Association of a microsatellite in FASL to type II diabetes and of the FAS-670G>A genotype to insulin resistance

Genes Immun. 2006 Jun;7(4):316-21. doi: 10.1038/sj.gene.6364300. Epub 2006 May 4.


Type II diabetes is caused by a failure of the pancreatic beta-cells to compensate for insulin resistance leading to hyperglycaemia. There is evidence for an essential role of an increased beta-cell apoptosis in type II diabetes. High glucose concentrations induce IL-1beta production in human beta-cells, Fas expression and concomitant apoptosis owing to a constitutive expression of FasL. FASL and FAS map to loci linked to type II diabetes and estimates of insulin resistance, respectively. We have tested two functional promoter polymorphisms, FAS-670 G>A and FASL-844C>T as well as a microsatellite in the 3' UTR of FASL for association to type II diabetes in 549 type II diabetic patients and 525 normal-glucose-tolerant (NGT) control subjects. Furthermore, we have tested these polymorphisms for association to estimates of beta-cell function and insulin resistance in NGT subjects. We found significant association to type II diabetes for the allele distribution of the FASL microsatellite (P-value 0.02, Bonferroni corrected). The FAS-670G>A was associated with homeostasis model assessment insulin resistance index and body mass index (P-values 0.02 and 0.02). We conclude that polymorphisms of FASL and FAS associate with type II diabetes and estimates of insulin resistance in Danish white subjects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Aged
  • Apoptosis
  • Denmark
  • Diabetes Mellitus, Type 2 / genetics*
  • Fas Ligand Protein
  • Female
  • Humans
  • Insulin Resistance / genetics*
  • Insulin-Secreting Cells / cytology
  • Male
  • Membrane Glycoproteins / genetics*
  • Microsatellite Repeats*
  • Middle Aged
  • Polymorphism, Genetic
  • Promoter Regions, Genetic / genetics
  • Quantitative Trait, Heritable
  • Receptors, Tumor Necrosis Factor / genetics*
  • Tumor Necrosis Factors / genetics*
  • fas Receptor


  • 3' Untranslated Regions
  • FAS protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factors
  • fas Receptor