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Determination of beta2-adrenergic receptor (ADRB2) haplotypes by a multiplexed polymerase chain reaction assay
Mathew D Littlejohn1, D Robin Taylor, Allison L Miller
1Gene Structure and Function Laboratory, Department of Pathology, Christchurch School of Medicine and Health Sciences, University of Otago, P.O. Box 4345, Christchurch, New Zealand.
Abstract:
The beta2-adrenergic receptor (B2AR or ADRB2) is the target of beta2-agonist drugs used for bronchodilation in asthma and other respiratory diseases. The gene for this receptor (ADRB2) contains numerous single nucleotide polymorphisms (SNPs) some of which may be of pharmacogenetic relevance, although a consistent picture of genotype-phenotype relationships has yet to emerge. Recently, 12 distinct haplotypes of ADRB2were described along with preliminary evidence that certain haplotypes, rather than specific SNPs, determine differential response to the beta-agonist drug albuterol. In order to further evaluate the role of ADRB2haplotypes as pharmacogenetic determinants, simple and accurate methods for haplotyping clinical samples are required. To this end we have developed a multiplexed, allele-specific PCR assay that interrogates six ADRB2 SNPs in a manner that permits rapid and accurate assignment of ADRB2 haplotype pairs. This assay will facilitate studies of ADRB2haplotypes in phenotypes such as patient responses to beta2-agonists, bronchial hyper-responsiveness, and cardiovascular conditions.