Type 1 diabetes mellitus (T1DM) is a typical autoimmune disease and results from the destruction of insulin-producing 0 cells of the pancreas. It develops in the presence of genetic susceptibility, even though more than 85% of patients with T1DM do not have a close relative with the disorder. The etiology of T1DM is complex, and both genetic and environmental factors play important roles. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association identified is that with HLA class 11 genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) and DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of the subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. Major histocompatibility complex (MHC) class I chain-related A (MICA) is located in a candidate susceptibility region and activates natural killer (NK) cells, T cells and gamma delta CD8 T cells by its receptor NKG2D. The polymorphism of the MICA gene is associated with T1DM in different populations as demonstrated in several papers published in the last 7 years.
MICA gene polymorphism in the pathogenesis of type 1 diabetes
BROZZETTI, Annalisa;FALORNI, Alberto
2007
Abstract
Type 1 diabetes mellitus (T1DM) is a typical autoimmune disease and results from the destruction of insulin-producing 0 cells of the pancreas. It develops in the presence of genetic susceptibility, even though more than 85% of patients with T1DM do not have a close relative with the disorder. The etiology of T1DM is complex, and both genetic and environmental factors play important roles. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association identified is that with HLA class 11 genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) and DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of the subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. Major histocompatibility complex (MHC) class I chain-related A (MICA) is located in a candidate susceptibility region and activates natural killer (NK) cells, T cells and gamma delta CD8 T cells by its receptor NKG2D. The polymorphism of the MICA gene is associated with T1DM in different populations as demonstrated in several papers published in the last 7 years.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
