Mougey E.B.,Asthma Clinical Research Center |
Mougey E.B.,Center for Pharmacogenetics and Translational Research |
Chen C.,Dana-Farber Cancer Institute |
Tantisira K.G.,Harvard University |
And 9 more authors.
Pharmacogenomics Journal | Year: 2013
The interpatient variability in response to asthma controllers is significant and associates with pharmacogenomic variability. The goal of the present study was to identify novel variants that associate with response to common asthma controllers: fluticasone, combination of fluticasone + salmeterol and montelukast with single nucleotide polymorphisms (SNPs) in β2-adrenergic receptor, corticosteroid and leukotriene pathway candidate genes. Participants in a large clinical trial of step-down strategies volunteered for this pharmacogenetic study. A total of 169 SNPs in 26 candidate genes were genotyped in 189 Caucasian participants with asthma who took either fluticasone (100 μg bid), fluticasone propionate (100 μg) + salmeterol (50 μg) (FP/Salm) or montelukast (5 or 10 mg) each night for 16 weeks. Primary outcomes were the slopes of plots of Asthma Control Questionnaire (ACQ) scores versus time following randomization; and the percent change in percent predicted FEV1 (ΔFEV1%pred) from enrollment to the end of the study. Associations between SNPs and outcomes were analyzed using general linear models. False discovery rate and Bonferroni corrections were used to correct for multiple comparisons. In all, 16 SNPs in seven genes were significantly associated with outcomes. For FP/Salm, three SNPs in CHRM2 associated with ACQ slope (P=2.8 × 10-5), and rs1461496 in HSPA8 associated with ΔFEV1%pred. For fluticasone, five SNPs in CRHR1 (P=1.9 × 10 -4), and three SNPs in COL2A1 associated with ACQ slope and ΔFEV1%pred, respectively. For montelukast, four SNPs in CHRM2 associated with ΔFEV1%pred and predicted an opposite effect compared with fluticasone (P=9 × 10-3). The present study indentified several novel SNPs that associate with response to common asthma controllers, and support further pharmacogenomic study and the use of genetic variants to personalize asthma treatment. © 2013 Macmillan Publishers Limited. All rights reserved 1470-269X/13.
Djukanovic R.,University of Southampton |
Hanania N.,Asthma Clinical Research Center |
Busse W.,University of Wisconsin - Madison |
Price D.,University of Aberdeen
Respiratory Medicine | Year: 2016
The central role of IgE in the pathogenesis of allergic asthma has been well established; recent research has brought to light further interesting findings regarding the effects of IgE and anti-IgE therapy. This symposium explored these recent revelations and provided new insights into the importance of IgE in allergic asthma. © 2015 Elsevier Ltd. All rights reserved.
Koshy S.,Baylor College of Medicine |
Huq R.,Baylor College of Medicine |
Tanner M.R.,Baylor College of Medicine |
Atik M.A.,Asthma Clinical Research Center |
And 5 more authors.
Journal of Biological Chemistry | Year: 2014
Background: CCR7+ effector memory T lymphocytes are major players in lung inflammation that characterizes allergic asthma. Results: Blocking KV1.3 channels reduced the severity of an ovalbumin-induced model of asthma in rats. Conclusion: KV1.3 channels are attractive targets for immunomodulation and the treatment of allergic asthma. Significance: Selective KV1.3 channel blockers may prove beneficial in the treatment of asthma. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.