beta(2) adrenoceptor promoter polymorphisms: extended haplotypes and functional effects in peripheral blood mononuclear cells

B Lipworth, GH Koppelman, AP Wheatley, I Le Jeune, W Coutie, H Meurs, HF Kauffman, DS Postma, IP Hall*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

51 Citaten (Scopus)

Samenvatting

Background: The beta(2) 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 beta(2) adrenoceptors on circulating peripheral blood mononuclear cells (PBMCs).

Methods: Genotype was determined in 96 individuals with asthma for four polymorphisms at the adrenoceptor locus. beta(2) adrenoceptor binding and cyclic AMP responses to isoprenaline in PBMCs were determined and the relationship between genotype/haplotype and beta(2) adrenoceptor expression and response to isoprenaline examined. Results: beta(2) 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 beta(2) adrenoceptor expression or cyclic AMP responses to isoprenaline in vitro.

Conclusion: beta(2) adrenoceptor polymorphisms, when considered in isolation or by extended haplotypes, do not determine the basal level of expression or coupling of beta(2) adrenoceptors in PBMCs from asthmatic subjects.

Originele taal-2English
Pagina's (van-tot)61-66
Aantal pagina's6
TijdschriftThorax
Volume57
Nummer van het tijdschrift1
StatusPublished - jan.-2002

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