Heredity and allergies: the role of genes in the development of allergic reactions

Heredity and allergies: the role of genes in the development of allergic reactions

I. Introduction: The complexity of the interaction of genes and the environment in the development of allergies

An allergy, defined as an abnormal and exaggerated immune reaction to usually harmless substances (allergens), is a growing problem of public healthcare around the world. The growing prevalence of allergic diseases, such as allergic rhinitis, asthma, atopic dermatitis and food allergies, emphasizes the need for a deep understanding of the main mechanisms underlying their development. Although the role of environmental factors, such as the impact of pollutants, a change in the lifestyle and change in the diet, is indisputable, genetic predisposition plays a decisive role in determining the receptivity of the individual to the development of allergic reactions. This fact emphasizes the complex interaction of genes and the environment in the pathogenesis of allergies.

II. Genetic predisposition to allergies: atopia as a key factor

The key concept in understanding the genetic role in allergies is the “atopie”. Atopia is defined as a genetic predisposition to the production of immunoglobulin E (IGE) in response to general environmental allergens. People with atopia have an increased probability of developing allergic diseases. Family studies clearly demonstrated that in children whose parents suffer from allergies, the risk of developing allergies is significantly increased, which confirms a strong genetic component. The risk is even higher if both parents suffer from allergies. However, it is important to note that the genetic predisposition is not a guarantee of the development of allergies; Rather, it creates a background on which environmental factors can initiate and exacerbate allergic reactions.

III. Allergies related to allergies: candidate genes and research GWAS

The identification of specific genes involved in the development of allergies has become the subject of intensive research in recent decades. Two main approaches were used: research of candidate genes and common -grade associative studies (GWAS).

• Research of candidate genes: This approach is focused on evaluating options for certain genes, which, as you know, participate in immune reactions, barrier function or regulation of inflammation. Studies of candidate genes revealed a number of genes related to allergies, including:

  • Genes encoding cytokines and cytokine receptors: The cytokines play a decisive role in the regulation of the immune response, and the genetic options in genes encoding cytokines, such as IL-4, IL-5, IL-13 and IFN -γ, were associated with an increased risk of allergic diseases. For example, polymorphisms in the IL-4 gene, the key cytokine involved in the switching of IgE classes, are associated with increased IgE levels and increased susceptibility to atopy. Similarly, the IL-13 gene variants, which is involved in inflammation of the respiratory tract and the production of mucus, are associated with asthma and allergic rhinitis. Studies also showed the relationship between the polymorphisms of the cytokine receptor genes, such as IL-4Rα, and allergic diseases.

  • Genes participating in the presentation of the antigen: Genes of the main complex of histocompatibility (MHC), especially HLA genes (human leukocytal antigen), play a decisive role in the presentation of the antigen of T-cells. Certain HLA alleles were associated with an increased risk of developing specific allergic diseases. For example, Alleli HLA-DRB104 and HLA-DRB107 were associated with an increased risk of birch allergies. Genes involved in the treatment of antigens, such as TAP (a conveyor associated with antigens processing), were also investigated in their role in allergies.

  • Barrier function genes: Epithelial barriers, such as the skin and mucous membrane of the respiratory tract, play a decisive role in preventing the penetration of allergens. Genes involved in maintaining the barrier function, such as the Filaggrin gene (FLG), were recognized as important risk factors of atopic dermatitis. Mutations with a loss of function in the FLG gene lead to a violation of the barrier function of the skin, which allows allergens to penetrate and cause an immune response. Other genes involved in the barrier function, such as claudin and occlusin genes, are also studied in the context of allergies.

  • Genes of regulation of an immune response: Genes participating in the regulation of the immune response, such as CTLA-4 and PD-1, play a decisive role in maintaining immune tolerance and preventing autoimmunite. The options in these genes were associated with an increased risk of allergic diseases, probably due to a violation of the regulation of the immune response and increased sensitivity to allergens. FoxP3 transcription factor, which plays a key role in the development and function of regulatory T cells (TREGS), was also a subject of research in relation to its role in allergies.

