الفهرس 
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Abstract
Diabetes mellitus is a group of metabolic disorders characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.
Several pathogenic processes are involved in the development of diabetes. These include destruction of the beta cells of the pancreas with consequent insulin deficiency and abnormalities that result in resistance to insulin action. Symptoms indicating diabetes mellitus are signs of hyperglycemia, such as thirst, polyuria, glycosuria, weight loss and others such as fatigue, blurred vision and recurrent infections.
Multifactorial inheritance suggests that a disease results from the interaction between environmental and genetic factors. The genetic factors are certain alleles of polymorphic genes involved in T1DM; such alleles are known as predisposing to T1DM.
Genes for Type1DM (T1DM) may provide susceptibility to, or protection from, the disease. Although many chromosomal loci associated with such activities have been located, few true genes have been identified which can divide into 2 major subdivisions:
HLA genes.
Non HLA genes.
HLA are accounting for about 60% genetic susceptibility for the disease. The HLA genes are a cluster of genes on chromosome 6 p 21.The genes encode glycoproteins that are found on the surfaces of most cells and help the immune system to distinguish between self and non-self.
About 20 non-HLA loci contributing to disease susceptibility have been identified include: Insulin gene , cytotoxic T-lymphocyte antigen-4 gene (CTLA-4) ,PTPN22 gene ,and IL2RA gene.
PTPN22 Gene:
(PTPN22) Protein tyrosine phosphatase non-receptor type 22 is a protein encoded by the PTPN22 gene. PTPN22 affects the responsiveness of T and B cell and mutations are associated with increases or decreases in risks of autoimmune diseases.
PTPN22 gene is located on the short arm of chromosome 1 near the centromere (1p13.2) and encodes a lymphoid protein tyrosine phosphatase (LYP), LYP through formation of a complex with C-terminal Src Kinas (CSK) suppresses the downstream mediators of T-cell receptor signaling and down regulates the activation of T cells.
A common mutation in PTPN22 gene is a C to T substitution at position 1858 (C1858T) that results in substitution of amino acid arginine with tryptophan at codon 620 (R620W), which is located in the LYP–Csk interaction motif. This mutation leads to partial or complete disruption of the binding of PTPN22 Csk, Carriers of C1858T show reduced signal transduction through the TCR receptor.
The autoimmune-associated SNP PTPN22 1858C>T encodes an arginine to tryptophan substitution at amino acid 620 (Arg620Trp) in the first proline-rich motif of the PTPN22 protein.
Studies of human and mouse cells show that PTPN22 is a potent inhibitor of T-cell activation by inhibitory dephosphorylation.
A single nucleotide polymorphism (SNP) at position 1858 of PTPN22 was reported to be associated with T1D in many populations.