Does asthma run in the family? Medically reviewed by Adithya Cattamanchi, M. Is asthma genetic? Causes Risk factors Symptoms Treatment Summary Asthma can be genetic, though not all cases of asthma are inherited.
Are different types of asthma genetic? What triggers asthma? Risk factors. Asthma Genetics Pulmonary System Respiratory. Exposure to air pollutants may amplify risk for depression in healthy individuals. Costs associated with obesity may account for 3.
Related Coverage. What to do at home for an asthma attack Asthma attacks can be frightening, especially if a person is unprepared. What are the treatments for asthma?
Medically reviewed by Debra Sullivan, Ph. What is a bronchospasm and what causes it? Medically reviewed by Alana Biggers, M. Who gets asthma? Why do people get asthma? Family History and Genetics Children of mothers with asthma are three times more likely to suffer from asthma, and 2. Allergies People are more likely to have asthma if they have certain types of allergies, such ones which can affect the eyes and nose. Premature Birth Children born before 37 weeks are at increased risk of developing asthma later in life.
Lung Infections Babies or small children may be at risk of developing asthma later in life if they had certain lung infections at a very early age. Occupational Exposures There are more than substances including gases, dust participles and chemical fumes and vapours that can cause asthma in the workplace. Hormones Women can develop adult-onset asthma during or after menopause. Environment Air Quality Smoking, exhaust fumes and airborne particulate matter can be linked to causing asthma.
Obesity Extra weight around the chest might squeeze the lungs and make it more difficult to inhale. Asthma Control. Learn More. Asthma Diagnosis. Asthma FAQs. Asthma Triggers. Severe Asthma. There are also practical lifestyle steps that you can take, in conjunction with using your inhalers and taking medication as guided by your doctor.
Does Asthma Run in the Family? Is asthma genetic? Is there an asthma gene? Asthma genetic factors Several genetic factors can predispose you to a greater risk of developing asthma. These include: Your family history Your gender.
Asthma and family history Numerous studies have found that your family history can be a risk factor for the development of asthma. Asthma and gender Studies have found that asthma is more common in young boys, whereas girls are more likely to be affected after puberty. Is hereditary asthma curable? These include: Exercising regularly — once your asthma is under control, regular exercise is beneficial Eating healthily — a balanced diet with plenty of fresh fruit and vegetables is advised; being overweight can exacerbate asthma Not smoking — smoking is a known irritant and stopping smoking can reduce the frequency and severity of your symptoms.
In this study the monozygotic MZ concordance for self-reported asthma was 19 per cent and dizygotic DZ concordance was 4. Another large Finnish study investigated 13, twin pairs and showed a concordance rate of 0. Duffy et al 32 in a questionnaire-based study of 3, Australian twin pairs showed a correlation of self-reported asthma of 0.
The heritability was 60 per cent for females and 75 per cent for males. Harris et al 33 studied 5, Norwegian twins in a study on health and development in Oslo.
The proband-wise concordance for asthma was 0. The heritability of asthma was approximately 79 per cent, whereas 21 per cent was due to unique environmental factors Huovinen et al 35 have studied Finnish twin pairs, and reported that in addition to allergic diseases, educational level and physical activity were associated with adult onset asthma.
Nystad et al 36 have studied pairs of Norwegian twins aged yr and established that the phenotypic correlation between disease and symptom was 0. Twin studies have generally shown that concordance rates for asthma are significantly higher in MZ twins than in DZ twins, whether reared apart or together. Broad-sense heritability estimates derived from twin studies range from 36 to 75 per cent Twin studies have revealed a 0. Segregation analysis can provide insight into the genetics of a trait, e.
Using this type of analysis, the heritability, mode of inheritance, penetrance and frequency of a trait are being estimated and also indicated the involvement of major genes 6. A large study performed by the European Community Respiratory Health Survey Group analyzed the pooled data from 13, families consisting of 75, randomly selected individuals using complex seg-regation analysis.