  • Congenital immunity genes: Congenital immunity plays an important role in the initial recognition of allergens and the launch of an adaptive immune response. Genes encoding pattern recognition receptors (PRRS), such as TOLL-like receptors (TLRS), which recognize conservative molecular patterns associated with pathogens, and allergens, were associated with allergies. For example, the options in the TLR2 and TLR4 genes were associated with an increased risk of asthma and allergic rhinitis.

• General associative studies (GWAS): GWAS is a powerful approach that allows you to explore the entire genome for the presence of genetic variants (one -unique polymorphisms or SNP) associated with a certain sign or disease. GWAS has successfully identified numerous new loci associated with allergic diseases. These studies often reveal options in the non -dodging areas of the genome that can affect genes and expression.

  • Asthma: GWAS revealed numerous genetic locals associated with asthma, including genes involved in the functions of the respiratory tract, regulation of the immune response and inflammation. Some of the most reproducible locals associated with asthma include 17Q12-Q21 (contains ORMDL3 and GSDMB genes), IL33 and IL1RL1. The ORMDL3 gene is involved in the regulation of the metabolism of sphingolipids, which plays a role in the function of the respiratory tract. IL33 is a cytokine belonging to the IL-1 family, which is released by damaged epithelial cells and can activate immune cells. IL1RL1 encodes the IL-33 receptor.

  • Atopic dermatitis: Gwas significantly advanced our understanding of the genetic basis of atopic dermatitis. The strongest genetic association with atopic dermatitis is found in the FLG gene. GWAS also revealed other loci associated with atopic dermatitis, including genes involved in the regulation of the immune response, barrier function and inflammation.

  • Allergic rhinitis: GWAS revealed several genetic locals associated with allergic rhinitis, including genes involved in the regulation of the immune response, respiratory tract and inflammation.

  • Food allergies: GWAS began to detect genetic loci associated with food allergies, although food allergies genetics have been less studied than the genetics of other allergic diseases. Studies revealed genes involved in the regulation of the immune response and barrier function associated with food allergies.

IV. Genetic heterogeneity and endotypes of allergies

It is important to note that allergic diseases are genetically heterogeneous, which means that various genetic options can contribute to the development of allergies in different people. Moreover, allergic diseases are often divided into endotypes, which are subgroups of patients with distinct clinical, pathophysiological and genetic characteristics. Identification of allergies can help develop more purposeful and effective treatment methods. For example, asthma can be divided into endotypes based on factors that initiate the disease (for example, allergic asthma, non -allergic asthma, asthma caused by physical activity), the severity of respiratory tract inflammation (for example, eosinophilic asthma, neutrophilic asthma) and response to treatment. Understanding the genetic basis of these endotypes can help choose treatment for specific patients.

V. Epigenetics and allergies: modifications of genes without changing the sequence of DNA

Epigenetics refers to changes in genes expression, which are not associated with changes in the DNA sequence. Epigenetic mechanisms, such as DNA methylation, modification of histones and micrord (Mirnka), can play a role in the development of allergies. Environmental factors, such as the effects of allergens, pollutants and tobacco smoke, can cause epigenetic changes that affect the expression of genes associated with the immune response and inflammation.

• DNA methylation: DNA methylation is a process in which a methyl group joins the basis of cytosin in DNA. DNA methylation is usually associated with suppression of genes expression. Studies have shown that changes in DNA methylation patterlation can be associated with allergic diseases. For example, changes in the methylation of DNA of genes involved in the regulation of an immune response, such as IFN-γ and FoxP3, were found in people with allergies.

• Modification of histones: Histon is a protein around which DNA is accrue. Histonian modifications, such as acetylation and methylation, can affect the structure of chromatin and the availability of DNA for transcription. Changes in the modifications of histones were associated with allergic diseases.

• Microrm (Markn): Mirnka is small non-dodging RNA molecules that regulate the expression of genes, associated with MRNC targets. Mirnka play a role in various biological processes, including the regulation of an immune response and inflammation. Changes in the expression of Mirk were associated with allergic diseases. For example, Mirnka, which regulate the expression of genes involved in the switching of IgE classes, activation of mast cells and inflammation of the respiratory tract, were disregular in people with allergies.

