Influence of β2-adrenoceptor gene polymorphisms on β2-adrenoceptor expression in human lung

Background: The aim of the present study was to establish whether polymorphisms, especially those within the promoter region, of the beta(2)-adrenoceptor gene (ADRB2) influence beta(2)-adrenoceptor expression in human lung. Methods: The density of beta-adrenoceptors in human lung tissue (n = 88) was determined by saturation binding using the radioligand, iodinated cyanopindolol. Discrimination of beta(1)- and beta(2)-adrenoceptors was determined using the highly selective (beta(1)-adrenoceptor antagonist, CGP20712A. Genotype was determined at 5 positions of ADRB2 previously reported as polymorphic. Potential influences of single nucleotide polymorphisms (SNPs) within the promoter region (-367, -47) and coding block (46, 79, 491) of ADRB2 on beta(2)-adrenoceptor expression were investigated. Results: The density of beta(2)-adrenoceptors was variable among the 88 lung preparations studied ranging from 17 to 177 fmol/mg protein (mean +/- S.E.M., 72 +/- 4 fmol/mg protein). There was no influence of genotype on beta(2)-adrenoceptor expression for any of the polymorphisms studied except at position 491. The polymorphism at position 491C > T, leading to a change from thr to ile at amino acid 164, is uncommon. Preparations genotyped as heterozygous (126 +/- 15 fmol/mg protein; n = 5) expressed significantly (P = 0.0005) higher levels of beta(2)-adrenoceptor than those that were homozygous (69 +/- 4 fmol/mg protein; n = 83). Conclusion: With the exception of position 491, these data indicate that polymorphisms of ADRB2 do not influence beta(2)-adrenoceptor expression in human lung. (C) Crown Copyright 2009 Published by Elsevier Ltd. All rights reserved.