Genetics of Asthma and Bronchial Hyperresponsiveness

  • Matthew J. Rose-Zerilli
  • John W. Holloway
  • Stephen T. Holgate
Part of the Allergy Frontiers book series (ALLERGY, volume 1)

Asthma is a polygenic disease differentially modulated by heterogeneous gene—environment and gene—gene interactions. For the last two decades, considerable effort has been made to identify the precise genetic factors that lead to susceptibility to this disease. Identification of these factors has advanced our understanding of this disease and has lead to targets for the development of novel therapies to treat patients. The benefits of genetic approaches to study disease mechanisms are exemplified by the recent advances in the understanding of the pathophysiology of other common diseases such as cardiovascular disease and diabetes [1–4] and which are now beginning to have an impact on patient treatment [5–7]. These studies give us insight into the likely outcome of recent and future studies of the genetic basis of asthma.

The recent advances in the understanding of the genetics of asthma and the related phenotype bronchial hyperresponsiveness (BHR) have been driven by successful positional cloning and candidate gene association studies whose aim was to identify genetic factors that underpin inter-patient variability in susceptibility. Since the identification of the first genomic region on Chromosome (Chr) 11 with linkage to an asthma related phenotype by Cookson et al. [8] in 1989, there have been numerous asthma and BHR susceptibility loci found by these approaches [9]. The Online Mendelian Inheritance in Man website ( lists under the search term: Asthma, susceptibility to (#600807), loci on chromosomes 2, 4, 5, 6, 10, 11 and 13 and a search for BHR reveals additional reported linkage to regions on chromosomes 1, 2, 7, 14. All of these loci are likely to contain one or possibly more genes in which variation may play a small but important role in asthma susceptibility. As a consequence, diligent work to elucidate the precise genetic variations and how these variations contribute to the pathogenesis of this disease will be required. Furthermore this highlights the numerous challenges that researchers face in completely understanding the role of genetic variation in asthma. However, despite these difficulties, there has been considerable progress in the last 5 years in identifying novel genes that underlie these peaks of linkage [10–12]. This progress is likely to be accelerated in the coming months and years as the novel approach of whole genome association (WGA) studies is applied to asthma [13].


Single Nucleotide Polymorphism Allergy Clin Immunol Respir Crit Environmental Tobacco Smoke Bronchial Hyperresponsiveness 
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Copyright information

© Springer 2009

Authors and Affiliations

  • Matthew J. Rose-Zerilli
    • 1
  • John W. Holloway
    • 1
  • Stephen T. Holgate
    • 2
  1. 1.Divisions of Human Genetics and Infection, Inflammation and RepairUniversity of Southampton, School of Medicine, Southampton General HospitalSouthamptonUK
  2. 2.Divisions of Infection, Inflammation and RepairUniversity of Southampton, School of Medicine, Southampton General HospitalSouthamptonUk

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