The TNF alpha/G-308A polymorphism influences insulin sensitivity in offspring of patients with coronary heart disease: the European Atherosclerosis Research Study II

Atherosclerosis. 2002 Apr;161(2):317-25. doi: 10.1016/s0021-9150(01)00648-7.


There is accumulating evidence for a role of tumor necrosis factor-alpha (TNF-alpha) in insulin resistance induced by obesity. The purpose of this study was to investigate whether the TNF alpha/G-308A polymorphism was associated with responses to oral glucose and fat tolerance tests in a case--control study comparing male offspring with a paternal history of premature myocardial infarction (cases, n=335) to age-matched controls (n=340) recruited from 14 European university populations. Genotype frequencies did not significantly differ between cases and controls. Among cases, those carrying the A allele exhibited a higher area under the curve for insulin (64.5 vs 55.9 mU h/l, P=0.009), a higher increment between baseline concentration and peak of insulin (63.1 vs 52.8 mU/l, P=0.005) and a greater decrease between peak and insulin at 120 min (49.1 vs 36.8 mU/l, P=0.003) than those with the GG genotype. No such effect was observed in control subjects. No association was observed with response to a fat tolerance test either in cases or in controls. The present results suggest that the TNF alpha/G-308A polymorphism might interact with other susceptibility factors to coronary heart disease to predispose to insulin resistance, and that the ability of TNF-alpha to induce insulin resistance may extend beyond obesity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Analysis of Variance
  • Body Mass Index
  • Case-Control Studies
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / genetics*
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genotype
  • Glucose Tolerance Test
  • Humans
  • Insulin Resistance / genetics*
  • Logistic Models
  • Male
  • Obesity / blood
  • Obesity / genetics
  • Pedigree
  • Polymorphism, Genetic*
  • Reference Values
  • Sampling Studies
  • Sensitivity and Specificity
  • Tumor Necrosis Factor-alpha / genetics*


  • Genetic Markers
  • Tumor Necrosis Factor-alpha