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Nov/Dec 2000
Vol. 3, No. 9, p. 17.

news in brief

Predicting asthma drug response

Opening ArtWith the rapid databasing of single nucleotide polymorphisms (SNPs), the day is swiftly approaching when a genetic test will determine whether a specific drug should be prescribed for a particular ailment. For the treatment of asthma, that day may already be here.

Connie Drysdale and her colleagues at Genaissance Pharmaceuticals, Inc., in New Haven, CT, and the University of Cincinnati College of Medicine have looked for a correlation between SNPs in the β2-adrenergic receptor (β2AR) gene and the response to albuterol, a β-agonist and asthma drug (Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 10483–10488). A member of the family of G protein-coupled receptors, β2AR mediates the action of catecholamines in various tissues.

The group first defined 12 genetic haplotypes (a group of SNPs or alleles that are closely linked) among a large population of asthmatics by determining the presence or absence of various β2AR SNPs. They then generated a phylogenetic tree and determined the prevalence of specific haplotypes within the studied population and four subgroups—Caucasian, African American, Hispanic–Latino, and Asian. Patients carrying combinations (diplotypes: 2 genes per individual) of the three most prevalent haplotypes—2, 4, and 6— were then examined for their response to albuterol.

Individuals with the diplotype 2/2 had a higher drug response than those carrying 2/4 and a significantly higher response (twofold) than those carrying 4/4. This suggested that the 4 diplotype somehow down-regulated the albuterol response. As a further support, the researchers transfected the genes into cell cultures to determine β2AR mRNA and protein levels. Not surprisingly, cells carrying the 2 haplotype had twice the β2AR mRNA and almost twice the protein of cells carrying the 4 haplotype. (Unfortunately, there were no 6/6 individulas in the study, and thus, interpretation of the 6 haplotype is incomplete.)

“We’ve known for some time that some [patients] respond very well to asthma medications and some do not,” said Stephen Liggett, the group’s principal investigator. “Ultimately,” he adds, “a patient will be able to come to a physician’s office . . . and a genetic panel of haplotype markers can be obtained that will give the physician a readout of the likelihood or probability of the patient responding to all of the commonly utilized drugs in the treatment of that disease.”


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