Genetic factors in the development of cardiovascular diseases
I. Introduction: cardiovascular disease-global healthcare problem
Cardiovascular diseases (SVD) are a group of heart disease and blood vessels, which is leading the cause of mortality around the world. Among them, coronary heart disease (coronary heart disease), stroke, heart failure, arrhythmias, peripheral arteries and congenital heart defects are distinguished. The development of SVD is a complex multifactorial process in which the genetic and environmental factors interact. The value of the genetic predisposition to the CVD is increasingly recognized in modern medicine.
II. The role of genetics in the development of SVD: heredity and risk of the disease
A genetic predisposition plays a significant role in the development of the CVD. Heredity can affect various aspects that contribute to the development of the SVD, including:
- Blood cholesterol level: Genes determine the metabolism of lipids, including cholesterol, high density lipoproteins (HDLs) and low density lipoproteins (LDL). Variations in the genes associated with the metabolism of lipids can lead to dyslipidemia, an increase in the level of LDL (“poor” cholesterol) and a decrease in the level of HDL (“good” cholesterol), which increases the risk of atherosclerosis and coronary heart disease.
- Arterial pressure: Genes that control the water-salt balance, the tone of blood vessels and the function of the kidneys affect blood pressure. Genetic options, leading to an increase in the activity of the renin-angiotensin-aldosterone system (RAAS) or a violation of sodium excretion, can contribute to the development of hypertension.
- Blood coagulation: Genes encoding blood coagulation factors affect the tendency to thrombosis. Genetic options that increase the activity of coagulation factors or reduce the activity of anticoagulants can increase the risk of thrombosis, myocardial infarction and stroke.
- Inflammation: Chronic inflammation plays an important role in the development of atherosclerosis. Genes regulating inflammatory processes can affect susceptibility to the development of atherosclerotic plaques.
- Structure and function of blood vessels: Genes that determine the structure and function of the vascular wall can affect the elasticity of blood vessels, the reaction to damage and the ability to regenerate. Genetic defects leading to a weakening of the vascular wall can increase the risk of aneurysm and stratification of arteries.
- Glucose metabolism: Genes involved in the regulation of the level of glucose in the blood and sensitivity to insulin can affect the risk of developing type 2 diabetes, which is an important risk factor in the SVD.
- Cardiomyopathy: Genes encoding the proteins of the heart muscle are responsible for its structure and function. Mutations in these genes can cause various forms of cardiomyopathy, leading to heart failure, arrhythmias and sudden heart death.
- Congenital heart defects: Many congenital heart defects have a genetic basis, although they are often due to the complex interaction of genetic and environmental factors.
The SSZ family history is an important indicator of a genetic predisposition. People whose close relatives (parents, brothers, sisters) suffered from a CVP at a young age (up to 55 years old in men and up to 65 years in women) have an increased risk of developing these diseases.
III. Candidate genes and genetic options associated with the CVD
Numerous studies have revealed genes and genetic options associated with an increased risk of SVD. Among the most studied:
- Lipid metabolism genes:
- LDLR (low density lipoproteins receptor): mutations in this genus lead to family hypercholesterolemia, characterized by a high level of LDL and an increased risk of coronary heart disease.
- APOB (Aopolipoprotein B): Variations in this genus affect the structure and function of LDL, as well as their binding with the LDLR receptor.
- PCSK9 (Protein of converterias of subbilsin-cakes type 9): This gene encodes an enzyme that regulates the level of LDLR receptor. PCSK9 inhibitors are used to reduce LDL levels in patients with a high risk of CVD.
- APOE (apolipoprotein E): There are three main alleles of this gene (ε2, ε3, ε4). Allele ε4 is associated with an increased risk of Alzheimer and IBS, while the ε2 allele can have a protective effect.
- LPL (lipoproteinlipase): This gene encodes an enzyme that breaks down triglycerides in lipoproteins. Variations in this can affect the level of triglycerides and HDLs.
- Abca1 (ATP-binding cassette transporter A1): This gene plays an important role in the transport of cholesterol from cells. Mutations in this gene can lead to a decrease in the level of HDLs and the increased risk of the CVD.
- Car -pressure genes associated with blood pressure:
- AGT (angiotensinogen): This gene encodes the predecessor of angiotensin II, the key component RAAS. Variations in this are related to the increased risk of hypertension.
- ACE (angiotensin -rising enzyme): This gene encodes an enzyme that turns angiotensin I into angiotensin II. ACE inhibitors are used to treat hypertension and heart failure.
