ORIGINAL ARTICLE

ß₂ adrenoceptor promoter polymorphisms: extended haplotypes and functional effects in peripheral blood mononuclear cells

B Lipworth¹, G H Koppelman³, A P Wheatley², I Le Jeune², W Coutie¹, H Meurs⁴, H F Kauffman⁵, D S Postma³, I P Hall²

¹ Asthma and Allergy Research Group, Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
² Division of Therapeutics, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK
³ Department of Pulmonology, University Hospital Groningen, Groningen, the Netherlands
⁴ Department of Molecular Pharmacology, University Centre for Pharmacy, Groningen
⁵ Department of Allergology, University Hospital Groningen

Correspondence to:
Correspondence to:
Professor I P Hall, Division of Therapeutics, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK;
Ian.hall{at}nottingham.ac.uk

Background: The ß₂ adrenoceptor and its 5' untranslated region contain a number of genetic variants. The aim of this study was to investigate the potential for genetic variation at this locus to influence the expression of ß₂ adrenoceptors on circulating peripheral blood mononuclear cells (PBMCs).

Methods: Genotype was determined in 96 individuals with asthma for four polymorphisms at the ß₂ adrenoceptor locus. ß₂ adrenoceptor binding and cyclic AMP responses to isoprenaline in PBMCs were determined and the relationship between genotype/haplotype and ß₂ adrenoceptor expression and response to isoprenaline examined.

Results: ß₂ adrenoceptor promoter polymorphisms were found to be common in white subjects. Strong linkage disequilibrium exists across this locus, resulting in the occurrence of several common haplotypes. No single polymorphism or haplotype was correlated with the level of ß₂ adrenoceptor expression or cyclic AMP responses to isoprenaline in vitro.

Conclusion: ß₂ adrenoceptor polymorphisms, when considered in isolation or by extended haplotypes, do not determine the basal level of expression or coupling of ß₂ adrenoceptors in PBMCs from asthmatic subjects.

Keywords: ß₂ adrenoceptor; polymorphism; haplotype; asthma; pharmacogenetics

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