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

Springer Science and Business Media LLC - Tập 119 - Trang 547-557 - 2006
Hui-Ju Tsai1, Nishat Shaikh1, Jennifer Y. Kho1, Natalie Battle1, Mariam Naqvi1, Daniel Navarro1, Henry Matallana1, Craig M. Lilly2, Celeste S. Eng1, Gunjan Kumar1, Shannon Thyne1, H. George Watson3, Kelley Meade4, Michael LeNoir5, Shweta Choudhry1, Esteban G. Burchard1,6,7
1Department of Medicine, University of California, San Francisco, USA
2Brigham and Women’s Hospital, Boston, USA
3The James A. Watson Wellness Center, Oakland, USA
4Children’s Hospital and Research Institute, Oakland, USA
5Bay Area Pediatrics, Oakland, USA
6Center for Human Genetics, University of California, San Francisco, USA
7Lung Biology Center, San Francisco General Hospital, San Francisco, USA

Tóm tắt

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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