Genome-wide association study of leukotriene modifier response in asthma
Irvin, C G
Peters, S P
Lima, J J
Tantisira, K G
MetadataShow full item record
CitationDahlin, A, A Litonjua, C G Irvin, S P Peters, J J Lima, M Kubo, M Tamari, and K G Tantisira. 2016. “Genome-wide association study of leukotriene modifier response in asthma.” The Pharmacogenomics Journal 16 (2): 151-157. doi:10.1038/tpj.2015.34. http://dx.doi.org/10.1038/tpj.2015.34.
AbstractHeterogeneous therapeutic responses to leukotriene modifiers (LTMs) are likely due to variation in patient genetics. Although prior candidate gene studies implicated multiple pharmacogenetic loci, to date, no genome-wide association study (GWAS) of LTM response was reported. In this study, DNA and phenotypic information from two placebo-controlled trials (total N=526) of zileuton response were interrogated. Using a gene–environment (G × E) GWAS model, we evaluated 12-week change in forced expiratory volume in 1 second (ΔFEV1) following LTM treatment. The top 50 single-nucleotide polymorphism associations were replicated in an independent zileuton treatment cohort, and two additional cohorts of montelukast response. In a combined analysis (discovery+replication), rs12436663 in MRPP3 achieved genome-wide significance (P=6.28 × 10−08); homozygous rs12436663 carriers showed a significant reduction in mean ΔFEV1 following zileuton treatment. In addition, rs517020 in GLT1D1 was associated with worsening responses to both montelukast and zileuton (combined P=1.25 × 10−07). These findings implicate previously unreported loci in determining therapeutic responsiveness to LTMs.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:26859907
- HMS Scholarly Articles