Genetic aspects of cardiovascular diseases

Genetic aspects of cardiovascular diseases

1. Cardiovascular diseases (SVD): Review and scale of the problem

Cardiovascular diseases (SSZ) are a group of diseases that affect the heart and blood vessels. This is the leading cause of mortality around the world, which accounts for about 31% of all deaths. SSZ includes a wide range of states, such as:

• Coronial heart disease (CPS) or coronary heart disease (CBS): this is the most common type of SVD, characterized by a decrease in the blood supply to the heart muscle, often due to atherosclerosis (deposits of plaques in the arteries).
• Stroke: It occurs when the blood supply to the brain is interrupted, which leads to damage to the brain. It can be caused by the blockage of the artery (ischemic stroke) or the rupture of the blood vessel (hemorrhagic stroke).
• Heart failure: a state in which the heart cannot pump blood in sufficient quantities to meet the needs of the body.
• Arrhythmia: heart rhythm disturbances that can be too fast (tachycardia), too slow (bradycardia) or irregular.
• Congenital heart defects: malformations of the heart present at birth.
• Disease of peripheral arteries (BPA): narrowing of arteries that supply the limbs, most often legs.
• Rheumatic heart disease: damage to heart valves caused by rheumatic fever, complication of streptococcal throat infection.
• Cardiomyopathy: the disease of the heart muscle, which can lead to heart failure.
• Aortic diseases: states that affect the aorta, the main artery emerging from the heart, including aneurysms (expansion) and stratification (gaps of the aortic wall).

The traditional risk factors of the SSZ are well known and include:

• High blood pressure (hypertension)
• High blood cholesterol (hyperlipidemia)
• Smoking
• Diabetes
• Obesity
• Insufficient physical activity
• Improper nutrition
• Age
• Paul (men, as a rule, are at greater risk than women before menopause)
• Family history of SSZ

However, it becomes more and more obvious that genetics plays a significant role in the development of the SVD, regardless of the traditional risk factors. Genetic factors can affect a person’s susceptibility to the SVD, the severity of the disease and the reaction to treatment. Understanding the genetic foundation of the SVD is crucial for the development of new strategies for prevention, diagnosis and treatment.

2. The role of genetics in cardiovascular diseases

The heredity of the SVD varies depending on the specific disease and the population under study. In general, coronary heart disease is estimated as heredity from 40% to 60%, which means that genetic factors make a significant contribution to the risk of this disease. Other SVDs, such as cardiomyopathy and some congenital heart defects, have much higher heredity, often approaching 80% or even 100% in some cases.

The genetic impact on the CVD can be classified into several wide categories:

• Monogenic diseases: These diseases are caused by mutations in one gene and usually have a high degree of penetrance, that is, people who have inherited the mutation will most likely develop the disease. Examples of monogenic SSZs include family hypercholesterolemia (caused by mutations in LDLR, APOB or PCSK9), hypertrophic cardiomyopathy (caused by mutations encoding sarcomer proteins) and marfan syndrome (caused by mutations in the FBN1 gene).
• Polygenic diseases: These diseases are caused by the interaction of many genes, each of which makes a small contribution to the risk of the disease. The influence of each individual gene can be small, but the combined effect of many genes can significantly affect a person’s susceptibility to the SVD. IBS, hypertension and stroke are examples of polygenic SSZs.
• The interaction of genes and the environment: In the development of the SVD, complex interaction between genes and environmental factors is often involved. For example, a person genetically predisposed to hypertension can be more susceptible to increased blood pressure when using a diet with a high salt content. Similarly, the genetic predisposition to coronary heart disease can aggravate smoking or insufficient physical activity.
• Epigenetic changes: Epigenetics refers to changes in genes expression, which are not associated with changes in the sequence of DNA itself. Epigenetic changes can affect the risk of SVD, modulating the activity of genes involved in the cardiovascular function. Environmental factors, such as diet, stress and the effects of toxins, can cause epigenetic changes that can be transmitted from generation to generation.

