Genetic and environmental interaction in allergy and asthma☆☆☆

Abstract

Asthma is an inflammatory disorder of the airways involving coordinate up-regulation of T(H)2-type cytokines encoded in a cluster on chromosome 5q(31-33) on T cells and inflammatory cells. There is also a requirement for local airway susceptibility factors that, together with T(H)2 polarization, results in hyperresponsiveness, variable airflow obstruction, and, over time, remodeling of the airway wall. Asthma has strong genetic and environmental components that interact both in the induction and subsequent expression of the disease phenotypes. Multiple genes are involved and probably interact. Whole genome screens are beginning to identify gene-rich regions of special relevance to asthma and atopy, although a novel disease-related gene has yet to be discovered from these. By contrast, there are a plethora of candidate genes whose function in relation to disease pathophysiologic mechanisms and response to treatment are known. Two examples are polymorphisms involving IL-4 receptors and the enzymes controlling cysteinyl leukotriene production. Abnormal signaling between the epithelium, which is in contact with the environment, and the underlying (myo)fibroblasts and dendritic cells indicating reactivation of the epithelial mesenchymal trophic unit, which is involved in fetal lung development and branching, provide a basis for asthma that encapsulates both T(H)2 polarization and airway wall remodeling.

GlutathioneS-Transferases M1 and P1 Prevent Aggravation of Allergic Responses by Secondhand Smoke

“…We also observed that individual responses to SHS and DEPs are correlated across the endpoints measured in this study. Our results provide further evidence that the severity of common allergic airway diseases, such as allergic rhinitis and asthma, is a consequence of the interplay between common genetic variants and environmental exposures (9,(35)(36)(37). The correlated responses to different exposures suggest that some individuals are at higher risk than others for…”

Length at Birth and Effect of Prenatal and Postnatal Factors on early Wheezing Phenotypes. Kraków Epidemiologic Cohort Study

“…It is worthwhile underlining that the prenatal ETS exposure appeared to have a stronger and signifi cant effect on the occurrence of persistent wheezing than that in the postnatal period. The inverse association between the infant's length at birth and persistent wheezing could indicate that a shorter length of the newborns is a proxy measure of a slower biological maturation of the respiratory tract, which obviously depends on many factors, including among others the induction and maturation of the target lung cell population, as well as their relevant enzyme and detoxication systems [33][34][35][36][37]. Animal studies indicated that both intrauterine and postnatal exposure to air pollutants can lead to impaired lung growth [38].…”

Epigenetic inheritance of fetal genes in allergic asthma

“…It has been suggested that a reactivation of the epithelialmesenchymal trophic unit may exist in asthma (51). We would like to extend this notion by proposing that this trophic unit still exists at birth in the neonate who will develop asthma, suggesting the persistence of immature features of the developing lung.…”

“…In asthma, abnormal signaling between the epithelium, in contact with the environment, and the underlying (myo)fibroblasts and dendritic cells may reactivate the epithelial-mesenchymal trophic unit, which is involved in fetal lung development and branching (42,51). There are several features of the developing lung which are present in asthma, and it has been observed that allergen exposure induces the expression of some of the these Katz (39) proposed the concept of the Ôallergic breakthroughÕ.…”