We investigated the relationship of the A/G variant of the tumor necrosis factor-alpha (TNF-alpha) gene promoter at position -308 with insulin resistance and abdominal fat distribution in type 2 diabetic patients in the Japanese population. The TNF-alpha 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-alpha 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 VSports手机版. 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-alpha polymorphism (40. 4 +/- 4. 1 vs. 45. 0 +/- 1. 8 micromol/kg per min). Moreover, no remarkable effect of TNF-alpha polymorphism on abdominal fat distribution was observed in diabetic patients. These results suggest that A/G heterozygotes of the TNF-alpha 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. .