Associations of Combinations of Single-nucleotide Polymorphisms in Women With Premature Ovarian Failure

Associations of Combinations of Single-nucleotide Polymorphisms and Behavioural Risk Factors With Non-communicable Diseases and Adverse Outcomes in Women With Premature Ovarian Failure

Research objective.

- To study the associations between combinations of single nucleotide polymorphisms and behavioural risk factors with non-communicable diseases and adverse outcomes in women with premature ovarian failure.

Research objectives:

• To study the associations between combinations of single-nucleotide polymorphisms and behavioural risk factors with heart rate disorders and adverse outcomes in women with premature ovarian failure
• Examine the associations between combinations of single nucleotide polymorphisms and behavioural risk factors with stable STIs in women with premature ovarian failure.
• Examine the associations between combinations of single nucleotide polymorphisms and behavioural risk factors with thrombomolia in women with premature ovarian failure
• Study the associations between combinations of single nucleotide polymorphisms and behavioural risk factors and adverse cardiovascular outcomes in women with premature ovarian failure.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Coronary Disease; Arrhythmias, Cardiac; Primary Ovarian Insufficiency; Menopause, Premature; Pulmonary Embolism; Polymorphism, Single Nucleotide
• Intervention / Treatment: Behavioral: Taking a person's venous blood

Detailed Description

Methods of research:

• Questionnaire .
• Clinical examination
• Blood levels of sex hormones
• Blood lipid spectrum
• Coagulogram
• Glycemic profile
• EchoCG
• SMAD
• ECG
• Daily ECG monitoring
• Questionnaire EQ-5D
• Single-nucleotide polymorphisms of genes of the reninangyotensin-aldosterone system group (AGT, ACE), endothelial dysfunction (NOS3, EDN1), thrombosis-associated (ITGB3, ITGA2, FGB, GPIBA, SERPINE PAI1), pro-inflammatory (CRP, IL17A, IL2, IL10 1, IL10 2, TNFα, CRP 4, IL6, TLR2, TLR3, TLR4, TLR6, TLR9) polymorphisms.

Subject of study.

Women under 45 with Premature Ovarian Failure (PED). It is planned to include 615 people in the study. The study will have both prospective and retrospective parts. Patients will be divided into 4 groups:

• Women with OED without cardiovascular disease
• Women with OAI who have cardiovascular disease
• Control group No 1 Women with normal ovarian function without cardiovascular disease.
• Control group 2 Women with normal ovarian function without cardiovascular disease.

The groups will be comparable in number. All data obtained will be calculated for each group separately. A comparative analysis will then be made for all four groups.

Traditional risk factors, existing non-communicable diseases and the quality of life of patients will be identified using standard research methods.

The selected polymorphism groups are associated with various pathological processes leading to unfavourable cardiovascular outcomes. Their role has not been assessed in patients with premature ovarian failure.

The power of the study was calculated based on the expected number of adverse outcomes.

The division of patients into groups is related to the need to compare and evaluate unfavourable outcomes and non-communicable diseases in patients in order to create a risk scale.

• Study Type: Interventional
• Enrollment (Actual): 238
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Ryazan Region
    • Ryazan, Ryazan Region, Russian Federation, 390044
      • Sergey Vladimirovich Lopukhov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 45 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• women under 45 years old
• presence of premature ovarian insufficiency in the medical history

Exclusion Criteria:

