Genome-Wide Association Study Identifies Novel Pharmacogenomic Loci For Therapeutic Response to Montelukast in Asthma

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Genome-Wide Association Study Identifies Novel Pharmacogenomic Loci For Therapeutic Response to Montelukast in Asthma

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Title: Genome-Wide Association Study Identifies Novel Pharmacogenomic Loci For Therapeutic Response to Montelukast in Asthma
Author: Dahlin, Amber; Litonjua, Augusto; Lima, John J.; Tamari, Mayumi; Kubo, Michiaki; Irvin, Charles G.; Peters, Stephen P.; Tantisira, Kelan G.

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Citation: Dahlin, Amber, Augusto Litonjua, John J. Lima, Mayumi Tamari, Michiaki Kubo, Charles G. Irvin, Stephen P. Peters, and Kelan G. Tantisira. 2015. “Genome-Wide Association Study Identifies Novel Pharmacogenomic Loci For Therapeutic Response to Montelukast in Asthma.” PLoS ONE 10 (6): e0129385. doi:10.1371/journal.pone.0129385. http://dx.doi.org/10.1371/journal.pone.0129385.
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Abstract: Background: Genome-wide association study (GWAS) is a powerful tool to identify novel pharmacogenetic single nucleotide polymorphisms (SNPs). Leukotriene receptor antagonists (LTRAs) are a major class of asthma medications, and genetic factors contribute to variable responses to these drugs. We used GWAS to identify novel SNPs associated with the response to the LTRA, montelukast, in asthmatics. Methods: Using genome-wide genotype and phenotypic data available from American Lung Association - Asthma Clinical Research Center (ALA-ACRC) cohorts, we evaluated 8-week change in FEV1 related to montelukast administration in a discovery population of 133 asthmatics. The top 200 SNPs from the discovery GWAS were then tested in 184 additional samples from two independent cohorts. Results: Twenty-eight SNP associations from the discovery GWAS were replicated. Of these, rs6475448 achieved genome-wide significance (combined P = 1.97 x 10-09), and subjects from all four studies who were homozygous for rs6475448 showed increased ΔFEV1 from baseline in response to montelukast. Conclusions: Through GWAS, we identified a novel pharmacogenomic locus related to improved montelukast response in asthmatics.
Published Version: doi:10.1371/journal.pone.0129385
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470685/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:17295771
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