Influence of β 2-adrenoceptor gene polymorphisms on β 2-adrenoceptor expression in human lung

Abstract

Background The aim of the present study was to establish whether polymorphisms, especially those within the promoter region, of the β 2-adrenoceptor gene ( ADRB2) influence β 2-adrenoceptor expression in human lung. Methods The density of β-adrenoceptors in human lung tissue ( n = 88) was determined by saturation binding using the radioligand, iodinated cyanopindolol. Discrimination of β 1- and β 2-adrenoceptors was determined using the highly selective β 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 β 2-adrenoceptor expression were investigated. Results The density of β 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 β 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 β 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 β 2-adrenoceptor expression in human lung.