Abstract
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 language | English |
|---|---|
| Journal | Genes and Immunity |
| Volume | 7 |
| Issue number | 4 |
| Pages (from-to) | 316-21 |
| Number of pages | 6 |
| ISSN | 1466-4879 |
| DOIs | |
| Publication status | Published - 1 Jun 2006 |
Keywords
- 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
