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The Clinical Relevance of Asthma Genetics
There different approaches have been attempted to elucidate the genetic basis of asthma and
other complex diseases. Initially, most studies consisted of assessment of association between
polymorphisms in candidate genes and asthma and asthma-related traits. These studies
provided replicated evidence for association in many different genes (1). Simultaneously, other
studies applied a second approach, namely, linkage analysis between asthma and highly
polymorphic markers distributed in a roughly uniform way in the genome. Although these latter
studies yielded some promising results (2), they proved relatively insensitive to identifying areas
of the genome in which there was clear evidence of the presence of asthma-related genetic
During the last 5 years, the advent of a third phase was received with great enthusiasm by the
scientific community. The availability of hundreds of thousands of single nucleotide
polymorphisms distributed in all human chromosomes opened the possibility to assess direct
associations between these markers (and implicitly those in linkage disequilibrium with them)
and asthma. As a result of these major technical advances, a number of major genome-wide
association studies (GWAS) of asthma have been published (3). These studies have identified
several new genes with polymorphisms that are associated with asthma in a highly replicable
manner, but still, only a small fraction of the genetic variance of asthma is explained by these
GWAS-discovered polymorphisms. With few exceptions (e.g., IL-13), these studies have been
unable to replicate most of the associations reported in candidate genes during the first phase.
Moreover, most of the genetic variants associated with asthma are very common in the
population, and their sensitivity and specificity are too low to allow their use in clinical practice to
predict asthma risk.
Of great interest to the practicing clinician would also be genetic variants associated with
response to therapy, and there have been advances is this area as well, with polymorphisms
having been identified that predict response to inhaled corticosteroids. Unfortunately, the
previously reported associations between the Arg/Gly locus in the beta-2-adrenergic gene and
response to short-acting and long acting beta-agonists have been replicated with variable
success and are not likely to provide clinically important information.
All in all, identified associations between asthma and common genetic polymorphisms have
increased our understanding of the biological mechanisms involved in asthma pathogenesis, but
have yet to provide us with new tools for asthma diagnosis or personalized treatment.
1. Vercelli D. Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol. 2008
2. Denham S, Koppelman GH, Blakey J, Wjst M, Ferreira MA, Hall IP, Sayers I. Meta-analysis
of genome-wide linkage studies of asthma and related traits. Respir Res. 2008 Apr 28;9:38
3. March ME, Sleiman PM, Hakonarson H. The genetics of asthma and allergic disorders.
Discov Med. 2011 Jan;11(56):35-4