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beta(2)-adrenergic receptor promoter haplotype influences spirometric response during an acute asthma exacerbation.

Authors: Moore, PE  Williams, SM  Gebretsadik, T  Jiang, L  Minton, PL  Shintani, A  Phillips Iii, JA  Dawson, EP  Hartert, TV 
Citation: Moore PE, etal., Clin Transl Sci. 2008 Sep;1(2):155-61.
Pubmed: (View Article at PubMed) PMID:20443840
DOI: Full-text: DOI:10.1111/j.1752-8062.2008.00036.x

Genetic variants in the beta(2)-adrenergic receptor (ADRB2) coding block have been associated with different parameters of asthma severity, but there is no consensus on which variants are most important. Our objective was to determine whether the genetic variants in the 5'- or 3'-flanking regions of ADRB2 impact the response to therapy. DNA was obtained initially from 72 adults hospitalized for an asthma exacerbation. We sequenced a 5,000 bp region of the ADRB2 gene that spanned the flanking regions and identified 31 single nucleotide polymorphisms (SNPs). Nonresponders to asthma therapy were defined as patients whose forced expiratory volume in 1 second (FEV(1)) worsened by >10% at 24 hours after admission. We then evaluated the relationship between the 19 common SNPs and response to asthma-specific therapy during acute disease exacerbations. Our results showed a significant association between nonresponders and a haplotype of five promoter SNPs in a nearly complete linkage disequilibrium. An analysis of the promoter and coding block polymorphisms in an extended cohort of 99 patients confirmed that promoter haplotype was the genetic component most strongly associated with asthmatic nonresponders, which was statistically significant among whites (p < 0.05). An identification of this promoter haplotype may provide an alternate explanation for the variation in the asthma responses observed with ADRB2 coding block polymorphisms.

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CRRD Object Information
CRRD ID: 4145108
Created: 2010-10-25
Species: All species
Last Modified: 2010-10-25
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.