Molecular Genetics and Epidemiology of Japanese Type 1 Diabetes

Author(s): Eiji Kawasaki , Katsumi Eguchi .

Journal Name: Current Pharmacogenomics

Volume 3 , Issue 3 , 2005

Abstract:

Type 1 diabetes is an organ-specific autoimmune disease characterized by T-cell mediated destruction of pancreatic β-cells. A variety of environmental and genetic factors are involved in the development of the disease. The human leukocyte antigen (HLA) class II genes (termed IDDM1) are the major genes associated with susceptibility to type 1 diabetes. The highest risk for type 1 diabetes in Caucasian population is associated with individuals expressing both DRB1*0301-DQB1*0201 and DRB1*0401-DQB1*0302. However, HLA-DRB1*0405-DQB1*0401, HLADRB1* 0901-DQB1*0303 and HLA-DRB1*0802-DQB1*0302 are three major susceptible haplotypes in Japanese patients with type 1 diabetes. In contrast, the most protective HLA DR-DQ haplotype, DRB1*1501-DQB1*0602, is universal. Other genetic factors reported in type 1 diabetes include the polymorphisms in insulin gene (IDDM2), CTLA4 gene (IDDM12), PTPN22 gene, IL-18 gene, TNF-α gene, Neuro D/BETA 2 gene, Vitamin D receptor gene, and SDF-1 gene. Within the last decade, a number of immunological and environmental manipulations in animal models of type 1 diabetes, NOD mouse and BB rat, have been reported. In humans, two major trials have been conducted to try to prevent type 1 diabetes with administration of insulin and nicotinamide (DPT-1 and ENDIT). To date, no treatment has been shown to prevent human type 1 diabetes. However, if a safe and effective therapy is identified, one should consider the use of agent for high risk individuals to prevent diabetes, as well as for the patients with type 1 diabetes in adults who are often diagnosed as having type 2 diabetes to preserve residual β-cell function based on the findings of both immunogenetic and pharmacogenetic testing to predict responders from non-responders.

Keywords: type diabetes, autoantibodies, genetics, heterogeneity, immunology, autoantigen

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Article Details

VOLUME: 3
ISSUE: 3
Year: 2005
Page: [191 - 199]
Pages: 9
DOI: 10.2174/1570160054864030
Price: $58

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