Influence of beta2-adrenoceptor gene polymorphisms on beta2-adrenoceptor expression in human lung

Pulm Pharmacol Ther. 2010 Apr;23(2):71-7. doi: 10.1016/j.pupt.2009.10.013. Epub 2009 Nov 1.

Abstract

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).

Conclusion: With the exception of position 491, these data indicate that polymorphisms of ADRB2 do not influence beta(2)-adrenoceptor expression in human lung.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Gene Expression*
  • Genotype
  • Humans
  • Lung / metabolism*
  • Male
  • Pindolol / analogs & derivatives
  • Pindolol / metabolism
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Protein Binding
  • Radioligand Assay
  • Receptors, Adrenergic, beta-2 / genetics*

Substances

  • Receptors, Adrenergic, beta-2
  • cyanopindolol
  • Pindolol