Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by selective destruction of pancreatic β-cells resulting in insulin deficiency. The genetic determinants of T1D susceptibility have been linked to several loci, in particular to the human leukocyte antigen (HLA) region, which accounts for 50% of the genetic risk of developing T1D. Multiple genes in the HLA region, which are in strong linkage disequilibrium, are thought to be involved. Another important locus, with a smaller effect on genetic predisposition to T1D, is the insulin gene. The advent of numerous single nucleotide polymorphism markers and genome screening has enabled the identification of dozens of new T1D susceptibility loci. Some of them appear to predispose to T1D independently of the HLA and may be important in families with T1D who lack strong HLA susceptibility. Other loci may interact with each other to cause susceptibility. The autoimmune response against β-cells can also be triggered by environmental factors in the presence of a predisposing genetic background. Deciphering the environmental and genetic factors involved should help to understand the origin of T1D and aid in the design of individualized prevention programs.
Abstract
Introduction
Inheritance of Immunologic Markers and Development of Diabetes
Major Histocompatibility Complex
HLA Molecules in a Trimolecular Complex Determine T1D Susceptibility
MHC Class I Chain-related Gene A
The Variable Number of Tandem Repeats (VNTR) Locus of the Insulin Gene
The Cytotoxic T Lymphocyte Associated Antigen 4 Gene
The Protein Tyrosine Phosphatase N22 Gene
Other Candidate Markers and Lessons from the Recent Genome-wide Association Studies
Genetic susceptibility to T1D in Koreans
Clinical Heterogeneity of Diabetes in Young Asian Patients
Conclusion
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