TY - JOUR
T1 - The -866A/A genotype in the promoter of the human uncoupling protein 2 gene is associated with insulin resistance and increased risk of type 2 diabetes
AU - D'Adamo, Monica
AU - Perego, Lucia
AU - Cardellini, Marina
AU - Marini, Maria Adelaide
AU - Frontoni, Simona
AU - Andreozzi, Francesco
AU - Sciacqua, Angela
AU - Lauro, Davide
AU - Sbraccia, Paolo
AU - Federici, Massimo
AU - Paganelli, Michele
AU - Pontiroli, Antonio E.
AU - Lauro, Renato
AU - Perticone, Francesco
AU - Folli, Franco
AU - Sesti, Giorgio
PY - 2004/7
Y1 - 2004/7
N2 - Uncoupling protein (UCP)-2 is a member of the mitochondrial inner membrane carriers that uncouple proton entry in the mitochondrial matrix from ATP synthesis. The -866G/A polymorphism in the UCP2 gene, which enhances its transcriptional activity, was associated with enhanced risk for type 2 diabetes in obese subjects. We addressed the question of whether the -866G/A polymorphism contributes to variation in insulin sensitivity by genotyping 181 nondiabetic offspring of type 2 diabetic patients. Insulin sensitivity, assessed by the hyperinsulinemic-euglycemic clamp, was reduced in -866A/A carriers compared with -866A/G or -866G/G carriers (P = 0.01). To directly investigate the correlation between UCP2 expression and insulin resistance, UCP2 mRNA levels were measured by real-time RT-PCR in subcutaneous fat obtained from 100 obese subjects who underwent laparoscopic adjustable gastric banding. UCP2 mRNA expression was significantly correlated with insulin resistance as assessed by the homeostasis model assessment index (r = 0.27, P = 0.007). We examined the association of the -866A/A genotype in a case-control study including 483 type 2 diabetic subjects and 565 control subjects. The -866A/A genotype was associated with diabetes in women (odds ratio 1.84, 95% CI 1.03-3.28; P = 0.037), but not in men. These results indicate that the -866A/A genotype of the UCP2 gene may contribute to diabetes susceptibility by affecting insulin sensitivity.
AB - Uncoupling protein (UCP)-2 is a member of the mitochondrial inner membrane carriers that uncouple proton entry in the mitochondrial matrix from ATP synthesis. The -866G/A polymorphism in the UCP2 gene, which enhances its transcriptional activity, was associated with enhanced risk for type 2 diabetes in obese subjects. We addressed the question of whether the -866G/A polymorphism contributes to variation in insulin sensitivity by genotyping 181 nondiabetic offspring of type 2 diabetic patients. Insulin sensitivity, assessed by the hyperinsulinemic-euglycemic clamp, was reduced in -866A/A carriers compared with -866A/G or -866G/G carriers (P = 0.01). To directly investigate the correlation between UCP2 expression and insulin resistance, UCP2 mRNA levels were measured by real-time RT-PCR in subcutaneous fat obtained from 100 obese subjects who underwent laparoscopic adjustable gastric banding. UCP2 mRNA expression was significantly correlated with insulin resistance as assessed by the homeostasis model assessment index (r = 0.27, P = 0.007). We examined the association of the -866A/A genotype in a case-control study including 483 type 2 diabetic subjects and 565 control subjects. The -866A/A genotype was associated with diabetes in women (odds ratio 1.84, 95% CI 1.03-3.28; P = 0.037), but not in men. These results indicate that the -866A/A genotype of the UCP2 gene may contribute to diabetes susceptibility by affecting insulin sensitivity.
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U2 - 10.2337/diabetes.53.7.1905
DO - 10.2337/diabetes.53.7.1905
M3 - Article
C2 - 15220218
AN - SCOPUS:3042698328
VL - 53
SP - 1905
EP - 1910
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 7
ER -