VI. The interaction of genes and the environment: how the environment affects the genetic predisposition

As mentioned earlier, the development of allergies is the result of a complex interaction between a genetic predisposition and environmental factors. Genes create the basis, but environmental factors can initiate and aggravate allergic reactions.

• The effect of allergens: The effect of allergens, such as pollen, mites of domestic dust, pets hair and food, is an important environmental factor that can cause allergic reactions in genetically predisposed people. The time and dose of the effects of allergens can affect the development of allergies. The early exposure of certain allergens can lead to tolerance, while later or high exposure can cause sensitization.

• The impact of pollutants: The effect of air pollutants, such as diesel particles, ozone and solid particles, can enhance allergic reactions. Pollutants can damage the epithelial barrier, increase inflammation and enhance sensitization to allergens.

• Changes in the lifestyle: Changes in the lifestyle, such as a decrease in the effects of microbes in early childhood (hygienic hypothesis), changes in the diet and an increase in the use of antibiotics, were associated with an increase in the prevalence of allergic diseases. Hygienic hypothesis suggests that a decrease in the effects of microbes in early childhood can disrupt the development of the immune system and increase the risk of allergies.

• The effect of tobacco smoke: The effect of tobacco smoke, especially in early childhood, is a known risk factor for the development of allergic diseases such as asthma. Tobacco smoke can damage the respiratory tract, enhance inflammation and increase the susceptibility to allergens.

VII. The clinical value of the genetic studies of allergies: diagnosis, prevention and treatment

Genetic studies of allergies have a significant clinical potential for improving the diagnosis, prevention and treatment of allergic diseases.

• Diagnosis: Genetic testing can be used to identify people with an increased risk of allergies. This can be especially useful for children with a family history of allergies. However, it is important to note that the genetic testing of allergies is still in the early stages, and only a small number of genetic tests that have clinical value are available.

• Prevention: The identification of people with a genetic predisposition to allergies can allow to take preventive measures to reduce the risk of developing allergic diseases. These measures may include avoiding the effects of allergens, breastfeeding and the effects of microbes in early childhood.

• Treatment: Genetic studies can help develop more purposeful and effective methods of treating allergic diseases. For example, an understanding of the genetic basis of allergy endotypes can help choose treatment for specific patients. Medicines are developed that are aimed at specific genetic paths involved in allergies.

VIII. Ethical and social consequences of the genetic testing of allergies

The genetic testing of allergies raises ethical and social issues that must be carefully taken into account.

• Confidentiality: Genetic information is personal and confidential, and it is important to protect it from unauthorized access.

• Discrimination: There is a risk that genetic information will be used to discriminate people with a genetic predisposition to allergies in relation to insurance, employment or education.

• Genetic counseling: It is important to provide genetic counseling to people undergoing genetic allergies so that they can understand the risks and advantages of testing.

• Commercialization: It is important to ensure that the genetic testing of allergies is offered to be responsible and that the commercialization of testing does not ahead of science.

IX. Future directions: full -genome sequencing, multi -municipality and personalized medicine

The future of allergies of allergies is the use of advanced technologies, such as full -genomic sequencing, multi -municipality and personalized medicine.

• Full -seed sequencing: Full -seed sequencing allows you to sequenate the entire human genome, providing the most complete information about the genetic predisposition of a person to allergies.

• Multimica: Multimica is an approach that combines data from various ohmic technologies, such as genomic, transcriptomics, proteomics and metabolomics, to ensure a holistic idea of biological processes involved in allergies.

• Personalized medicine: Personalized medicine is an approach to medicine, which adapts treatment to the individual characteristics of the patient, including his genetic profile. Personalized medicine can be used to develop more purposeful and effective methods of treating allergic diseases.

X. Models on animals in the study of allergies genetics

Models on animals play an important role in the study of allergies genetics. These models allow researchers to explore complex interactions between genes and the environment that contribute to the development of allergic diseases. Some of the usually used animal models to study allergies include mice, rats and guinea pigs.

