title: Calpain-10 gene polymorphism is associated with reduced beta(3)-adrenoceptor function in human fat cells.
abstract: Polymorphism in the calpain-10 gene is linked to type 2 diabetes, insulin resistance, and decreased thermogenesis. In view of the role of beta-adrenoceptors in thermogenesis we investigated the relationship between beta(1)-, beta(2)-, and beta(3)-adrenoceptor-stimulated lipolysis in abdominal sc fat cells and 3 different previously described single nucleotide polymorphisms (SNPs) in the calpain-10 gene (SNP-19, SNP-43, and SNP-63). The study sample comprised 240 healthy subjects. A strong association between lipolytic beta(3)-receptor function in adipocytes and the SNP-19, which is a deletion/insertion (1/2) was observed in overweight subjects (body mass index, >25 kg/m(2)), but not in lean ones. No association was found between any of the polymorphisms and lipolytic function of either beta(1)- or beta(2)-receptors. Carriers of 1/1 in SNP-19 had 30-fold decreased lipolytic sensitivity of beta(3)-adrenoceptors in comparison to 1/2 or 2/2 carriers (P = 0.0019, by ANOVA). This was found in both genders and was not influenced by SNP-43 or SNP-63 in the calpain-10 gene or by the Trp(64)Arg polymorphism in the beta(3)-adrenoceptor gene. In conclusion, a deletion/insertion polymorphism in the calpain-10 gene (SNP-19) is associated with reduced beta(3)-adrenoceptor function in obesity. This could be of importance for regulating thermogenesis in overweight subjects.
authors.affiliation: Department of Medicine, Huddinge University Hospital, Karolinska Institute, SE-141 86 Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Hoffstedt
authors.forename: Erik
authors.initials: E
authors.lastname: Näslund
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D002154:Calpain / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008066:Lipolysis; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology*; D011110:Polymorphism, Genetic / Q000502:physiology*; D011412:Propanolamines / Q000494:pharmacology; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology*
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3; D002154:Calpain; C415197:calpain 10; C033394:CGP 12177