RAGE gene polymorphism (rs1800625) and type 1 diabetes mellitus: A potential new model for early diagnosis and risk prediction

Amal A. Mohamed; Feras Al-Obeidat; Gamil M.  Abdallah; Ibrahim T. Ibrahim; Nada S.  Ali; Mona A.  Hussein; Wael Hafez; Mina W. Girgiss; Hassan  Shalby; Doaa EL-Bohy; Rasha Elgamal; Maysa I. Farghly; Mahmoud M. Shaheen; Reem Elmahdy; Raghda A. Nagaty; Noheir AIF. Hassan; Amel Hamdi; Mohamed O. Mahmoud

doi:10.52225/narra.v5i1.1603

Authors

Amal A. Mohamed Department of Biochemistry and Molecular Biology, National Hepatology and Tropical Medicine Research Institute, General Organization of Teaching Hospitals and Institutions, Cairo, Egypt https://orcid.org/0000-0002-2014-2239
Feras Al-Obeidat College of Technological Innovation, Zayed University, Abu Dhabi, United Arab Emirates
Gamil M. Abdallah Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
Ibrahim T. Ibrahim Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
Nada S. Ali Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt https://orcid.org/0009-0007-9753-8278
Mona A. Hussein Department of Internal Medicine, National Institute of Diabetes and Endocrinology, General Organization of Teaching Hospitals and Institutions, Cairo, Egypt
Wael Hafez Medical Research and Clinical Studies Institute, The National Research Centre, Cairo, Egypt https://orcid.org/0000-0003-1203-0808
Mina W. Girgiss Medical Research and Clinical Studies Institute, The National Research Centre, Cairo, Egypt https://orcid.org/0000-0003-0857-399X
Hassan Shalby Department of Internal Medicine, Faculty of Medicine, Misr University for Science and Technology, Cairo, Egypt
Doaa EL-Bohy Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt https://orcid.org/0000-0002-4283-9651
Rasha Elgamal Department of Clinical Pathology, Faculty of Medicine, Suez University, Suez, Egypt
Maysa I. Farghly Department of Clinical Pathology, Faculty of Medicine, Suez University, Suez, Egypt https://orcid.org/0009-0006-3226-9372
Mahmoud M. Shaheen Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
Reem Elmahdy Department of Internal Medicine, Faculty of Medicine, Suez University, Suez, Egypt https://orcid.org/0009-0006-7120-4467
Raghda A. Nagaty Department of Clinical and Chemical Pathology, Research Institute of Ophthalmology, Giza, Egypt
Noheir AIF. Hassan Faculty of Medicine, Aswan University, Aswan, Egypt https://orcid.org/0000-0001-7865-4213
Amel Hamdi Hematology and Molecular Biology, Health Sciences, College of Health Science, Abu Dhabi University, Abu Dhabi, United Arab Emirates https://orcid.org/0000-0002-6510-8587
Mohamed O. Mahmoud Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt https://orcid.org/0000-0002-6737-8142

DOI:

https://doi.org/10.52225/narra.v5i1.1603

Keywords:

Type 1 diabetes mellitus, autoimmune, receptor for advanced glycation end-products gene, RAGE, polymorphism

Abstract

Studies have associated advanced glycation end-products (AGEs) and the polymorphism of the AGEs receptor (RAGE) gene with clinical disorders, such as diabetes, in certain ethnic groups. However, its association with type 1 diabetes mellitus (T1DM) in Egyptians has not yet been explored. The aim of this study was to investigate the association between the RAGE gene polymorphism rs1800625 and T1DM susceptibility in Egyptians. A case-control study was conducted with 177 T1DM patients and 177 age- and sex-matched healthy controls. Variables included glycemic markers (fasting blood glucose (FBG), postprandial blood glucose (PBG), hemoglobin A1c (HbA1c)), anthropometric measurements (waist circumference, body mass index (BMI)), lipid profile (total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL)), renal function (albumin-to-creatinine ratio (A/C ratio), serum creatinine), and history of hypertension and smoking. Genotype distribution and allele frequency of the RAGE rs1800625 polymorphism (TT, TC, CC genotypes; T and C alleles) were assessed. This study identified the RAGE rs1800625 polymorphism as a significant genetic factor associated with T1DM susceptibility. The CC genotype was significantly more prevalent in patients compared to controls (29.9% vs 11.9%; OR: 3.62; 95%CI: 1.87–6.97; p<0.001). Similarly, the C allele was more common in patients (54.5% vs 41.0%, OR: 1.73; 95%CI: 1.28–2.33; p<0.001). Multivariate analysis revealed that HbA1c (adjusted OR (aOR): 12.97; 95%CI: 4.00–42.05; p<0.001), FBG (aOR: 8.96; 95%CI: 1.59–50.47; p=0.010), and the rs1800625 polymorphism (aOR: 1.82; 95%CI: 1.146–2.876, p=0.010) were significant predictors of T1DM. In conclusion, a genetic association was found between the RAGE gene polymorphism rs1800625 and T1DM susceptibility, with the CC genotype and C allele being more common in T1DM patients. FBG, HbA1c, and rs1800625 were identified as key predictors for T1DM, with HbA1c being the strongest. These findings highlight the importance of integrating genetic and metabolic factors in managing T1DM.