Family-based association analysis of beta2-adrenergic receptor polymorphisms in the childhood asthma management program.
BACKGROUND
Beta2-adrenergic receptor (B2AR) polymorphisms have been associated with a variety of asthma-related phenotypes, but association results have been inconsistent across different studies.


OBJECTIVE
We sought to apply family-based association methods to individual single nucleotide polymorphisms (SNPs) and haplotypes of SNPs in B2AR to define the relationship of these genetic variants to asthma-related phenotypes.


METHODS
DNA samples were obtained from 707 Childhood Asthma Management Program participants, representing 650 sibships, as well as their parents. Genotyping was performed at 8 B2AR SNPs. Qualitative asthma-related phenotypes were analyzed with single SNPs and haplotypes by using TRANSMIT; quantitative asthma-related phenotypes were analyzed with the Family-Based Association Test.


RESULTS
Several SNPs, including SNP -654 and SNP +46, demonstrated significant associations (P <.05) to postbronchodilator FEV1 as both a qualitative (<80% of predicted value) and quantitative phenotype. Quantitative phenotypic association analysis demonstrated significant evidence for association of SNP +523 with bronchodilator responsiveness expressed as a percentage of baseline FEV1 (P =.012) or a percentage of predicted FEV1 (P =.008). Similar evidence for association between the +523 SNP and qualitative bronchodilator responsiveness phenotypes was also found. Analysis of haplotypes supported an association of B2AR variants with spirometric values and bronchodilator responsiveness.


CONCLUSIONS
B2AR variants are associated with spirometric values and bronchodilator responsiveness, but different regions of the gene provide evidence for association with these phenotypes.
Silverman
Edwin K
EK
Channing Laboratory, Brigham and Women's Hospital, Boston, Mass 02115, USA.
Kwiatkowski
David J
DJ
Sylvia
Jody S
JS
Lazarus
Ross
R
Drazen
Jeffrey M
JM
Lange
Christoph
C
Laird
Nan M
NM
Weiss
Scott T
ST
D000483:Alleles; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000627:therapeutic use; D005541:Forced Expiratory Volume; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D013147:Spirometry
D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2