BETA(2)-ADRENERGIC RECEPTOR HAPLOTYPES IN MILD, MODERATE AND FATAL NEAR-FATAL ASTHMA

Excess beta(2)-agonist use in asthmatics has been associated with incr eased mortality and morbidity. The mechanisms responsible for these ob servations are unknown. We hypothesized that polymorphisms of the beta (2)-adrenergic receptor (beta(2)AR) at amino acid positions 16, 27, an d 164, which are known to alter receptor functions in vitro, may predi spose asthmatics to fatal/near-fatal asthma and/or modify asthma sever ity. 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(2)A R genotyping was performed on DNA from Caucasians classified as nonast hmatic/nonatopic (n = 84), fatal/near-fatal asthmatics (n = 81) and mi ld/moderate asthmatics (n = 86). No polymorphism or haplotype was foun d to be associated with fatal/near-fatal asthma. However, the Gly16/Gl n27 haplotype, which undergoes enhanced downregulation in vitro, was s ubstantially more prevalent in moderate asthmatics than in mild asthma tics (p = 0.003, odds ratio = 3.1). We conclude that the beta(2)AR gen otype is not a major determinant of fatal or near-fatal asthma. Furthe rmore, allele frequency variation among ethnic groups must be consider ed in clinical studies of beta(2)AR polymorphisms in asthma.