The tumour necrosis factor alpha -238 G --> A and -308 G --> A promoter polymorphisms are not associated with insulin sensitivity and insulin secretion in young healthy relatives of Type II diabetic patients

Diabetologia. 2000 Feb;43(2):181-4. doi: 10.1007/s001250050027.


Aims/hypothesis: Tumour necrosis factor-alpha (TNF-alpha) is believed to influence skeletal muscle insulin resistance. Two G --> A transitions in the promoter region of TNF-alpha at position -238 and -308 have been identified that could play a part in transcriptional regulation of the gene. Insulin resistance is an independent familial trait that predicts the development of Type II (non-insulin-dependent) diabetes mellitus. We investigated the influence on insulin sensitivity and insulin secretion of both polymorphisms in a cohort of young healthy relatives of patients with Type II diabetes.

Methods: We examined 109 first-degree relatives of Caucasian patients with a history of Type II diabetes, who underwent extensive metabolical and anthropometrical phenotyping, and determined the TNF-alpha -238 and -308 G --> A promoter polymorphisms.

Results: For the -238 polymorphism, 3 probands (76.1%) were homozygous for the G-allele, 25 probands (22.9%) were heterozygous and 1 proband (0.9%) was homozygous for the A-allele. For the -308 polymorphism, 83 probands (76.1%) were homozygous for the G-allele, 24 probands (22.0%) were heterozygous and 2 probands (1.18%) were homozygous for the A-allele. Probands with and without the polymorphism did not differ in insulin sensitivity (p = 0.78), insulin-concentrations and C-peptide concentrations in oral glucose tolerance tests (p > 0.05).

Conclusions/interpretation: We could not detect an association between insulin sensitivity or insulin secretion and TNF-alpha promoter polymorphisms in our cohort. The polymorphisms occur at the same frequencies in probands with either low or high insulin sensitivity.

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genotype
  • Glucose Clamp Technique
  • Heterozygote
  • Homozygote
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Male
  • Middle Aged
  • Point Mutation
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Tumor Necrosis Factor-alpha / chemistry
  • Tumor Necrosis Factor-alpha / genetics*


  • Blood Glucose
  • Insulin
  • Tumor Necrosis Factor-alpha