Relationship between beta-2 adrenoceptor gene haplotypes and adipocyte lipolysis in women

BACKGROUND AND AIMS: The beta(2)-adrenergic receptors are important for adipocyte lipolysis regulation by catecholamines in humans. The beta(2)-adrenoceptor gene is highly polymorphic. The role of these genetic variations for adipocyte lipolysis was investigated. DESIGN AND METHODS: Six single-nucleotide polymorphisms (SNPs) in the promotor region and four SNPs in the coding region (leading to amino-acid substitution) of the beta(2)-adrenoceptor gene were determined in 141 overweight or obese, but otherwise healthy women. Lipolysis experiments were performed on isolated subcutaneous adipocytes. RESULTS: Three homozygous haplotypes (6/6, 4/4 and 2/2) were found that differed about 500-fold in noradrenaline sensitivity or beta(2)-adrenoceptor sensitivity (6/6>2/2>4/4, P=0.01). The haplotypes also differed by 100% in maximum noradrenaline-induced lipolysis rates (6/6>2/2>4/4). However, there was no influence on beta(1)-, beta(3)- or alpha(2)A-adrenoceptor sensitivity. Heterozygosity at one or several SNPs in the haplotypes influenced the beta(2)-adrenoceptor sensitivity significantly. CONCLUSION: Multiple SNPs in the beta(2)-adrenoceptor gene form several haplotypes that markedly influence beta(2)-receptor function- and catecholamine-induced lipolysis in fat cells. These haplotypes may be important genetic factors behind impaired lipolysis in obesity.