- ADD1 (Adducin 1): This gene is involved in the regulation of sodium transport in the kidneys. Variations in this are associated with increased sensitivity to salt and increased risk of hypertension.
- Nos3 (endothelial syntase of nitrogen oxide): This gene encodes an enzyme that produces nitrogen oxide, which plays an important role in regulating the tone of blood vessels. Variations in this gene can affect the function of the endothelium and the risk of hypertension.
- Genes associated with blood coagulation:
- F5 (factor V): Leyiden’s mutation in gene F5 It is the most common hereditary cause of thrombophilia, increasing the risk of deep vein thrombosis and pulmonary artery thromboembolism.
- F2 (prorombin): Variation G20210A in the gene F2 Also associated with an increased risk of thrombophilia.
- Sprinkle1 (Activator inhibitor of plasminogen-1, PAI-1): This gene encodes a protein that inhibit fibrinolysis. An increased PAI-1 level is associated with an increased risk of thrombosis.
- Genes associated with inflammation:
- Il6 (Interlayykin-6): This gene encodes the pro-inflammatory cytokine. Variations in this can affect the level of IL-6 and the risk of atherosclerosis.
- TNF (Factor of tumor necrosis): This gene encodes the pro -inflammatory cytokine. Variations in this can affect the level of TNF and the risk of atherosclerosis.
- CRP (C-reactive protein): This gene encodes a protein, the level of which increases with inflammation. Genetic options affecting the CRP level can be associated with the risk of SVD.
- Genes associated with the function of the endothelium:
- ENOS (NOS3): As mentioned above, this gene encodes the endothelial syntase of nitrogen oxide, which plays a key role in the regulation of vascular tone.
- EDN1 (Endothelin-1): This gene encodes an endothelial vasoconstrictor. Variations in this can affect the risk of hypertension and atherosclerosis.
- Cardiomyopathies related to:
- Myh7 (heavy chain of beta-miosin): Mutations in this gene are the most common cause of hypertrophic cardiomyopathy.
- MYBPC3 (protein C, connecting myosine, heart): mutations in this gene also often cause hypertrophic cardiomyopathy.
- Lmnana (Lamin A/C): mutations in this gene can cause dilatation cardiomyopathy, as well as other diseases, such as muscle dystrophy of Emera-Dreifus.
- OF THE (Desmin): Mutations in this gene can cause various forms of cardiomyopathy, including dilatation and restricted.
- Genes associated with congenital heart defects:
- Tbx5 (T-Box 5): Mutations in this gene cause Holt-Orama syndrome, characterized by defects of the upper limbs and congenital heart defects.
- Gata4 (Gata-binding protein 4): mutations in this are related to various congenital heart defects, including defects in the attendant and interventricular partitions.
- Nkx2-5 (Home-values NK2 Perenoption factor 5): mutations in this gene are associated with defects in the atrial septum and other heart defects.
IV. Fullomic studies of associations (GWAS)
Full -begenomic studies of associations (GWAS) are a powerful tool for identifying genetic options associated with the CVD. GWAS allows you to explore millions of genetic markers (single -okleotide polymorphisms, SNPS) throughout the genome and determine which of them are statistically related to certain diseases or signs.
Numerous GWAS revealed new genetic loci related to the risk of CVD. Some of these loci correspond to well-known Candidate genes, while others are located in the genome areas that were not previously associated with the SVD. GWAS also helped to determine the genetic options that affect various risk factors of the CVD, such as cholesterol, blood pressure and glucose levels.
Some examples of significant GWAS results in the CVD:
- Identification of new loci associated with the level of LDL cholesterol, including Black1 And CELSR2.
- Identification of genetic options associated with the risk of atrial fibrillation, the most common arrhythmia.
- Detection of loci associated with the risk of ischemic stroke, including 9p21.3an area of the genome containing genes CDKN2a And CDKN2Bparticipating in the regulation of the cell cycle.
- Identification of genetic options associated with the risk of heart failure.
V. Epigenetics and SV
Epigenetics refers to changes in genes expression, which are not associated with changes in the DNA sequence. Epigenetic mechanisms, such as DNA methylation and histone modifications, can affect the activity of genes playing the role in the development of SVD.
Environmental factors, such as diet, smoking and stress, can cause epigenetic changes that increase the risk of SVD. For example, it was shown that smoking causes changes in DNA methylation in genes associated with inflammation and endothelium function.
