Gene–environment interactions in asthma

Asthma is a complex disease with a diverse genetic and environmental component.¹ Asthma 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. Over the last decades asthma has become a major cause of morbidity in children from developed countries with an estimated prevalence of 5–10%.^2–5 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,^6–9 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.^11,12 Several studies have associated asthma with different indoor air pollutants: dampness, newly painted dwelling, indoor higher levels of CO₂, exposure to NO₂ (gas cookers), formaldehyde, and total concentration of VOCs and higher levels of terpenes.¹³ Passive smoking/environmental tobacco smoke (ETS) is a well studied exposure, that has been associated with respiratory symptoms, lower lung function, BHR, severity of asthma, …