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

Research output: Contribution to journalJournal article

  • R L Nolsøe
  • Y H Hamid
  • F Pociot
  • S Paulsen
  • K M Andersen
  • K Borch-Johnsen
  • Drivsholm, Thomas
  • T Hansen
  • O Pedersen
  • T Mandrup-Poulsen
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.
Original languageEnglish
JournalGenes and Immunity
Issue number4
Pages (from-to)316-21
Number of pages6
Publication statusPublished - 1 Jun 2006

    Research areas

  • 3' Untranslated Regions, Adult, Aged, Antigens, CD95, Apoptosis, Denmark, Diabetes Mellitus, Type 2, Fas Ligand Protein, Female, Humans, Insulin Resistance, Insulin-Secreting Cells, Male, Membrane Glycoproteins, Microsatellite Repeats, Middle Aged, Polymorphism, Genetic, Promoter Regions, Genetic, Quantitative Trait, Heritable, Receptors, Tumor Necrosis Factor, Tumor Necrosis Factors

ID: 33030373