Influence of beta2-adrenoceptor gene polymorphisms on beta2-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 177fmol/mg protein (mean+/-S.E.M., 72+/-4fmol/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+/-15fmol/mg protein; n=5) expressed significantly (P=0.0005) higher levels of beta(2)-adrenoceptor than those that were homozygous (69+/-4fmol/mg protein; n=83).


CONCLUSIONS
With the exception of position 491, these data indicate that polymorphisms of ADRB2 do not influence beta(2)-adrenoceptor expression in human lung.
Kay
Linda J
LJ
Academic Unit of Respiratory Medicine, University of Sheffield, The Medical School (Floor M), Beech Hill Road, Sheffield S10 2RX, UK.
Suvarna
S Kim
SK
Scola
Anne-Marie
AM
Rostami-Hodjegan
Amin
A
Chess-Williams
Russell
R
Peachell
Peter T
PT
D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011869:Radioligand Assay; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2; C047975:cyanopindolol; D010869:Pindolol