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β2-Adrenergic receptor polymorphisms: pharmacogenetic response to bronchodilator among African American asthmatics

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Abstract

β2-Adrenergic receptor (β2AR) gene polymorphisms have been reported to be associated with various asthma-related traits in different racial/ethnic populations. However, it is unknown whether β 2 AR genetic variants are associated with asthma in African Americans. In this study, we have examined whether there is association between β 2 AR genetic variants and asthma in African Americans. We have recruited 264 African American asthmatic subjects and 176 matched healthy controls participating in the Study of African Americans, Asthma, Genes and Environments (SAGE). We genotyped seven known and recently identified β 2 AR SNP variants, then tested genotype and haplotype association of asthma-related traits with the β 2 AR SNPs in our African American cohort with adjustment of confounding effect due to admixture background and environmental risk factors. We found a significant association of the SNP −47 (Arg-19Cys) polymorphism with ΔFEF25–75, a measure of bronchodilator drug responsiveness, in African American asthmatics after correction for multiple testing (P=0.001). We did not observe association of the SNP +46 (Arg16Gly) variant with asthma disease diagnosis and asthma-related phenotypes. In contrast to previous results between the Arg16Gly variant and traits related to bronchodilator responsiveness, our results indicate that the Arg-19Cys polymorphism in β upstream peptide may play an important role in bronchodilator drug responsiveness in African American subjects. Our findings highlight the importance of investigating genetic risk factors for asthma in different populations.

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Acknowledgements

This work was supported by National Institutes of Health (K23 HL04464, HL07185, GM61390, American Lung Association of California, RWJ Amos Medical Faculty Development Award, NCMHD Health Disparities Scholar, Extramural Clinical Research Loan Repayment Program for Individuals from Disadvantaged Backgrounds, 2001–2003, to EGB), American Lung Association of California (Research Training Fellowship to HJT), U01-HL 65899, UCSF-Children’s Hospital of Oakland Pediatric Clinical Research Center (M01 RR01271), Oakland, CA, Sandler Center for Basic Research in Asthma and the Sandler Family Supporting Foundation. We would like to acknowledge the families and the patients for their participation. We would also like to thank the numerous health care providers for their support and participation in the SAGE Study. Finally, we would like to thank the Sandler Family Foundation, the main sponsor of this project.

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Authors and Affiliations

  1. Department of Medicine, University of California, San Francisco, CA, 94143-0833, USA

    Hui-Ju Tsai, Nishat Shaikh, Jennifer Y. Kho, Natalie Battle, Mariam Naqvi, Daniel Navarro, Henry Matallana, Celeste S. Eng, Gunjan Kumar, Shannon Thyne, Shweta Choudhry & Esteban G. Burchard

  2. Center for Human Genetics, University of California, San Francisco, CA, USA

    Esteban G. Burchard

  3. Lung Biology Center, San Francisco General Hospital, San Francisco, CA, USA

    Esteban G. Burchard

  4. Brigham and Women’s Hospital, Boston, MA, USA

    Craig M. Lilly

  5. The James A. Watson Wellness Center, Oakland, CA, USA

    H. George Watson

  6. Children’s Hospital and Research Institute, Oakland, CA, USA

    Kelley Meade

  7. Bay Area Pediatrics, Oakland, CA, USA

    Michael LeNoir

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  1. Hui-Ju Tsai
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from the Study of African Americans, Asthma, Genes Environments (SAGE)

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Correspondence to Esteban G. Burchard.

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Hui-Ju Tsai and Nishat Shaikh have contributed equally to this manuscript

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Tsai, HJ., Shaikh, N., Kho, J.Y. et al. β2-Adrenergic receptor polymorphisms: pharmacogenetic response to bronchodilator among African American asthmatics. Hum Genet 119, 547–557 (2006). https://doi.org/10.1007/s00439-006-0169-2

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