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. CONCLUSION: B2AR variants are associated with spirometric values and bronchodilator responsiveness, but different regions of the gene provide evidence for association with these phenotypes.
RCT Entities:
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. CONCLUSION:B2AR variants are associated with spirometric values and bronchodilator responsiveness, but different regions of the gene provide evidence for association with these phenotypes.
Authors: Katherine A Drake; Dara G Torgerson; Christopher R Gignoux; Joshua M Galanter; Lindsey A Roth; Scott Huntsman; Celeste Eng; Sam S Oh; Sook Wah Yee; Lawrence Lin; Carlos D Bustamante; Andrés Moreno-Estrada; Karla Sandoval; Adam Davis; Luisa N Borrell; Harold J Farber; Rajesh Kumar; Pedro C Avila; Emerita Brigino-Buenaventura; Rocio Chapela; Jean G Ford; Michael A Lenoir; Fred Lurmann; Kelley Meade; Denise Serebrisky; Shannon Thyne; William Rodríguez-Cintrón; Saunak Sen; José R Rodríguez-Santana; Ryan D Hernandez; Kathleen M Giacomini; Esteban G Burchard Journal: J Allergy Clin Immunol Date: 2013-08-29 Impact factor: 10.793
Authors: Gregory A Hawkins; Kelan Tantisira; Deborah A Meyers; Elizabeth J Ampleford; Wendy C Moore; Barbara Klanderman; Stephen B Liggett; Stephen P Peters; Scott T Weiss; Eugene R Bleecker Journal: Am J Respir Crit Care Med Date: 2006-08-24 Impact factor: 21.405
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Authors: Alfredo Panebra; Mary Rose Schwarb; Clare B Glinka; Stephen B Liggett Journal: Am J Respir Cell Mol Biol Date: 2007-01-25 Impact factor: 6.914
Authors: Ann Chen Wu; Blanca E Himes; Jessica Lasky-Su; Augusto Litonjua; Stephen P Peters; John Lima; Michiaki Kubo; Mayumi Tamari; Yusuke Nakamura; Weiliang Qiu; Scott T Weiss; Kelan Tantisira Journal: J Allergy Clin Immunol Date: 2013-11-23 Impact factor: 10.793
Authors: Victor E Ortega; Gregory A Hawkins; Stephen P Peters; Eugene R Bleecker Journal: Immunol Allergy Clin North Am Date: 2007-11 Impact factor: 3.479