Relationship of the tumor necrosis factor-α −308 A/G promoter polymorphism with insulin sensitivity and abdominal fat distribution in Japanese patients with type 2 diabetes mellitus

Abstract 

We investigated the relationship of the A/G variant of the tumor necrosis factor-α (TNF-α) gene promoter at position −308 with insulin resistance and abdominal fat distribution in type 2 diabetic patients in the Japanese population. The TNF-α polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism in 142 healthy volunteers and 132 type 2 diabetic patients. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) index in healthy subjects and hyperinsulinemic euglycemic clamp in type 2 diabetic patients. Abdominal fat distribution was evaluated by computed tomography (CT) scanning in diabetic patients. The TNF-α polymorphism was detected in three healthy volunteers and three type 2 diabetic patients, all of them being heterozygotes. There was no significant difference in allele frequencies of the −308 polymorphism between healthy subjects (0.0106) and type 2 diabetic patients (0.0114). HOMA index was no significant difference between healthy subjects with and without polymorphism (1.09±0.03 vs. 1.02±0.05). Glucose infusion rate (GIR), an index of insulin sensitivity, was not significantly different between diabetic patients with and without TNF-α polymorphism (40.4±4.1 vs. 45.0±1.8 μmol/kg per min). Moreover, no remarkable effect of TNF-α polymorphism on abdominal fat distribution was observed in diabetic patients. These results suggest that A/G heterozygotes of the TNF-α gene promoter at position −308 play no major role in the pathogenesis of insulin resistance or abdominal fat distribution in Japanese type 2 diabetic patients.

Keywords:  Type 2 diabetes, TNF-α polymorphism, Insulin resistance, Abdominal fat distribution, Japanese