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Am. J. Respir. Crit. Care Med., Volume 158, Number 3, September 1998, 787-791

beta 2-Adrenergic Receptor Haplotypes in Mild, Moderate and Fatal/Near Fatal Asthma

TRACEY D. WEIR, NOA MALLEK, ANDREW J. SANDFORD, TONY R. BAI, NASSAR AWADH, J. M. FITZGERALD, DON COCKCROFT, ALAN JAMES, STEPHEN B. LIGGETT, and PETER D. PARÉ

Respiratory Health Network of Centres of Excellence, University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver; University of British Columbia Respiratory Division, Vancouver Hospital and Health Sciences Centre, Vancouver; University of Saskatchewan, Royal University Hospital, Saskatoon, Saskachewan; Department of Pulmonary Physiology, Sir Charles Gairdner Hospital, Nedlands, Western Australia; and Division of Pulmonary and Critical Care Medicine, University of Cincinnati, Cinncinatti, Ohio

Excess beta 2-agonist use in asthmatics has been associated with increased mortality and morbidity. The mechanisms responsible for these observations are unknown. We hypothesized that polymorphisms of the beta 2-adrenergic receptor (beta 2AR) at amino acid positions 16, 27, and 164, which are known to alter receptor functions in vitro, may predispose asthmatics to fatal/near-fatal asthma and/or modify asthma severity. In preliminary studies we found significant differences in allele frequencies due to ethnic background: Caucasian, Black, Asian Gly16 = 0.61, 0.50, 0.40 and Gln27 = 0.57, 0.73, 0.80, respectively. beta 2AR genotyping was performed on DNA from Caucasians classified as nonasthmatic/nonatopic (n = 84), fatal/near-fatal asthmatics (n = 81) and mild/moderate asthmatics (n = 86). No polymorphism or haplotype was found to be associated with fatal/near-fatal asthma. However, the Gly16/Gln27 haplotype, which undergoes enhanced downregulation in vitro, was substantially more prevalent in moderate asthmatics than in mild asthmatics (p = 0.003, odds ratio = 3.1). We conclude that the beta 2AR genotype is not a major determinant of fatal or near-fatal asthma. Furthermore, allele frequency variation among ethnic groups must be considered in clinical studies of beta 2AR polymorphisms in asthma.




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