title: Variation in the calpain-10 gene is associated with elevated triglyceride levels and reduced adipose tissue messenger ribonucleic acid expression in obese Swedish subjects.
abstract: Our aim was to investigate the possible role of the type 2 diabetes susceptibility gene CAPN10 in obesity. A case control study consisting of 235 obese Swedish subjects [body mass index, 40 (35-45) kg/m(2)] and 235 controls matched for age and gender [body mass index, 22 (21-24) kg/m(2)], and a transmission disequilibrium test consisting of 116 parents-offspring trios, where the offspring was abdominally obese [waist, 100 (95-110) cm], were performed. CAPN10 mRNA expression was studied in adipose tissue biopsies from 33 of the obese subjects participating in the case control study. The CAPN10 single-nucleotide polymorphism (SNP)-43 was genotyped using PCR followed by NdeI digestion or by allelic discrimination. CAPN10 mRNA levels were quantified using real-time RT-PCR with Cyclophilin A as an internal standard. No significant associations between CAPN10 SNP-43 and obesity were seen, neither in the case control study nor in the transmission disequilibrium test, but obese subjects homozygous for the SNP-43 G allele had significantly elevated triglyceride levels compared with subjects carrying the A allele [1.7 (1.1-2.4) vs. 1.4 (1.0-2.0); P = 0.03]. The CAPN10 mRNA expression in sc fat was significantly reduced in subjects with the SNP-43 G/G genotype compared with carriers of SNP-43 G/A (G/G, 0.33 +/- 0.02, vs. G/A, 0.51 +/- 0.09; P = 0.048), and a similar trend was observed in visceral fat (G/G, 0.52 +/- 0.06, vs. G/A, 0.65 +/- 0.10; P = 0.22). Our data suggest that reduced CAPN10 expression may be a risk factor for features associated with the metabolic syndrome in obese subjects, although variation in the gene does not seem to contribute to the risk for developing obesity per se.
authors.affiliation: Department of Endocrinology, Lund University, Wallenberg Laboratory, Malmö University Hospital, S-205 02 Malmö, Sweden. emma.carlsson@endo.mas.lu.se
authors.forename: Emma
authors.initials: E
authors.lastname: Carlsson
authors.forename: Jenny
authors.initials: J
authors.lastname: Fredriksson
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Martin
authors.initials: M
authors.lastname: Ridderstråle
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000483:Alleles; D002154:Calpain / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism*; D040521:Subcutaneous Tissue / Q000378:metabolism; D013548:Sweden; D014280:Triglycerides / Q000097:blood*; D014781:Viscera / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014280:Triglycerides; D002154:Calpain; C415197:calpain 10