Genetic polymorphisms of Endoplasmic reticulum amino peptidase 1 (ERAP1) and Interferon lambda 4 (IFN-λ4) in Egyptian patients with type 1 diabetes mellitus

The Egyptian Journal of Immunology
Volume 30 (1), January, 2023
Pages: 116–124.
www.Ejimmunology.org
https://doi.org/10.55133/eji.300112
Salma Abo EL Nazar1, Amany A. Ghazy2, Ibrahim Amer3, Salwa Tawfik4, Marwa Nassar5 and Eman M. Osman1
1Department of Immunology & Allergy, Medical Research Institute, Alexandria University, Alexandria, Egypt.

2Department of Microbiology & Immunology, Faculty of Medicine, Kafresheikh University, Kafresheikh, Egypt.

3Department of Hepatology, Gastroenterology & Infectious Diseases, Faculty of Medicine, Kafresheikh University, Kafresheikh, Egypt.

4Department of Internal Medicine, National Research Center, Cairo, Egypt

5Research & Development laboratory at Nefertary Factory.

Corresponding author: Eman M. Osman, Department of Immunology & Allergy, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Email: eman.immunology@gmail.com.

Abstract

Different genetic and environmental factors are implicated in type I diabetes (T1DM) pathogenesis. About 50% of the genetic susceptibility for T1DM is related to human leukocyte antigen (HLA) genes. Other non-HLA genes have variable roles in the destruction of pancreatic β cells. A highly variable gene called endoplasmic reticulum associated with antigen processing gene 1(ERAP1) shares in activating autoreactive CD8+ T lymphocytes, peptide trimming, and subsequent pancreatic β cells destruction. Local production of inflammatory cytokines within the cells of islets of Langerhans is linked to T1DM progression. Different viral and autoimmune disorders have been linked to genetic variations in type III interferon (IFNλs). This study aimed to determine genetic polymorphisms of interferon lambda 4 (IFNλ4rs 73555604) and endoplasmic reticulum aminopeptidases 1 (ERAP1 rs26618) in Egyptian patients with T1DM. The study recruited 120 patients with T1DM from Kafrelsheikh University Hospital and 100 normal controls who were age and sex matched with the patients’ group. Single-nucleotide polymorphism (SNP) genotyping of ERAP1(rs26618) and IFN-λ-4(rs73555604) was performed using real-time polymerase chain reaction. Patients with CC genotype were less likely to develop T1DM than those with TC and TT genotypes for both genes. In addition, T allele frequency in comparison to C allele frequency was significantly increased in T1DM patients when compared to control group (p<0.001). There were positive correlations between studied SNPs for both genes, fasting and postprandial blood glucose levels which suggest the association of these genes with T1DM occurrence. We concluded that the studied SNPs of ERAP1gene (rs26618) and IFNλ-4 gene(rs73555604) may be associated with T1DM development. In addition, T alleles for both genes could be considered risk alleles while C alleles would be regarded as a protective allele. Patients with TC and TT genotypes would be at a higher risk for T1DM than those carrying CC genotype.

Keywords: Type 1 diabetes (T1DM), IFN-λ4 gene, ERAP1 gene, polymorphisms.

Date received: 20 October 2022; accepted: 15 December 2022

PMID: 36592387

 

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