Year: 2006
Type: review
Abstract: Asthma is a complex disease with a diverse genetic and environmental component. 1Asthma shows a high level of phenotypic heterogeneity characterised by obstruction of the airways of the lung and is related with atopy, bronchial hyperresponsiveness (BHR), and increased IgE levels.3][4][5] It has been estimated that about 300 million persons worldwide have asthma (http://www.ginasthma.com/).Studies in twins and family studies indicate that the genetic component of asthma is likely to be high, [6][7][8][9] although the individual genes identified have only modest effects and an unknown pattern of inheritance.The most common chromosomal linkage regions observed in genome-wide linkage studies are 2q14-q32, 5q31-q33, 6p21.3,7q31, 11q13, 12q14.3-q24.31,13q14, 14q11.2-q13,16p21, 17q11.2, and 20p13. 1 4 Several asthma and atopy genes have been identified by positional cloning including the genes ADAM33, PHF11, GPRA, DPP10, and SPINK5, 4 10 and numerous other genes have been investigated as candidate genes based on their function.Many environmental factors have been associated with incidence or prevalence of asthma although there is still limited knowledge of major causes of asthma in the general population.Air pollutants (particles, diesel exhaust, PAHs) are inducers of oxidative stress that could play a role in allergic inflammation and in inducing acute asthma exacerbations. 11 12Several studies have associated asthma with different indoor air pollutants: dampness, newly painted dwelling, indoor higher levels of CO 2 , exposure to NO 2 (gas cookers), formaldehyde, and total concentration of VOCs and higher levels of terpenes. 13Passive smoking/environmental tobacco smoke (ETS) is a well studied exposure, that has been associated with respiratory symptoms, lower lung function, BHR, severity of asthma, and increasing levels of total IgE. 14Occupational exposures cause around 15% of adult asthma. 15Around 250 specific occupational exposures have been associated with asthma; occupations at high risk include farmers, painters, plastics workers, and cleaners. 16iming of exposure seems to be important.This is exemplified by the low asthma and atopy risk in children growing up in farms that are more exposed to infections and allergens. 17 18This low risk has been attributed to what has been described as the ''hygiene hypothesis'', postulating that lack of contact with infectious agents in early age could prevent the evolution of the Th2 immune profile of the newborn (pro-allergic) towards a Th1 profile (anti-infectious). 19 An individual's predisposition to disease may affect the response to environmental or occupational exposures.Increasing evidences in the last decade suggest that gene-environment interactions play a critical role in pathogenesis of complex diseases like asthma, with multiple genes (each one with modest effects) operating in conjunction with multiple environmental or occupational exposures.Studies of interactions of genes and the environment may help elucidate the mechanisms of disease, identifying specific genes, or exposures involved in the same pathway.This information could also help design strategies of intervention and preventive advice, and of therapeutic intervention on the population at risk. 20he meaning of ''interaction'' remains controversial in biomedical research.A more biological oriented definition refers to interaction as the co-participation of two factors (gene and environment) in the same causal mechanism of disease. 4From a statistical point of view, gene- environment interaction would imply a change in the effect of exposure to an environmental factor due to a genetic variant, or vice versa. 21 22A statistical interaction does not necessarily imply a biological interaction.Furthermore, when discussing statistical interactions it is important to define the measure of risk examined and the type of model used, for example multiplicative or additive models.Several categories of genes have been examined in studies on gene-environment interactions in asthma.Genes have been selected on the basis of previous evidence of involvement in asthma or related phenotypes, or previous evidence of interaction with the environmental cause under study irrespective of prior evidence of asthma.Examples of different categories of genes include: (i) genes that could be involved in the metabolism of substances producing asthma (e.g.N-acetyl transferases and isocyanates); (ii) genes induced in response to oxidative stress (e.g.GSTs, NQO1) which are related to exposures that induce asthma by production of reactive oxygen
Authors: F Castro-Giner, F Kauffmann, R de Cid, M Kogevinas
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2157692694