3. Methods of genetic research of the SSZ

Over the past few decades, significant progress has been achieved in the identification of genes and genetic options associated with the SVD. Various methods of genetic research are used to study the genetic basis of the SVD:

• Studies of the genealogy (Family Studies): Studies of pedigree include analysis of families with high prevalence of SVDs to identify inheritance patterns and cartridge genes. These studies can be especially useful for identifying genes that cause monogenic SSZs.
• Linkage Studies studies: Relations of the connection are used to determine the location of the genes responsible for the SVD by analyzing the joint inheritance of genetic markers (for example, microsatellites) and diseases in families. If the genetic marker is often inherited with the disease, this suggests that the gene gene is probably near this marker on the chromosome.
• Fullomic associative studies (GWAS): GWAS is a powerful method used to identify genetic options associated with the SVA, by scanning the genome of thousands of people to search for DNA options (single -okleotide polymorphisms or SNPS), which are more common in people with people without illness. GWAS revealed hundreds of genetic loci associated with various SVDs, including coronary heart disease, hypertension and stroke.
• Exom sequencing (EXOME SEQUENCING): Exom sequencing is a sequencing method that is aimed only at the exons of the genome, that is, on parts of genes that encode proteins. EXTOMS sequencing is an economically effective way to identify rare genetic options that can cause SVD.
• Sequencing of the entire genome (Whole-Genome Sequencing): Sequencing of the entire genome includes the determination of the entire sequence of human DNA, including both encoding and non -leading areas of the genome. Sequencing of the entire genome is the most complete method of genetic analysis and can identify all types of genetic options, including SNPS, deletions, inserts and structural options.
• Transcription analysis (Transcriptome Analysis): Transcript analysis, for example, RNA-EQ, is used to measure genes expression in various tissues and cells. Transcript analysis can identify genes whose expression changes at the CVD, and can provide information about the molecular mechanisms underlying the disease.
• Proteom analysis (Proteomics): Proteom analysis is used to identify and quantitative assessment of proteins in biological samples. Proteom analysis can detect proteins whose levels change at the SVD, and can provide information about the biological pathways involved in the disease.
• Metabolon analysis (Metabolomics): Metabolon analysis is used to measure the levels of small molecules (metabolites) in biological samples. Metabolonal analysis can identify metabolic pathways that are violated with the CVD, and can provide information about the pathophysiology of the disease.
• Epigenomic studies (Epigenomic Studies): Epigenomic studies are used to study epigenetic changes, such as DNA methylation and histone modification, which affect the expression of genes. Epigenomic studies can reveal the epigenetic mechanisms involved in the development of SVD.
• Analysis of Mendelian randomization (Mendelian Randomization): Analysis of Mendelian randomization uses genetic options as instrumental variables to assess the causal relationship between the risk factor (for example, cholesterol) and SVD. This method can help determine whether the observed associations between the risk factor and the CVD are causable or simply correlation.

4. Genes and genetic variants associated with the CVD

Numerous genes and genetic options were associated with various SVDs. Here are some examples:

