Association of a microsatellite in FASL to type II diabetes and of the FAS-670G>A genotype to insulin resistance
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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.
|Journal||Genes and Immunity|
|Number of pages||6|
|Publication status||Published - 1 Jun 2006|
- 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