الفهرس 
Diabetes MellitusOnly 14 pages are availabe for public view
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Abstract
Type 1 diabetes mellitus (DM) is a multisystem disease with both biochemical and anatomic/structural consequences. It is a chronic disease of carbohydrate, fat, and protein metabolism caused by lack of insulin, which results from marked and progressive inability of the pancreas to secrete insulin because of autoimmune destruction of the beta cells.
Type 1 diabetes (T1D) is a complex diseases that is believed to be caused by multiple genetic factors that increase vulnerability to one or more environmental factors. The presence of risk alleles at a given T1D risk locus is only predictive of an increased risk compared to individuals carrying neutral or protective alleles. Although most genetic factors in complex diseases are believed to confer moderate to small individual effects, the sum and possible interaction between these factors may have a large impact on disease status
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 and Non HLA genes
Polymorphisms of the class II human leukocyte antigen (HLA) genes that encode DR and DQ are the major genetic determinants of type 1 DM. Approximately 95% of patients with type 1 DM have either HLA-DR3 or HLA-DR4. Heterozygotes for those haplotypes are at significantly greater risk for DM than homozygotes. HLA-DQs are also considered specific markers of type 1 DM susceptibility. In contrast, some haplotypes (eg, HLA-DR2) confer strong protection against type 1 DM CD226 (also known as DNAM-1) is a 67 kDa type I membrance protein involved in the adhesion and co-stimulation of T cells .it is location on chromosome 18 q22.2 . It belongs to the immunoglobulin supergene family of receptors, containing two Ig-like domains in the extracellular region and is constitutively expressed on the majority of natural killer (NK) cells, CD4+ and CD8+ T cells, platelets, monocytes and a subset of B cells.
A single nucleotide polymorphism (rs763361 C>T) in exon 7 of CD226 gene (located at 18q22.3) has been associated with T1D etiology in recent years. In that polymorphism, the base Cytosine is replaced by Thymine, resulting in replacement of Glycine at residue 307 by serine (Gly307Ser
The aim of this work is to study the association of CD226 polymorphism with T1D etiology in Egyptian children.
Patient and method:-
In this case-control study, 74 children with T1D wrere enrolled from the inpatient ward and the pediatric endocrinology clinic of Menoufia University Hospital from June to October 2017. Any patient from the age of 6 months to 18 years with T1D was eligible for inclusion in the study. Diabetes mellitus was diagnosed according to the guidelines of the American diabetes association. A child was deemed diabetic in the presence of one of the following (1) Fasting plasma glucose was ≥126 mg/dl (2) Presence of symptoms of hyperglycemia or hyperglycemic crisis and random plasma glucose ≥ 200 (3) HbA1C ≥6.5%.
Exclusion criteria included (1) Age under 6 months (when T1D is highly unlikely) or over 18 years old (2) Type 2 diabetes (3) Specific types of diabetes like maturity-onset diabetes of the young (MODY), drug- induced diabetes, and diabetes associated with genetic syndromes such as Down and Turner syndromes.
Besides the patient group, 82 healthy children were recruited as a control group. Children in the control group had no symptoms of diabetes, no family history of T1D or other autoimmune diseases, and normal random plasma glucose levels.
A full history was obtained, including personal and family history of diabetes and other autoimmune diseases. Physical examination, including anthropometric measurements, was performed. Investigations included routine laboratory investigations, glycosylated hemoglobin (HA1c), and lipid profile. Furthermore, genotyping for CD226 was performed for all patients and controls. Patients were also thoroughly evaluated for the presence of diabetic complications like nephropathy, neuropathy, and retinopathy.
CD226 gene rs763361 C<T polymorphism, located in exon 7, was detected by a polymerase chain reaction followed by Restriction fragment length polymorphism (PCR–RFLP) assay. We used three genetic models, namely ”genotype/codominant”, ”dominant”, and ”recessive” models to test the association of rs763361 polymorphism with diabetes risk.