• Elliot Israel, Jessica Lasky-Su, Amy Markezich, Amy Damask, Stanley J Szefler, Brooke Schuemann, Barbara Klanderman, Jody Sylvia, Shamsah Kazani, Rongling Wu, Fernando Martinez, Homer A Boushey, Vernon M Chinchilli, Dave Mauger, Scott T Weiss, Kelan G Tantisira, and SHARP Investigators.
• 1 Division of Pulmonary and Critical Care Medicine and.
• Am. J. Respir. Crit. Care Med. 2015 Mar 1; 191 (5): 530-7.

Rationaleβ2-Agonists are the most common form of treatment of asthma, but there is significant variability in response to these medications. A significant proportion of this responsiveness may be heritable.ObjectivesTo investigate whether a genome-wide association study (GWAS) could identify novel pharmacogenetic loci in asthma.MethodsWe performed a GWAS of acute bronchodilator response (BDR) to inhaled β2-agonists. A total of 444,088 single-nucleotide polymorphisms (SNPs) were examined in 724 individuals from the SNP Health Association Resource (SHARe) Asthma Resource Project (SHARP). The top 50 SNPs were carried forward to replication in a population of 444 individuals.Measurements And Main ResultsThe combined P value for four SNPs reached statistical genome-wide significance aftercorrecting for multiple comparisons. Combined P values for rs350729, rs1840321, rs1384918, and rs1319797 were 2.21 × 10(-10), 5.75 × 10(-8), 9.3 × 10(-8), and 3.95 × 10(-8), respectively. The significant variants all map to a novel genetic region on chromosome 2 near the ASB3 gene, a region associated with smooth muscle proliferation. As compared with the wild type, the presence of the minor alleles reduced the degree of BDR by 20% in the original population and by a similar percentage in the confirmatory population.ConclusionsThese GWAS findings for BDR in subjects with asthma suggest that a gene associated with smooth muscle proliferation may influence a proportion of the smooth muscle relaxation that occurs in asthma.

35 keywords...

hide…