Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function.
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.
Large
V
V
Department of Medicine, and Research Center, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Hellström
L
L
Reynisdottir
S
S
Lönnqvist
F
F
Eriksson
P
P
Lannfelt
L
L
Arner
P
P
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D003062:Codon; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism*
D003062:Codon; D018343:Receptors, Adrenergic, beta-2