The results of this study showed further evidence of genetic regulation of asthma and a model with a two-allele gene with codominant inheritance fitted the data best, assuming a major gene has to be involved in the pathogenesis of asthma, but the penetrance of such a gene is low Jenkins et al 38 presented a segregation analysis of 7, families in which A segregation analysis of physician-diagnosed asthma in 3, randomly selected individuals from nuclear families done by Holberg et al 39 in Tucson, AR, USA, showed evidence of a polygenic or an oligogenic model with some evidence of a recessive gene, explaining only part of the segregation.
Many segregation analyses of total serum IgE-concen-tration in asthma have been studied and most of these studies conclude that IgE levels are highly heritable. Several studies have shown a strong association between atopy and bronchial hyper-responsiveness 40 — The complexity of the immunological network involved in the pathogenesis of asthma, atopy, its related traits and the existence of different asthma phenotypes are consistent that different genes may be involved in the pathogenesis of asthma 6.
Ober et al 43 conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry, to identify genes that influence asthma and asthma-associated phenotypes.
A primary sample of individuals and a replication sample of individuals were evaluated by a genome-wide screen using autosomal and three X-Y pseudoautosomal markers. They showed markers in four regions 5q, 12q Recently, Pillai et al 44 have identified five major quantitative asthma phenotypes. Kleeberger and Peden 45 have studied different environmental factors physical, chemical, nutritional, behavioral, etc.
Bouzigon et al 47 reported that polymorphisms in 17q21 confer higher risk in early onset asthma and the risk increases further when there is exposure to environmental tobacco smoke in early life. This region contains four genes all of which could have potential role in asthma pathogenesis 46 , Teerlink et al 48 revealed genome-wide significant evidence of linkage to region 5q13 and suggestive evidence for linkage to region 6p Both the 5q13 and 6p21 regions were previously identified as regions of interest in other genome-wide scans for asthma-related phenotypes Table II provides the chromosome regions involved in causing asthma identified by linkage analysis.
More than loci on 22 autosomes, X and Y chromosomes have been linked to asthma 8 , 10 , 49 , Chromosome 12 appears to harbour maximum susceptible genes for asthma than any other chromosome. Interestingly, only one locus has been established on each of chromosomes 3, 15, 18 and Of these loci associated with asthma, some had very strong association. Table II shows the list of common candidate genes in asthma with their locations derived from a large number of single nucleotide polymorphisms SNPs studies.
The following are some of the extensively studied candidate genes and SNPs associated with asthma, with special reference to studies in the Indian population:. This gene has been identified by positional cloning and localized on to chromosome 20p13 as a susceptibility gene for asthma This is the most extensively studied and highly polymorphic gene with bps, 22 exons and 21 introns.
Case-control and family-based association studies have confirmed a link between ADAM33 and asthma. Its restricted expression to mesenchymal cells as well as its association with bronchial hyper-responsiveness and accelerated decline in lung functions over time strongly point to its involvement in the structural airway components of asthma.
Extensive alternative splicing, expression during branching morphogenesis in the developing foetus, impaired lung function in childhood, the production of a soluble form linked to chronic asthma, and tight epigenetic regulation indicate a level of complexity in the way ADAM33 influences the disease phenotype.
ADAM33 function includes activation, proteolysis, adhesion, fusion, and intracellular signaling. The crystal structure of the catalytic domain of ADAM33 has been resolved around the nonselective matrix metalloproteinase inhibitor marimastat in addition to the zinc binding site Angela et al 80 supported the hypothesis that ADAM33 polymorphisms influence lung function in early life and epithelial-mesenchymal dysfunction in the airways may predispose individuals toward asthma, being present in early childhood before asthma becomes clinically expressed.
Polymorphisms in the ADAM33 are associated with an accelerated decline in forced expiratory volume in the first second FEV1 in the spirometery of general population and these are not only risk factors for the development of asthma, but also for COPD. Thus, polymorphisms in ADAM33 constitute important risk factors for the development of respiratory diseases in a large subset of the general population Interleukin-4 IL-4 : This is located on chromosome 5 at position q31 with bps, 10 exons and 9 introns.
