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Beta2 adrenoceptor promoter polymorphisms: extended haplotypes and functional effects in peripheral blood mononuclear
B Lipworth1, G H Koppelman, A P Wheatley
1Asthma and Allergy Research Group, Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
Background:
The beta2 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 beta2 adrenoceptors on circulating peripheral blood mononuclear cells (PBMCs).
Methods:
Genotype was determined in 96 individuals with asthma for four polymorphisms at the beta2 adrenoceptor locus. Beta2 adrenoceptor binding and cyclic AMP responses to isoprenaline in PBMCs were determined and the relationship between genotype/haplotype and beta2 adrenoceptor expression and response to isoprenaline examined.
Results:
Beta2 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 beta2 adrenoceptor expression or cyclic AMP responses to isoprenaline in vitro.
Conclusion:
Beta2 adrenoceptor polymorphisms, when considered in isolation or by extended haplotypes, do not determine the basal level of expression or coupling of beta2 adrenoceptors in PBMCs from asthmatic subjects.