الفهرس 
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Abstract
Summary
Diabetes Mellitus represents one of the highest challenges in our century, due to the fact that in the last 20 years the number of patients with DM has doubled, at present affecting hundreds of millions of people worldwide, both in developed countries and in developing ones, as well.
Type 1 diabetes mellitus (T1DM) is a form of diabetes mellitus in which not enough insulin is produced by islet cells in the pancreas and subsequently results in high blood sugar levels. However, the exact cause of T1DM is still unknown. In most cases, it is an autoimmune disease.
The triggering of autoimmunity against beta-cells arises from a multifaceted interaction between multiple genetic and environmental risk factors.
The programmed death- (PD-1) /PD-1 ligand (PD-L1) pathway plays an important role in regulating T cell activation and maintaining peripheral tolerance. Accumulated studies showed that PD-1/PD-L1 pathway was involved in the development of type 1 diabetes (T1DM), as a costimulatory molecule that inhibits T cell proliferation, PD-1 deficiency was shown to increase the risk of T1DM in nonobese diabetic (NOD) mice. Studies had shown that low PD-1 might increase T cell proliferation and activation which lead to the destruction of beta cells, providing a possible mechanism for T1DM.
The present work is a case control study that included 80 type1 diabetic children and adolescents and 76 unrelated healthy controls. The patients were recruited from Pediatric Endocrinology Clinic, Beni-Suef University. They were 28 males (35.0%) and 52 females (65.0%), with a mean age of 10.0 ± 3.2 SD.
The aim of the study is to investigate the association of genetic polymorphisms in PD-1 and PD-L1 with T1DM susceptibility in Egyptian population.
All children and adolescents included in the study were subjected to a detailed history, complete general examination, and laboratory tests (HbA1c, serum high density lipoprotein, serum low density lipoprotein, serum triglycerides, TSH, freeT4).and PD-1 SNP (rs34819629), PD-L1 SNPs (rs2297137 and rs4143815) were don by allelic discrimination technique using real time PCR .
The study showed that PD-L1 SNP rs2297137 was significantly associated with T1DM while PD-L1 SNP rs4143815 was insignificantly associated with T1DM. People carrying the C allele and A allele of rs4143815 and rs2297137 respectively suffering less risk of T1DM and no association was found in PD-1 SNP (rs34819629) with T1DM.
As regard haplotyping results, it was found the presence of a level of linkage disequilibrium between PD-L1 (rs2297137 and rs4143815) SNPs in Egyptian populations.
The study showed a higher incidence of T1DM in females than males.
In conclusion: our results indicated that PD-L1 SNP rs2297137 was significantly associated with T1DM while PD-L1 SNP rs4143815 was insignificantly associated with T1DM and no association was found between PD-1 SNP (rs34819629) and T1DM.