TY - JOUR
T1 - Influence of beta2-adrenoceptor gene polymorphisms on beta2-adrenoceptor expression in human lung
AU - Kay, Linda J.
AU - Suvarna, S. Kim
AU - Scola, Anne Marie
AU - Rostami-Hodjegan, Amin
AU - Chess-Williams, Russell
AU - Peachell, Peter T.
PY - 2010/4
Y1 - 2010/4
N2 - Background: The aim of the present study was to establish whether polymorphisms, especially those within the promoter region, of the β2-adrenoceptor gene (ADRB2) influence β2-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 β1- and β2-adrenoceptors was determined using the highly selective β1-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 β2-adrenoceptor expression were investigated. Results: The density of β2-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 β2-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 β2-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 β2-adrenoceptor expression in human lung. Crown
AB - Background: The aim of the present study was to establish whether polymorphisms, especially those within the promoter region, of the β2-adrenoceptor gene (ADRB2) influence β2-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 β1- and β2-adrenoceptors was determined using the highly selective β1-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 β2-adrenoceptor expression were investigated. Results: The density of β2-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 β2-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 β2-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 β2-adrenoceptor expression in human lung. Crown
UR - http://www.scopus.com/inward/record.url?scp=75749087525&partnerID=8YFLogxK
U2 - 10.1016/j.pupt.2009.10.013
DO - 10.1016/j.pupt.2009.10.013
M3 - Article
C2 - 19887115
AN - SCOPUS:75749087525
SN - 1094-5539
VL - 23
SP - 71
EP - 77
JO - Pulmonary Pharmacology and Therapeutics
JF - Pulmonary Pharmacology and Therapeutics
IS - 2
ER -