SNPs pair up in asthma pharmacogenetics
Combinations of SNPs within the beta2-adrenergic receptor gene affect the response to asthma drugs.
Many believe that single nucleotide polymorphisms (SNPs) will prove to be powerful tools as predictive pharmacogenetic loci. In the September 12 Proceedings of the National Academy of Sciences, Drysdale et al. examined the functional significance of SNPs in the 5' upstream and ORF regions of the β2-adrenergic receptor (β2-AR) gene (Proc Natl Acad Sci USA 2000, 97:10483-10488 [abstract]) The β2-ARs are G-protein coupled receptors that can cause muscle relaxation and bronchodilation. Beta-blocker agonists are used as drugs to treat bronchospasms in asthma patients. Drysdale et al. characterized 13 SNPs in the β2-AR gene that were grouped into 12 distinct combinations (haplotypes). They analyzed a group of 121 asthmatics and their response to the beta-blocker albuterol. Pairs of haplotypes were significantly related to drug responsiveness, whereas single SNP haplotypes were not. Furthermore, in vitro transfection experiments showed that SNP haplotypes affect β2-AR expression and receptor density. These results caution against the predictive utility of randomly chosen individual SNP loci, and emphasize the advantage of analyzing multiple SNP combinations simultaneously.