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


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
SNP-43 of CAPN10 may contribute to the risk of diabetes by regulating abdominal obesity in subjects with high risk of type 2 diabetes.
Pihlajamäki
J
J
University of Kuopio, Department of Medicine, Kuopio, Finland. Jussi.Pihlajamaki@joslin.harvard.edu
Salmenniemi
U
U
Vänttinen
M
M
Ruotsalainen
E
E
Kuusisto
J
J
Vauhkonen
I
I
Kainulainen
S
S
Ng
M C Y
MC
Cox
N J
NJ
Bell
G I
GI
Laakso
M
M
D050153:Abdominal Fat; D000328:Adult; D000368:Aged; D002154:Calpain / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
D002154:Calpain; C415197:calpain 10