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

Diabetologia. 2006 Jul;49(7):1560-6. doi: 10.1007/s00125-006-0270-z. Epub 2006 May 12.


Aims/hypothesis: 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.

Subjects and methods: 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.

Results: 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.

Conclusions/interpretation: SNP-43 of CAPN10 may contribute to the risk of diabetes by regulating abdominal obesity in subjects with high risk of type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Fat*
  • Adult
  • Aged
  • Calpain / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Finland
  • Genetic Predisposition to Disease*
  • Glucose Tolerance Test
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide*
  • Risk


  • Calpain
  • calpain 10