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MICA Gene Polymorphism in the Pathogenesis of Type 1 Diabetes
Author(s) -
GAMBELUNGHE G.,
BROZZETTI A.,
GHADERI M.,
CANDELORO P.,
TORTOIOLI C.,
FALORNI A.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1423.011
Subject(s) - type 1 diabetes , nkg2d , major histocompatibility complex , biology , haplotype , genetics , genetic predisposition , human leukocyte antigen , immunology , genotype , gene , cytotoxic t cell , diabetes mellitus , antigen , endocrinology , in vitro
: Type 1 diabetes mellitus (T1DM) is a typical autoimmune disease and results from the destruction of insulin‐producing β 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 idengified is that with HLA class II 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 γδ 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.