Extreme genetic risk for type 1A diabetes in the post-genome era

Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, CO 80045-6511, USA.
Journal of Autoimmunity (Impact Factor: 7.02). 09/2008; 31(1):1-6. DOI: 10.1016/j.jaut.2008.03.003
Source: PubMed

ABSTRACT A series of genes and loci influencing the genetic risk of type 1A (immune-mediated) diabetes are now well characterized. These include genes of the major histocompatibility complex (MHC), polymorphisms 5' of the insulin gene, and PTPN22, as well as more recently defined loci from genome-wide association studies. By far the major determinants of risk for type 1A diabetes are genes within or linked to the MHC and in particular alleles of class II genes (HLA-DR, DQ, and DP). There is evidence that MHC class I alleles contribute and there are additional MHC-linked influences such that for a major subset of relatives of patients there is a risk as high as 80% for siblings, and for the general population a risk as high as 20% can be defined at birth just by analyzing the MHC. We believe the search for additional MHC loci will require analysis of the remarkable long-range identity (up to 9 million base pairs) of extended MHC haplotypes. Current prediction algorithms will likely be greatly improved for the general population when the additional contributing loci of the MHC are defined.

  • Diabetes Technology &amp Therapeutics 06/2013; 15(S2):S2-8-S2-12. DOI:10.1089/dia.2013.0114 · 2.29 Impact Factor
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    ABSTRACT: Type 1 diabetes mellitus (T1D) is a T cell-mediated autoimmune disease that cause destruction of pancreatic islet �- cells. Susceptibility to T1D is determined by interaction between several genetic loci and environmental factors. Alleles at the human leukocyte antigen (HLA) locus explain up to 50% of the familial clustering of T1D, but other loci are also contributed to T1D and there is a universal trial to understand their role in this complex disease. In addition, there is a consensus among epidemiologists that the worldwide incidence rate of type 1 diabetes has been rising in recent decades. The cause of this rise is unknown, but epidemiological studies suggest the involvement of environmental factors, and viral infections in particular. Finding new loci and the pathways in which the destruction of �-cells happen, can lead to possible diagnostic and therapeutic applications of these genetic findings. Also, determining the environmental factors causing T1D is useful, because we can eliminate them and trying to prevent the disease in susceptible individuals by this knowledge.
  • Diabetes Technology &amp Therapeutics 06/2013; 15(S2):S2-29-S2-36. DOI:10.1089/dia.2013.0141 · 2.29 Impact Factor

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Sep 17, 2014

Erin E Baschal