Genetics of Complex Airway Disease

Abstract

The past 3 years have seen highly significant genetic effects identified for a wide variety of common complex diseases, including the airway disorders of asthma and chronic obstructive pulmonary disease. It appears that only a portion of the genetically mediated susceptibility to complex diseases has been identified, and there is much left to be discovered. This review briefly describes the results of the genome-wide association studies of asthma and gives an overview of the parallel and increasingly large-scale studies that are taking place with chronic obstructive pulmonary disease. The future impact is discussed of technological advances that allow increasingly large-scale gene expression studies, next-generation sequencing, and genome-wide testing for epigenetic effects. The use of genetic technology to examine the airway microbiota that interact with the mucosa in health and disease is described.

The Clinical and Environmental Determinants of Airway Transcriptional Profiles in Allergic Asthma

“…Although host factors that make one susceptible to asthma are complex and poorly understood, it is clear that a genetic component to asthma susceptibility exists (1)(2)(3). Although genes and genetic loci that have been implicated in asthma are numerous, validation in independent cohorts and populations has been largely unsuccessful (1).…”

Genetic and genomic approaches to asthma

“…An exception to this may be the IL4/IL13 locus on chromosome 5, which showed significant association to the total serum IgE concentration as well as to doctor-diagnosed asthma [10 && ]. This finding suggests that elevation of IgE is likely to be an inconstant secondary effect of asthma rather than its cause [52], but it does not exclude a significant role for atopic mechanisms in modifying the severity of the inflammation in asthmatic airways.…”

“…This might be because of multiple small effects, rare highly penetrant mutations or epigenetic effects [52]. It is also influenced by the variation in the genetic background of different ethnic populations [69].…”

Claudin 5 Transcripts Following Acrolein Exposure Affected by Epigenetic Enzyme

“…DNMT3A and DNMT3B initiate de-novo methylation [7], although the triggers for this activity are only partly identified. Age, sex, genetic polymorphisms, and environmental exposures are some factors associated with altered methylation [8]. Histones can be modified by a number of processes including by acetylation, phosphorylation, methylation, ubiquitination or sumoylation [5].…”