الفهرس 
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Abstract
Type 1 diabetes (T1D) is an autoimmune condition in which the body cannot produce enough insulin. T1D is caused by both humoral and cell-mediated immune response, which includes natural killer cells, myeloid cells, and lymphoid cells such as CD4 T cells, CD8 T cells, and B cells. Insulitis, which is described as an inflammatory lesion of the islet followed by the loss of pancreatic cells, is the pathophysiological hallmark of T1D.
Genetic factors are considered a major component contributing to T1D pathogenesis. Currently, >60 susceptible loci of T1D have been identified by genetic studies. The HLA region is responsible for 40% to 50% of the genetic risk. Moreover, multiple genetic variants have also been reported to be associated with T1D, including, CTLA4, PTPN22, IL2RA, IFIH1and IL7R.
Epigenetic factors serve as a bridge to link risk genes and environmental insults, so they regulate the expression of T1D susceptible genes involved in antigen presentation
ERAP1 belongs to the M1 family of aminopeptidases, and it’s in charge of trimming peptides that are longer than eight or nine amino acids so that they can be loaded onto MHC-I proteins and presented to particular CD8 T lymphocytes. It is polymorphic, and various single nucleotide polymorphisms (SNPs) in its gene have been linked to illness susceptibility, including viral infections and autoimmune diseases.
Interferons (IFNs) are characterized by their ability to induce antiviral activity in target cells; blood and tissue concentrations of type III interferons increase in a different of autoimmune disease.
IFNL4 has antiviral activity against HCV, Coxackivirus; which are considered as one of environmental factors that triggers T1D.
The present study aimed to detect IFNL4 (rs 73555604) and ERAP1 polymorphism (rs26618) in patients with type I diabetes mellitus. It was conducted on 40 patients with type I diabetes mellitus recruited from Faculty of Medicine, Kafr Elsheikh University and 20 healthy volunteers’ age and sex matched.
Detection of IFNL4 (rs 73555604) and ERAP1 (rs26618) polymorphism was done by DNA extraction technique using (QIA amp DNA Blood Mini Kit), genotyping.
Our results revealed that allelic distribution of ERAP1 (rs26618) in T1D patients and control group was statistically significant different. There was a significant increase in T allele frequency in comparison to C allele frequency (P =0.030, OR=2.414 95% CI: 1.09-
Also there was a statistically significant different in TC and TT genotypes between T1D patients and control group as P = 0.002 and 0.037 respectively
Also allelic distribution of IFNL4 (rs 73555604) in T1D patients and control group was statistically significant different, there was a significant increase in T allele frequency in comparison to C allele frequency with (P=0.048, OR=2.18, 95% CI: 1.01- 4.72)
Also there was a significant statistical different in TC and TT genotype expression between T1D patients and control group (P =0.007and 0.016 respectively).
6.2. Conclusion:
from our results we can conclude that genetic variants of ERAP1 (rs26618) and IFNL4 rs 73555604 are associated with the T1D development in Egyptian patients.
Moreover high diabetic profile indices were associated with TT genotype when compared to other genotypes.
6.3. Recommendations
● Detecting other polymorphisms of both ERAP and IFNL in T1D patients.
● Studying the effect of these polymorphism on larger number of patients
● Studying gene expression of ERAP and IFNL polymorphism in immune cells rather than using peripheral blood
● Studying the effect of gene silencing of IFNL4 and ERAP1 on T1D pathogenesis
● Studying the prognostic value of genetic variants of ERAP1 and IFNL4