Genetics of asthma☆,☆☆,★
Section snippets
PHENOTYPE DEFINITION
Asthma is an increasingly common disease that is characterized by variable airway obstruction and bronchial hyperresponsiveness (BHR) and is caused by acute and chronic bronchial inflammation.3, 4 Clearly defining the disease phenotype is a central issue in genetic studies, where it may be necessary to evaluate family members who have not been previously evaluated or diagnosed. Current definitions of asthma describe its pathophysiologic basis, emphasizing the importance of inflammatory
GENETIC STUDIES OF ASTHMA
Evidence for a genetic component in complex diseases to eventual identification of disease genes generally progresses through several types of genetic studies (Fig 1). The following paragraphs will discuss evidence for a genetic component for asthma, chromosomal regions believed to harbor asthma susceptibility disease genes, association or candidate gene studies, and recent technology to identify multiple functional consequences of genetic variation (functional
ENVIRONMENTAL RISK FACTORS FOR ASTHMA
An environmental component in the pathogenesis of asthma is well accepted, as is the potential for gene-environment interaction. The following is a review of some of the important environmental risk factors believed to contribute the asthma phenotype.
GENE-ENVIRONMENT INTERACTIONS
Current concepts of asthma pathogenesis postulate that onset of the disease and its clinical course are determined by gene-environment interactions, that is, those persons in whom asthma develops are both genetically susceptible and receive an appropriate environmental stimulus. Across the range of asthmatics in the population, the relative influence of genes and environmental factors probably varies. Gene-environment interactions can be assessed in case-control and cohort studies as well as in
CONCLUSION
Susceptibility to development of asthma is the result of multiple environmental risk factors and multiple genes. Genetic studies of asthma continue to provide insight into the pathophysiologic mechanisms of the disease. This should ultimately lead to new and more effective therapeutic interventions, new diagnostic methods for presymptomatic diagnosis, the development of strategies for disease prevention in susceptible individuals, and delineation of the interaction between genotype and the
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Cited by (77)
Interleukin 4 and Interleukin 4 receptor alpha gene variants and risk of atopy - A case control study based assessment
2021, Clinical ImmunologyCitation Excerpt :In recent years, a high serum levels of IgE is used to predict the development of asthma, independent of other allergic factors. Therefore, an understanding of the genetic mechanisms regulating total serum IgE levels will validate the efforts to scrutinize the hereditary components of different atopic disorders, complex genetic disorders influenced by the interactions among multiple genes and environmental exposures [38]. In another study, a two-locus segregation analysis revealed evidence of two major genes and a residual genetic effect regulating total serum IgE levels in the first set of 92 Dutch families ascertained through a parent with asthma [39].
Ecological determinants of respiratory health: Examining associations between asthma emergency department visits, diesel particulate matter, and public parks and open space in Los Angeles, California
2019, Preventive Medicine ReportsCitation Excerpt :For example, research has emphasized the relationship between increased exposure to indoor allergens and asthma (Finkelstein et al., 2002; Gelber et al., 1993; Kanchongkittiphon et al., 2015; Pomés et al., 2016; Salo et al., 2008). However, evidence suggests that aside from potential susceptibility genes, exposure to proximal and distal environmental factors (e.g., indoor and outdoor air pollution) may be associated with asthma prevalence among a range of ethnocultural groups (Holgate, 1999; Torgerson et al., 2011; Wiesch et al., 1999). More specifically, indoor and outdoor air pollutants, as well as exposure to environmental tobacco smoke and pollen allergens, have been linked to disease inception and long-term severity and progression (Brunekreef, 2004; Holgate et al., 2007).
Molecular and genomic basis of bronchial asthma
2019, Clinical Molecular Medicine: Principles and PracticeA panel study of airborne particulate matter composition versus concentration: Potential for inflammatory response and impaired pulmonary function in children
2017, Allergology InternationalCitation Excerpt :Nasopharyngeal dysfunction caused by allergic rhinitis is one cause of bronchoconstriction.46 In children, atopy is associated with airway hyperresponsiveness, which can increase airway sensitivity.47 Therefore, the present study adjusted the analyses for allergic diseases.
Association between pulmonary function and daily levels of sand dust particles assessed by light detection and ranging in schoolchildren in western Japan: A panel study
2016, Allergology InternationalCitation Excerpt :Park and Yoo found a relationship between ADS occurrence and PEF in South Korean children with asthma, but other South Korean study was unable to find any relationship between ADS events and PEF in children without asthma.15,16,30 There is a relationship between atopic disposition and airway hyperresponsiveness in children.31 The influence of air pollutants on airway may differ depending on whether allergic diseases are present.
Genetics and Epigenetics of Allergic Diseases and Asthma
2014, Middleton's Allergy: Principles and Practice: Eighth Edition
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Supported by National Institutes of Health grants No. R01-HL48341 and U01 HL/AI49602.
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Reprint requests: Eugene R. Bleecker, MD, Center for the Genetics of Asthma and Complex Diseases, University of Maryland, Baltimore, 108 N Greene St, Suite 119, Baltimore, MD 21201.
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0091-6749/99 $8.00 + 0 1/1/102654