Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function

J Clin Invest. 1997 Dec 15;100(12):3005-13. doi: 10.1172/JCI119854.


Catecholamines play a central role in the regulation of energy expenditure, in part by stimulating lipid mobilization through lipolysis in fat cells. The beta-2 adrenoceptor (BAR-2) is a major lipolytic receptor in human fat cells. To determine whether known polymorphisms in codons 16, 27, and 164 of this receptor play a role in obesity and subcutaneous adipocyte BAR-2 lipolytic function, we investigated a group of 140 women with a large variation in body fat mass. Only the polymorphisms in codons 16 and 27 were common in the study population. The Gln27Glu polymorphism was markedly associated with obesity with a relative risk for obesity of approximately 7 and an odds ratio of approximately 10. Homozygotes for Glu27 had an average fat mass excess of 20 kg and approximately 50% larger fat cells than controls. However, no significant association with changes in BAR-2 function was observed. The Arg16Gly polymorphism was associated with altered BAR-2 function with Gly16 carriers showing a fivefold increased agonist sensitivity and without any change in BAR-2 expression. However, it was not significantly linked with obesity. These findings suggest that genetic variability in the human BAR-2 gene could be of major importance for obesity, energy expenditure, and lipolytic BAR-2 function in adipose tissue, at least in women.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Adult
  • Codon
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Obesity / genetics*
  • Obesity / metabolism
  • Phenotype
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Receptors, Adrenergic, beta-2 / genetics*
  • Receptors, Adrenergic, beta-2 / metabolism*


  • Codon
  • Receptors, Adrenergic, beta-2