• Family hypercholesterolemia: Caused by mutations in genes LDLR, APOB or PCSK9. These genes play a role in the metabolism of LDL cholesterol (low density lipoproteins). Mutations in these genes lead to an increased level of LDL cholesterol in the blood, which significantly increases the risk of coronary heart disease.
• Hypertrophic cardiomyopathy: Caused by mutations in genes encoding sarcomer proteins, such as Myh7, MYBPC3, TPM1 And ACTC1. These mutations lead to a thickening of the heart muscle, which can lead to heart failure, arrhythmias and sudden heart death.
• Marfan syndrome: Called by mutations in the gene FBN1which encodes fibrillin-1, protein, which is the main component of the extracellular matrix. Mutations in FBN1 They lead to problems with connective tissue, which can cause heart problems, including aortic aneurysm and mitral valve prolapse.
• Dilata Cardiomyopathy: Can be caused by mutations in various genes, including Lmnana, OF THE, TTN And SCN5A. These mutations lead to an increase in the size of the heart chambers and a decrease in the contractility of the heart muscle, which leads to heart failure.
• Lengered QT interval syndrome: Caused by mutations in genes encoding the ion channels of the heart, such as KCNQ1, KCNH2 And SCN5A. These mutations lead to lengthening the QT interval on the ECG, which increases the risk of dangerous arrhythmias.
• Catecholamine-dependent polymorphic ventricular tachycardia (CPZT): Caused by mutations in genes Ryr2 or CASQ2. These mutations lead to arrhythmias caused by physical exercises or stress.
• Ichemic heart disease: GWAS revealed hundreds of genetic loci associated with coronary heart disease. Some of the most famous genes associated with coronary heart disease include LPA, 9p21.3 (a non -leading region affecting the expression of neighboring genes, such as CDKN2a And CDKN2B), Apoa5, APOE And CETP. These genes play a role in various processes, including lipoprotein metabolism, inflammation and vascular function.
• Hypertension: GWAS also revealed numerous genetic loci associated with hypertension. Some of the most famous genes associated with hypertension include AGT, ADD1, Nppo And Nos3. These genes play a role in the regulation of blood pressure through various mechanisms, including regulation of fluid volume, vasoconstriction and vasodilation.
• Stroke: Genetic risk factors of stroke are less studied than the genetic risk factors of coronary heart disease and hypertension. However, GWAS revealed some genetic loci related to a stroke, including 9p21.3, 12q24 And 1q22. These genes play a role in various processes, including blood vessels, inflammation and blood coagulation.

It is important to note that the presence of a genetic predisposition to the CVD does not mean that a person will necessarily develop the disease. Environmental factors, such as diet, lifestyle and the effect of toxins, also play an important role in the development of SVD. However, an understanding of the genetic basis of the SSZ can help identify people who are at a higher risk, and develop prevention and treatment strategies aimed at specific genetic goals.

5. Genetic testing of SSZ

Genetic testing is becoming increasingly affordable and is used to diagnose and assess the risk of SSZ. Genetic testing can be useful in the following situations:

• Diagnosis of monogenic SSZs: Genetic testing can confirm the diagnosis of monogenic CVD, such as family hypercholesterolemia, hypertrophic cardiomyopathy and marfan syndrome. Accurate diagnosis is important for the proper conduct and treatment of these diseases.
• SSZ risk assessment: Genetic testing can help evaluate the risk of developing SVD in people with a family history of the disease or other risk factors. Testing at risk polygenic indicators (PRS) uses information from GWAS to calculate the individual risk of developing CVD based on the human genetic profile.
• Direction of treatment: Genetic testing can help direct the treatment for treatment. For example, people with certain genetic options can react better to certain drugs or they may require more aggressive treatment.
• Family screening and counseling: Genetic testing can be used to scresh family members with mono -agenic SSZs to identify those who are at risk of developing the disease. Genetic counseling can provide information about the risk of inheritance of the disease and control options named after

It is important to note that genetic testing should be carried out in the context of genetic counseling. A genetic consultant can explain the advantages and limitations of genetic testing, interpret the results and provide recommendations for further maintenance and treatment.

6. Targeted therapy of SSZ based on genetics

Understanding the genetic basis of the SVAM paves the way to develop new targeted therapy strategies. Some examples:

