascular Risk Profile in Respect of Menopausal Hot Flashes

Summary

Vasomotor symptoms are the most common symptoms seen during climacterium. The hypoestrogenic state causes dysfunction of hypothalamic preoptic area, a thermoregulatory center. The sympathetic overactivation during the hot flashes is associated with awakening during sleep and have a negative impact on cardiac indexes and vascular reactivity. Therefore, hot flashes are accepted as subclinical cardiovascular risk factor.

The association between the severity of the hot flashes and cardiovascular risk may have an epigenetic background. Recently, methylation changes of DNA was found to be associated with clinical and subclinical cardiovascular disease risk (atherosclerosis and hypertension etc.). A transposable element in the DNA, Long interspersed nuclear elements (LINE-1), was found to be hypomethylated in cases with ischemic heart disease and stroke. Therefore, the expression of repeating elements in the DNA (LINE-1 and ALU) may be considered as a mediator in the ischemic heart disease. Until now, menopausal age, vasomotor symptoms and epigenetic and biological aging have been evaluated. However, the epigenetic impact of severe vasomotor symptoms in postmenopausal women with low cardiovascular disease risk profile has not been evaluated. In this study, we aimed to evaluate the epigenetic basis of cardiovascular disease risk for women with vasomotor symptoms which disturb sleep by assessing the methylation levels of ALU and LINE-1.

Conditions

• Hot Flashes
• Sleep
• Menopause
• Cardiovascular Diseases
• Epigenetics
• DNA Methylation

Interventions

DIAGNOSTIC_TEST

Polysomnography

Polysomnography is performed by 3-channel electroencephalography ((EEG; F4-M1, C4-M1, O2-M1), 2-channel electrooculography (EOG), chin electromyography (EMG), surface EMG recording from tibialis anterior muscles of the right and left leg, body position, oronasal thermal airflow sensor, nasal pressure sensor, thoracic and abdominal respiratory belts for assesing the respiratory effort, electrocardiography (ECG), pulse, recording of respiratory sounds, oxygen saturation and synchronous video recording. The sleep stages are scored by the current criteria of American Academy of Sleep Medicine.

DIAGNOSTIC_TEST

Skin conductance

The sympathetic skin response recordings are performed with a four-channel electromyography apparatus (Nihon-Kohden). They are recorded from both sides of the sternum with the active and reference electrodes placed 2 cm apart from the midline.

GENETIC

ALU and LINE-1 DNA methylation analysis

2 cc peripheric venous blood is drawn from the participants to the test tubes with EDTA. DNA isolation is done by Nucleospin Blood Kit (REF:740951.250, Macherey-Nagel). Epitect Fast DNA Bisulfite Kit (REF:59824, Qiagen) is used to do DNA bisulfite modification. ALU and LINE-1 site specific methylation primer is designed and the methylation patterns are compared between the groups by Epitect Methylight PCR Kit (Cat. No:59496, Qiagen).

DIAGNOSTIC_TEST

The Menopause-Specific Quality of Life Questionnaire (MENQOL)

The Menopause-Specific Quality of Life Questionnaire (MENQOL) is filled by each participant to assess the health related quality of life before the polysomnography test.

DIAGNOSTIC_TEST

Pittsburgh Sleep Quality Index (PSQI)

Pittsburgh Sleep Quality Index (PSQI) is done by each participant to assess the sleep quality and disturbances before thepolysomnography test.

Sponsors & Collaborators

• Scientific Research Project Coordination Unit of Istanbul University-Cerrahpasa

  collaborator UNKNOWN

• Istanbul University - Cerrahpasa

  lead OTHER

Principal Investigators

• Ipek Betul Ozcivit Erkan, MD · Istanbul University - Cerrahpasa

Eligibility

Min Age

45 Years

Max Age

55 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-12-01

Primary Completion

2022-12-01

Completion

2032-03-08

Countries

• Turkey (Türkiye)

Study Locations