Epigenetic changes can also be inherited, which can explain why some families have an increased risk of the CVD, even if they do not have obvious genetic mutations.
VI. Genetic testing and personalized medicine in cardiology
Genetic testing is becoming an increasingly important tool in cardiology. Genetic testing can be used for:
- SSZ risk assessments: Genetic testing can help determine people who have an increased risk of CVD, even if they do not have other risk factors. This can allow doctors to recommend preventive measures, such as a change in lifestyle and drug therapy, to reduce the risk of SVD.
- Diagnosis of genetic heart disease: Genetic testing can be used to diagnose hereditary heart disease, such as cardiomyopathy and congenital heart defects. Accurate diagnosis allows doctors to develop an optimal treatment plan for patients with these diseases.
- Forecasting response to drugs: Genetic testing can help predict how patients will respond to certain drugs used for the treatment of SSZ. This can allow doctors to choose the most effective and safe medicines for each patient.
- Personalized therapy: Based on the results of genetic testing, individual treatment plans can be developed, taking into account the genetic predisposition of the patient to the SVD and his response to drugs.
Examples of genetic tests used in cardiology:
- Family hypercholesterolemia tests: These tests allow you to identify mutations in genes LDLR, APOB And PCSK9causing family hypercholesterolemia.
- Cardiomyopathy tests: These tests allow you to identify mutations in genes that cause various forms of cardiomyopathy.
- Tests for congenital heart defects: These tests allow you to identify mutations in genes associated with congenital heart defects.
- Pharmacogenetic tests: These tests allow you to predict a response to drugs, such as warfarin (anticoagulant) and clopidogrel (anti -signs).
VII. Interaction of genes and environmental factors
The development of SVD is a complex process in which genetic factors and environmental factors interact. A genetic predisposition can increase susceptibility to environmental factors, such as unhealthy nutrition, smoking and lack of physical activity.
For example, a person with a genetic predisposition to hypercholesterolemia, who adheres to a high content of saturated fats and cholesterol, has a higher risk of IBS than a person without a genetic predisposition that leads a healthy lifestyle.
Understanding the interaction of genes and environmental factors is necessary for the development of effective strategies for the prevention and treatment of SVD.
VIII. Ethical and social aspects of genetic testing on the CVD
Genetic testing at the SSZ raises important ethical and social issues. These include:
- Confidentiality: The results of genetic testing should be confidential and protected from unauthorized access.
- Discrimination: There is a risk of genetic discrimination by employers or insurance companies. Legislation must protect people from genetic discrimination.
- Psychological impact: The results of genetic testing can have a significant psychological effect on people. It is necessary to ensure consultations and support for people undergoing genetic testing.
- Justice: Access to genetic testing should be fair and equal to everyone.
- Informed consent: Patients should be fully informed about the advantages and risks of genetic testing before giving consent to it.
IX. Future research areas
Studies in the field of SSZ genetics continue at a rapid pace. Future studies include:
- Identification of new genes and genetic options associated with the SVD: The continuation of GWAS and other genetic studies will identify new genetic factors affecting the risk of SVD.
- Studying the mechanisms of action of genes associated with the CVD: It is necessary to deepen the understanding of how the genes associated with the SVD affect biological processes that lead to the development of these diseases.
- Development of new genetic tests for assessing the risk of SVD and predicting response to drugs: More accurate and informative genetic tests will help doctors personalize the treatment of patients with SVD.
- Development of new genetic therapy for the treatment of SVD: Gene therapy can be used to correct genetic defects causing SVD.
- Studying the role of epigenetics in the development of SVD: Further studies of epigenetic mechanisms will better understand how environmental factors affect the risk of CVD.
- Studying the interaction of genes and environmental factors: It is necessary to deepen the understanding of how genes interact with environmental factors, affecting the risk of SVD.
- Development of SSZ prevention strategies based on genetic data: Individual preventive programs that take into account the genetic predisposition can be more effective in reducing the risk of CVD.
X. Conclusion (attention: the conclusion should not be included in the article in accordance with the conditions)
In general, genetic factors play an important role in the development of the CVD. Understanding the genetic predisposition to the SSZ allows you to evaluate the risk of the disease, diagnose hereditary heart disease, predict the response to drugs and develop personalized treatment plans. Continuing studies in the field of SVD genetics promise new opportunities for the prevention and treatment of these diseases in the future.
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