Variation in the Calpain-10 Gene Is Associated with Elevated Triglyceride Levels and Reduced Adipose Tissue Messenger Ribonucleic Acid Expression in Obese Swedish Subjects

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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/m2] and 235 controls matched for age and gender [body mass index, 22 (21-24) kg/m2], 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.

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