Abstract.
Aims/hypothesis:
Type I (insulin-dependent) diabetes mellitus is the result of a T-cell regulated selective destruction of pancreatic beta cells. There is evidence that the apoptosis inducing T-cell effector, Fas ligand (FasL) could be involved in the pathogenesis of Type I diabetes, probably because FasL-mediated apoptosis is important in maintaining peripheral self-tolerance and in down-regulating an immune response. We therefore evaluated the human FasL gene FASL on chromosome 1q23 as a candidate susceptibility gene for Type I diabetes.
Methods:
The entire FASL (promoter, exons 1–4 and 3'UTR) was scanned for polymorphisms using single strand conformational polymorphism-heteroduplex analysis and direct sequencing.
Results:
We identified two novel polymorphisms, a g-C843T and a g-A475T, in a negative regulatory region of the promoter. A Danish Type I diabetes family collection of 1143 subjects comprising 257 families (420 affected and 252 unaffected offspring) was typed for the g-C843T polymorphism and for a FASL microsatellite. Haplotypes were established and data were analysed using the extended transmission disequilibrium test.
Conclusion/interpretation:
We found no overall evidence for linkage in the presence of association of the FASL polymorphism to Type I diabetes and conclude that FASL does not contribute to the genetic susceptibility to Type I diabetes. [Diabetologia (2002) 45: 134–139]
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Received: 4 July 2001 and in revised form: 12 September 2001
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Nolsøe, R., Kristiansen, O., Larsen, Z. et al. Complete mutation scan of the human Fas ligand gene: Linkage studies in Type I diabetes mellitus families. Diabetologia 45, 134–139 (2002). https://doi.org/10.1007/s125-002-8254-7
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DOI: https://doi.org/10.1007/s125-002-8254-7