• male gender
• age over 45 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Study of single-nucleotide polymorphisms in women diagnosed with premature ovarian failure; Study of genes affecting single nucleotide polymorphisms: Reninangiotensin-aldosterone system (AGT, ACE), endothelial dysfunction (NOS3, EDN1), thrombosis-associated (ITGB3, ITGA2, FGB, GPIBA, SERPINE PAI1), proinflammatory (CRP, IL17A, IL2, IL10 1, IL10 2, TNFα, CRP 4, IL6, TLR2, TLR3, TLR4, TLR6, TLR9) in the study group of women diagnosed with premature ovarian failure.	Behavioral: Taking a person's venous blood; Collection of 5 ml of the patient's venous blood, carried out according to standard rules.
Active Comparator: Study of single-nucleotide polymorphisms in a control group of healthy women; Study of genes affecting single nucleotide polymorphisms: Reninangiotensin-aldosterone system (AGT, ACE), endothelial dysfunction (NOS3, EDN1), thrombosis-associated (ITGB3, ITGA2, FGB, GPIBA, SERPINE PAI1), pro-inflammatory (CRP, IL17A, IL2, IL10 1, IL10 2, TNFα, CRP 4, IL6, TLR2, TLR3, TLR4, TLR6, TLR9) in a control group of healthy women .	Behavioral: Taking a person's venous blood; Collection of 5 ml of the patient's venous blood, carried out according to standard rules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age (years)	Patient age in years	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Menarche (years)	Age of onset of menarche expressed in years	2 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy (number)	Number of pregnancies in history	2 year
Childbirth (number)	Number of pregnancies that ended in childbirth	2 year
Menopause (yes/no)	Current presence or absence of menopause	2 year
Surgical removal of both ovaries (yes/no)	History of surgery involving bilateral removal of both ovaries	2 year
Presence of amenorrhoea (at least 4 months) (yes/no)	A history of amenorrhoea for at least 4 months	2 year
Follicle stimulating hormone (FSH) level (mMed/ml)	Blood follicle-stimulating hormone content expressed in mMED/ml	2 year
Age at menopause (years)	Age of onset of menopause	2 year
Length of post-menopause (years)	How many years a person has been in the post-menopausal phase	2 year
Taking oral contraceptives (yes/no)	Whether the patient is continuously taking oral contraceptives	2 year
Taking hormone replacement therapy (HRT) (yes/no)	Whether the patient is taking regular hormone replacement therapy	2 year
Length of time on hormone replacement therapy (years)	How long the patient has been on hormone replacement therapy	2 year
Smoking status (yes/no)	Does the patient use nicotine-containing substances on a regular basis	2 year
Number of cigarettes smoked per day (number)	How many cigarettes the patient smokes per day on average	2 year
Smoking experience (years)	Number of years of active nicotine use by the patient	2 year
Smoking index (points)	Calculated as the number of cigarettes smoked per day and years of smoking experience divided by 20.	2 year
Height (cm)	Patient's height measured in centimetres	2 year
Weight (kg)	Patient weight measured in kilograms	2 year
BMI (kg/m2)	Body mass index is determined using the standard method	2 year
Waist circumference (cm)	Waist circumference measured in centimetres using the standard method	2 year
Hip circumference (cm)	Hip circumference measured in centimetres using the standard method	2 year
Waist circumference to hip circumference ratio (WHR) (number)	Waist circumference to hip circumference index calculated using the standard method	2 year
Secondary education (yes/no)	Does the patient have a high school education	2 year
Secondary vocational education (yes/no)	Does the patient have a secondary vocational education	2 year
Higher education (yes/no)	Does the patient have a university degree	2 year
Systolic blood pressure (mmHg)	Systolic blood pressure measured using the standard method	2 year
Diastolic blood pressure (mmHg)	Diastolic blood pressure measured using the standard method	2 year
Heart rate (number)	Heart rate measured using the standard method	2 year
Radial artery pulse (beats per minute).	Radial artery pulse measured using standard methods	2 year
Arterial hypertension (yes/no)	History of arterial hypertension	2 year
Ultrasound examination of the heart	Ultrasound examination of the heart carried out using standard methods to detect cardiac abnormalities	2 year
Total cholesterol (mmol/l)	Total cholesterol measured by standard methods	2 year
High-density lipoproteins (HDL) (mmol/l)	High-density lipoproteins measured by standard methods	2 year
Low density lipoproteins LDL (mmol/l)	Low density lipoproteins measured by standard methods	2 year
Triglycerides (mmol/l)	Triglycerides measured by standard methods	2 year
Cholesterol/HDL ratio (number)	Calculated using the standard method	2 year
Blood glucose level (mmol/l)	Amount of glucose in the blood measured by the standard method	2 year
Glycated haemoglobin (HbA1c), (percent %)	Glycated haemoglobin measured by standard methods	2 year