IL-4 is a cytokine secreted by helper T cell type 2 TH-2 cells that stimulates the production of IgE and induces eosinophil-mediated attacks against allergens Chiang et al 83 established that polymorphism in the promoter of the IL-4 is associated with asthma and is a disease modifier in terms of the severity of airway hyper-responsiveness AHR.
Nagarkati et al 85 indicated that the promoter of the IL4 gene is invariant in Indian population and Bijanzadeh et al 81 reported that there are no significant association between this SNP of the IL-4 and asthma in an Indian population. This is responsible for immediate reactions and also is found on the surface of mast cells, basophils, eosinophils and Langerhan's cells. The binding of allergen to the receptor-bound IgE leads to degranulation of the cell and the synthesis and release of cytokines IL-4 , and activated inflammatory cells.
PDH finger protein 11 PHF11 : This is localized on chromosome 13q14 and contains 10 exons, 9 introns and with bps. Public databases identified an alternative first exon with multiple overlapping variants that produce alternative start methionines for protein translation This gene is located on chromosome 16 and represents an ideal candidate gene for atopy susceptibility because of its pivotal role in IL-4 signaling and its key role in allergic inflammation by promoting IgE production and Th2 cell development 72 , A hierarchical genotyping design was used to identify this gene.
The data implied that this gene is involved in the pathogenesis of atopy and asthma and may have application in other inflammatory diseases Dipeptidyl-peptidase 10 DPP10 : This is localized on chromosome 2qq32 and shares features with members of the S9B family of DPP serine proteases, which includes DPP4, a widely expressed enzyme that plays a central role in chemokine processing as part of the innate immune system.
The locus displays a complex pattern of transcript splicing, with eight alternate first exons; four of which strongly associated with asthma Interferon gamma IFNG : This locus is localized on 12q21 and established as a candidate gene for asthma on the basis of its role in pathophysiology and positive linkage demonstrated in some populations INPP4A is a magnesium independent phosphatase which negatively regulates PI3K-Akt signaling important for various pathophysiological pathways in asthma CD 14 : The gene for CD 14 receptor is located on chromosome 5q An association between CT functional polymorphism and asthma has been demonstrated 49 , 50 , An association with polymorphisms has been associated with asthma in both atopic and non-atopic subjects and with elevated total serum IgE levels 49 , 50 , 92 , Clara cell secretory protein CC16 : The genes for Clara cell secretory protein is localized on the chromosome 11q13 and encodes a 16kDa protein secreted from the Clara cells in the respiratory system.
It is an important anti-inflammatory molecule limiting the synthesis of leucotrienes and prostaglandins and inhibits chemotaxis of inflammatory cells. An association with asthma has been demonstrated in both family-based and case-control studies 50 , Uteroglobin related protein1 UGRP1 : The genes for uteroglobin related protein 1 is localized on the chromosome 5q32 and encodes for a secretory protein in the airways with anti-inflammatory activity.
Studies evaluating polymorphisms in URGP1 have demonstrated both association 61 and lack of association with asthma It is a member of the STAT family of transcription factors which plays a central role in IL-4 mediated biological responses. An association with asthma has been demonstrated in the Indian population 49 , Mast cell chymase CMA1 : The gene for mast cell chymase is located on chromosome 14q An association has been observed with asthma and increased total IgE N-acetyltransferase 2 NAT2 : The gene for NAT2 is located on chromosome 8p22 and is responsible for N-acetylation and influence susceptibility to atopic disorders.
An association with asthma, increased total IgE and eosinophilia has been observed in the Indian population 49 , 97 , Late cornified envelope like proline-rich1 LELP1 : The gene for LELP1 is located in chromosome 1q21 and encompasses a small proline rich protein gene cluster and has been associated with atopy IL is an anti-inflammatory cytokine primarily produced by monocytes and macrophages and plays a key role in asthma It is important in asthma as it also regulates IgE production and has been implicated in asthma These are the most common genes studied worldwide.
The association of asthma with the remaining genes is less established and their study is restricted to a limited population.
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