• Mouse models: Mice are the most commonly used animal models for studying allergies. They are easily genetically modified, which allows researchers to study the role of specific genes in the development of allergic diseases. Mouse models of asthma, atopic dermatitis and food allergies were developed to study the mechanisms underlying these diseases.

• Rat models: Rats are also used to study allergies, although less common than mice. Rats have great physiology than mice, which can make them more suitable for studying certain aspects of allergies, such as inflammation of the respiratory tract.

• Models on guinea pigs: Guinea pigs were used to study allergies for many years. They are especially useful for the study of bronchonkhoncontation, characteristic of asthma.

XI. Tasks and limiting genetic allergies

Despite the significant progress achieved in the genetic studies of allergies, several tasks and restrictions remain.

• Genetic heterogeneity: Allergic diseases are genetically heterogeneous, which means that various genetic options can contribute to the development of allergies in different people. This complicates the identification of specific genes involved in allergies.

• The interaction of genes and the environment: The development of allergies is the result of a complex interaction between a genetic predisposition and environmental factors. It is difficult to unravel the relative contribution of genes and the environment to the development of allergies.

• Sample size: To identify genetic options associated with allergies, large sample sizes are required. This may be a problem, especially for researching rare allergic diseases.

• Ethnic differences: The prevalence of allergies and genetic variants associated with allergies can vary between ethnic groups. It is important to take into account ethnic differences in conducting genetic allergies.

• Functional abstract: Many genetic options associated with allergies are in the non -dodging areas of the genome, and it is difficult to determine their functional meaning. Additional studies are needed to clarify the functional role of these options.

XII. Practical tips for people with the family history of allergies

For people with the family history of allergies, you can consider several practical tips in order to reduce the risk of allergic diseases.

• Breast-feeding: Breastfeeding is recommended for at least six months, as it can help protect babies from the development of allergies.

• Introduction of solid food: Solid food should be administered gradually, starting from about six months. The introduction of Allergenic Foods, Such AS Peanuts and Eggs, Early in Life can help prevent the development of food allergies. (I don’t translate it specifically, because the question is debatable, and you should focus on the current recommendations of the pediatrician).

• Environmental control: Environmental control, in order to reduce the effects of allergens, such as mites of domestic dust, pets and pollen, can help prevent the development of allergic diseases.

• Avoiding tobacco smoke: Avoiding the effects of tobacco smoke, especially in early childhood, can help prevent the development of allergic diseases.

• Probiotics: Some studies have shown that probiotics can help prevent the development of allergic diseases in high -risk infants. However, additional studies are needed to confirm these results.

XIII. Glossary of key terms

• Allergies: An abnormal and exaggerated immune reaction to usually harmless substances (allergens).
• Allergen: A substance that causes an allergic reaction.
• Atopy: A genetic predisposition to the production of immunoglobulin E (Ige) in response to general environmental allergens.
• IgE: Immunoglobulin E is an antibody that plays a key role in allergic reactions.
• Cytokines: Proteins that play a role in regulating an immune response.
• HLA: Human leukocytic antigen is a gene that plays a role in the presentation of the antigen of T-cells.
• Filaggrin (FLG): Protein that plays a role in the barrier function of the skin.
• General associative studies (GWAS): A powerful approach that allows you to explore the entire genome for the presence of genetic options (one -okleotide polymorphisms or SNP) associated with a certain sign or disease.
• Eldotip: The subgroup of patients with distinct clinical, pathophysiological and genetic characteristics.
• Epigenetics: Changes in the expression of genes that are not associated with changes in the DNA sequence.
• DNA methylation: A process in which a methyl group joins the basis of cytosin in DNA.
• Microrm (Markn): Small non-dodging RNA molecules that regulate the expression of genes, associated with MRNC targets.

XIV. List of used literature (supposed, requiring filling out real sources)

• (List of scientific articles and reviews on the topic)

XV. Further research and resources

• (Links to websites and organizations providing information about allergies)