title: Relationship of the tumor necrosis factor-alpha -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-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 (0.0106) 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.
authors.affiliation: Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Furuta
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yano
authors.forename: Kuninobu
authors.initials: K
authors.lastname: Ito
authors.forename: E C
authors.initials: EC
authors.lastname: Gabazza
authors.forename: Akira
authors.initials: A
authors.lastname: Katsuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kouhei
authors.initials: K
authors.lastname: Ohtake
authors.forename: Naoki
authors.initials: N
authors.lastname: Hirata
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hori
authors.forename: Rika
authors.initials: R
authors.lastname: Araki-Sasaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sumida
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Adachi
mesh_terms: D000005:Abdomen; D000225:Adenine; D000273:Adipose Tissue / Q000033:anatomy & histology*; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006147:Guanine; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D000225:Adenine