Common polymorphisms of calpain-10 are associated with abdominal obesity in subjects at high risk of type 2 diabetes

• Published in: Diabetologia 2006-07, Vol.49 (7), p.1560-1566
• Main Authors: PIHIAJAMAKI, J, SALMENNIEMI, U, LAAKSO, M, VÄNTTINEN, M, RUOTSALAINEN, E, KUUSISTO, J, VAUHKONEN, I, KAINULAINEN, S, NG, M. C. Y, COX, N. J, BELL, G. I
• Format: Article
• Language: English
• Subjects: Abdomen; Abdominal Fat; Adult; Aged; Biological and medical sciences; Calpain - genetics; Cardiovascular disease; Diabetes; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Finland; Genetic Predisposition to Disease; Glucose; Glucose Tolerance Test; Haplotypes; Humans; Insulin resistance; Linkage Disequilibrium; Male; Medical sciences; Middle age; Middle Aged; Obesity; Obesity - genetics; Oxidation; Polymorphism; Polymorphism, Single Nucleotide; Risk
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-006-0270-z

The mechanisms by which the calpain-10 gene (CAPN10) affects the risk of type 2 diabetes are unclear. Therefore, we investigated the effects of four polymorphisms in CAPN10 (single nucleotide polymorphism [SNP]-43, SNP-44, Insertion/Deletion [Indel]-19 and SNP-63) on insulin secretion, insulin action and abdominal fat distribution in offspring of patients with type 2 diabetes. Insulin secretion was determined by an IVGTT, insulin action by the hyperinsulinaemic-euglycaemic clamp and abdominal fat distribution by computed tomography in 158 non-diabetic offspring (age 34.9+/-6.3 years [mean+/-SD], BMI 26.2+/-4.9 kg/m(2)) of type 2 diabetic patients. SNP-43 (p=0.009 over the three genotypes, adjusted for age, sex, BMI and family relationship) and haplotypes carrying the A allele of SNP-43 were associated with intra-abdominal fat area. The A allele of SNP-43 was associated with intra-abdominal fat area in men (p=0.014) but not in women. SNP-44, InDel-19 and SNP-63 were not associated with intra-abdominal fat area or insulin action. Furthermore, we demonstrated in a separate sample of middle-aged men (n=234) who had a history of type 2 diabetes in first-degree relatives that the A allele of SNP-43 was associated with a large waist circumference, and high insulin levels in an OGTT. SNP-43 of CAPN10 may contribute to the risk of diabetes by regulating abdominal obesity in subjects with high risk of type 2 diabetes.