• PCSK9 inhibitors: PCSK9 is a protein that regulates the level of LDL cholesterol in the blood. PCSK9 inhibitors are drugs that block the effect of PCSK9, which leads to a decrease in LDL cholesterol. These drugs are especially effective in people with family hypercholesterolemia caused by mutations in the gene PCSK9.
• Micrord -based therapy: Microrm is small RNA molecules that regulate the expression of genes. Microrm, as shown, play a role in the development of the CVD. Targeted therapy, aimed at certain microrm, may be a promising approach to the treatment of SVD.
• CRISPR-CAS9 General editing: CRISPR-CAS9 is a powerful technology for editing genes that can be used to correct the mutations that cause SVD. This technology is located in the early stages of development, but has a great potential for the treatment of genetic SSZs.
• Personalized medicine: Genomic information can be used to personalize the treatment of SVD. For example, people with certain genetic options can react better to certain drugs or they may require more aggressive treatment. Genomic information can also be used to predict the risk of SVD and develop individual prevention strategies.
• Proteom and metaboline markers: The identification of specific proteins and metabolites associated with certain genetic options can help in the development of more accurate and individual therapeutic approaches. This will aim at specific biological paths that are violated due to genetic factors.

7. Ethical and social issues related to the genetic research

Genetic studies of the SVD raise a number of ethical and social issues:

• Confidentiality: Genetic information is personal and confidential. It is important to protect the genetic information of people from unauthorized access and use.
• Discrimination: Genetic information can be used to discriminate people when hiring, insurance or other areas of life. It is important to adopt laws that protect people from genetic discrimination.
• Informed consent: People should give informed consent before participating in genetic studies or undergoing genetic testing. Informed consent should include information about the advantages and risks of research or testing, as well as how their genetic information will be used.
• Accessibility: Genetic testing and targeted therapy should be available to everyone who needs them, regardless of their socio-economic status or place of residence.
• Justice: It is important to ensure that genetic studies are carried out fairly and impartially, without discrimination on the basis of race, ethnicity or other secure characteristics.
• Interpretation of the results: The interpretation of genetic results can be complex and should be performed by qualified specialists. It is important to provide people with accurate and understandable information about their genetic results and their significance.
• Psychological impact: The results of genetic testing can have a significant psychological impact on people. It is important to provide people with psychological support and counseling in order to help them cope with the results of their genetic testing.

8. Future directions in genetic research of the SVD

The field of genetic studies of the SVD is developing rapidly. In the future, several key areas should be expected:

• Increase size GWAS and meta-analysis: The increase in the size of GWAS and the conduct of meta-analyzes from several GWAS will identify more genetic loci associated with the CVD, and increase the accuracy of an assessment of genetic risk.
• Using sequencing of the entire genome: Sequencing of the entire genome is becoming more and more affordable and can be used to identify rare genetic options that can cause SVD.
• Omix-data integration: The integration of Omix-data (genomics, transcription, proteomics, metabolomics) will make it possible to get a more complete idea of the molecular mechanisms underlying the SSZ, and identify new therapeutic goals.
• Development of personalized prevention and treatment strategies: Understanding the genetic basis of the SVA will develop personalized prevention and treatment strategies aimed at specific genetic goals and taking into account the individual characteristics of a person.
• Using artificial intelligence and machine learning: Artificial intelligence and machine learning can be used to analyze large arrays of genetic and clinical data, identifying patterns and predicting the risk of SVD.
• Pharmacogenomy: Studying the influence of genetic factors on the response to drugs. This will optimize drug therapy for each patient, based on his genetic profile.
• The study of the role of non -dodging DNA: Most of the human genome does not encode proteins, but can play a regulatory role in genes expression. Further studies of non -dodging DNA can identify new genetic risk factors of the CVD.
• The study of the role of microbioma: The intestinal microbia can affect the development of the CVD. The study of the interaction between human genetics and microbioma can lead to the development of new strategies for the prevention and treatment of SVD.
• Development of new genetic testing technologies: The development of faster, cheap and accurate technologies of genetic testing will expand the use of genetic testing in clinical practice.

In conclusion, genetics plays an important role in the development of SVD. Understanding the genetic foundation of the SVD is crucial for the development of new strategies for prevention, diagnosis and treatment. Achievements in the field of genetic research promise to improve the health of the heart and blood vessels in the future.

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