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

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Kay, L. J., Suvarna, K., Scola, A., Rostami-Hodjegan, A., Chess-Williams, R., & Peachell, P. T. (2009). Influence of β2-adrenoceptor gene polymorphisms on β2-adrenoceptor expression in human lung. Pulmonary pharmacology & therapeutics, 23(2), 71-77.

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2009 HERDC submission. FoR code: 1103; 1115

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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.

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