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

Pihlajamäki J, Salmenniemi U, Vänttinen M, Ruotsalainen E, Kuusisto J, Vauhkonen I, Kainulainen S, Ng MC, Cox NJ, Bell GI, Laakso M
Diabetologia. 2006 49 (7): 1560-6

PMID: 16752174 · DOI:10.1007/s00125-006-0270-z

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.

MeSH Terms (16)

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

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