Genome-wide association study identifies novel pharmacogenomic loci for therapeutic response to montelukast in Asthma

Amber Dahlin, Augusto Litonjua, John J. Lima, Mayumi Tamari, Michiaki Kubo, Charles G. Irvin, Stephen P. Peters, Kelan G. Tantisira

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21 Citations (Scopus)

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 ΔFEV1from baseline in response to montelukast. Conclusions Through GWAS, we identified a novel pharmacogenomic locus related to improved montelukast response in asthmatics.

Original languageEnglish
Article numbere0129385
JournalPloS one
Volume10
Issue number6
DOIs
Publication statusPublished - 17-06-2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Dahlin, A., Litonjua, A., Lima, J. J., Tamari, M., Kubo, M., Irvin, C. G., Peters, S. P., & Tantisira, K. G. (2015). Genome-wide association study identifies novel pharmacogenomic loci for therapeutic response to montelukast in Asthma. PloS one, 10(6), [e0129385]. https://doi.org/10.1371/journal.pone.0129385