The molecular genetics of type 1 diabetes: new genes and emerging mechanisms.
Susceptibility to type 1 diabetes (T1D) is determined by complex interactions 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, and the remainder is contributed to by multiple loci, of which only four were known until recently. First-stage results of genome-wide association (GWA) studies performed with high-density genotyping arrays have already produced four novel loci and the promise that, with the completion of the second stage of the GWA studies, most of the genetic basis of T1D will be known. We will review what is known to date about the mechanisms of genetic susceptibility to T1D, with special emphasis on possible diagnostic and therapeutic applications of these recent genetic findings.
Ounissi-Benkalha
Houria
H
Endocrine Genetics Laboratory, McGill University Health Center, Montreal Children's Hospital Research Institute, 2300 Tupper, Montréal, Québec H3H 1P3, Canada.
Polychronakos
Constantin
C
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics; D060908:CTLA-4 Antigen; D053487:DEAD-box RNA Helicases / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics; D000072640:Interferon-Induced Helicase, IFIH1; D015810:Linkage Disequilibrium; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006680:HLA Antigens; D007328:Insulin; D015375:Receptors, Interleukin-2; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1