Diabetes mellitus (yes/no)	Indication of diabetes mellitus in the patient's medical history	2 year
Taking antihypertensive medication (yes/no)	Indication of antihypertensive medication in the patient's medical history	2 year
Taking hypolipidemic medicines (yes/no)	Use of hypolipidemic drugs in a patient's history	2 year
Metabolic syndrome (yes/no)	Indicating a history of metabolic syndrome	2 year
Presence of post-menopausal diagnosis: arrhythmia or other rhythm disturbances (yes/no)	Post-menopausal diagnosis of arrhythmia or other rhythm disturbances based on medical history	2 year
Presence of a post-menopausal diagnosis of coronary heart disease (yes/no)	Presence of post-menopausal diagnosis of coronary heart disease according to medical history	2 year
Presence of a post-menopausal diagnosis of myocardial infarction (yes/no)	Post-menopausal diagnosis of myocardial infarction based on medical history	2 year
Presence of post-menopausal diagnosis: thromboembolism (yes/no)	Post-menopausal diagnosis of thromboembolism based on medical history	2 year
Post-menopausal diagnosis of varicose veins in the lower limbs (yes/no)	Post-menopausal diagnosis of varicose veins in the lower limbs based on medical history	2 year
Presence of a post-menopausal diagnosis: Acute cerebral haemorrhage (yes/no)	Post-menopausal diagnosis of acute cerebral haemorrhage on medical history	2 year
Deaths from cardiovascular disease in the post-menopausal period (yes/no)	Cardiovascular deaths in the post-menopausal period based on the pathologist's medical history report	2 year
A history of cancer (yes/no)	Determined on the basis of the medical history	2 year
AGT gene Met235Thr, rs699 polymorphism	Identification of Met235Thr/rs699 polymorphisms in the AGT gene	2 year
ACE gene Alu Ins/Del I>D, rs4646994 polymorphism	Identification of Alu Ins/Del I>D, rs4646994 polymorphisms in the ACE gene	2 year
NOS3 gene C786T, rs2070744 polymorphism	Identification of C786T, rs2070744 polymorphisms in the NOS3 gene	2 year
EDN1 gene Lys198Asn, rs5370 polymorphism	Identification of Lys198Asn, rs5370 polymorphisms in the EDN1 gene	2 year
ITGB3 gene Leu33Pro, rs5918 polymorphism	Identification of Leu33Pro, rs5918 polymorphisms in the ITGB3 gene	2 year
ITGA2 gene C807T, rs1126643 polymorphism	Identification of C807T, rs1126643 polymorphisms in the ITGA2 gene	2 year
FGB gene 455G-A, rs1800790 polymorphism	Identification of 455G-A, rs1800790 polymorphisms in the FGB gene	2 year
SERPINE (PAI) 1 gene 675 5G/4G, rs1799768 polymorphism	Identification of 675 5G/4G, rs1799768 polymorphisms in the SERPINE (PAI) 1 gene	2 year
CRP gene C3872T, rs1205 polymorphism	Identification of C3872T, rs1205 polymorphisms in the CRP gene	2 year
IL17A gene G-197A, rs2275913 polymorphism	Identification of G-197A, rs2275913 polymorphisms in the IL17A gene	2 year
IL2 gene T-330G, rs2069762 polymorphism	Identification of T-330G, rs2069762 polymorphisms in the IL2 gene	2 year
IL10 gene C-592A, rs1800872 polymorphism	Identification of C-592A, rs1800872 polymorphisms in the IL10 gene	2 year
TNF gene G-308A, rs1800629 polymorphism	Identification of G-308A, rs1800629 polymorphisms in the TNF gene	2 year
CRP gene A-717G, rs2794521 polymorphism	Identification of A-717G, rs2794521 polymorphisms in the CRP gene	2 year
IL6 gene C-174G, rs1800795 polymorphism	Identification of C-174G, rs1800795 polymorphisms in the IL6 gene	2 year
TLR2 gene Arg753Gln, rs5743708 polymorphism	Identification of Arg753Gln, rs5743708 polymorphisms in the TLR2 gene	2 year
TLR3 gene Phe412Leu, rs3775291 polymorphism	Identification of Phe412Leu, rs3775291 polymorphisms in the TLR3 gene	2 year
TLR4 gene Asp299Gly, rs4986790 polymorphism	Identification of Asp299Gly, rs4986790 polymorphisms in the TLR4 gene	2 year
TLR6 gene Ser249Pro, rs5743810 polymorphism	Identification of Ser249Pro, rs5743810 polymorphisms in the TLR6 gene	2 year
TLR9 gene T-1237C, rs5743836 polymorphism	Identification of T-1237C, rs5743836 polymorphisms in the TLR9 gene	2 year

Collaborators and Investigators

• Sponsor: Ryazan State Medical University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): June 3, 2022
• Study Completion (Actual): December 12, 2023

Study Registration Dates

• First Submitted: November 27, 2020
• First Submitted That Met QC Criteria: June 28, 2021
• First Posted (Actual): June 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: cardiovascular disease; single nucleotide polymorphisms; pulmonary embolism; coronary heart disease; cardiovascular outcomes; premature ovarian failure; cardiac arrhythmias; hypoestrogenism; artificial menopause; chronic non-infectious disease; heart rhythm disturbances
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Embolism and Thrombosis; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Coronary Disease; Cardiovascular Diseases; Embolism; Premature Birth; Arrhythmias, Cardiac; Primary Ovarian Insufficiency; Menopause, Premature; Pulmonary Embolism
• Other Study ID Numbers: 20-315-90017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes