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

研究成果: Article査読

21 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号e0129385
ジャーナルPloS one
10
6
DOI
出版ステータスPublished - 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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