Calpain-10 Gene Polymorphism Is Associated with Reduced ß3-Adrenoceptor Function in Human Fat Cells
Johan Hoffstedt,
Erik Näslund and
Peter Arner
Department of Medicine, Huddinge University Hospital, and Department of Surgery, Danderyd Hospital (E.N.), Karolinska Institute, SE-141 86 Stockholm, Sweden
Address all correspondence and requests for reprints to: Dr. Peter Arner, Department of Medicine, M63, Huddinge University Hospital, SE-141 86 Stockholm, Sweden. E-mail: . peter.arner{at}medhs.ki.se
Abstract
Polymorphism in the calpain-10 gene is linked to type 2 diabetes,insulin resistance, and decreased thermogenesis. In view ofthe role of ß-adrenoceptors in thermogenesis we investigatedthe relationship between ß1-, ß2-, and ß3-adrenoceptor-stimulatedlipolysis in abdominal sc fat cells and 3 different previouslydescribed single nucleotide polymorphisms (SNPs) in the calpain-10gene (SNP-19, SNP-43, and SNP-63). The study sample comprised240 healthy subjects. A strong association between lipolyticß3-receptor function in adipocytes and the SNP-19,which is a deletion/insertion (1/2) was observed in overweightsubjects (body mass index, >25 kg/m2), but not in lean ones.No association was found between any of the polymorphisms andlipolytic function of either ß1- or ß2-receptors.Carriers of 1/1 in SNP-19 had 30-fold decreased lipolytic sensitivityof ß3-adrenoceptors in comparison to 1/2 or 2/2 carriers(P = 0.0019, by ANOVA). This was found in both genders and wasnot influenced by SNP–43 or SNP–63 in the calpain-10gene or by the Trp64Arg polymorphism in the ß3-adrenoceptorgene. In conclusion, a deletion/insertion polymorphism in thecalpain-10 gene (SNP-19) is associated with reduced ß3-adrenoceptorfunction in obesity. This could be of importance for regulatingthermogenesis in overweight subjects.
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