Gene-Environment Interactions in Asthma: Genetic and Epigenetic Effects

Abstract

Over the past three decades, a large number of genetic studies have been aimed at finding genetic variants associated with the risk of asthma, applying various genetic and genomic approaches including linkage analysis, candidate gene polymorphism studies, and genome-wide association studies (GWAS). However, contrary to general expectation, even single nucleotide polymorphisms (SNPs) discovered by GWAS failed to fully explain the heritability of asthma. Thus, application of rare allele polymorphisms in well defined phenotypes and clarification of environmental factors have been suggested to overcome the problem of 'missing' heritability. Such factors include allergens, cigarette smoke, air pollutants, and infectious agents during pre- and post-natal periods. The first and simplest interaction between a gene and the environment is a candidate interaction of both a well known gene and environmental factor in a direct physical or chemical interaction such as between CD14 and endotoxin or between HLA and allergens. Several GWAS have found environmental interactions with occupational asthma, aspirin exacerbated respiratory disease, tobacco smoke-related airway dysfunction, and farm-related atopic diseases. As one of the mechanisms behind gene-environment interaction is epigenetics, a few studies on DNA CpG methylation have been reported on subphenotypes of asthma, pitching the exciting idea that it may be possible to intervene at the junction between the genome and the environment. Epigenetic studies are starting to include data from clinical samples, which will make them another powerful tool for research on gene-environment interactions in asthma.

Large-scale Genetic Analysis Identifies 66 Novel Loci for Asthma

“…GxE interactions are also recognized as important components of asthma's complex genetic etiology but progress in this area been limited, with most studies focusing on exposures such as allergens, cigarette smoke, and air pollutants 43,44 . Our data suggest that sex is another potentially important endogenous environmental factor that can modulate risk through interactions with asthma susceptibility alleles, both individually or as a function of cumulative genetic burden.…”

B7-H3 participates in the development of Asthma by augmentation of the inflammatory response independent of TLR2 pathway

“…Asthma is a chronic airway inflammatory disease with complex pathogenesis, which is closely related to hereditary factor, environmental factor and organism immunity factor141516. Classical immune theories show that the imbalance of Th1/Th2 cells in organism plays an important role in the development of asthma1718.…”

Однонуклеотидний поліморфізм rs510432 гена автофагії 5 та розвиток «атопічного маршу» у дітей

“…Спільні генетичні варі-анти, таким чином, мають плейотропний ефект і є об'єктом активного вивчення, оскільки саме вони визначають перспективні напрямки терапії АЗ [9]. На сьогодні відомо більше ніж 300 генів, однону-клеотидні поліморфізми в яких асоційовані із роз-витком атопічних захворювань [14,22]. Для сис-тематизації отриманих даних використовуються різні класифікації кандидатних генів.…”