Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 61 4 2023 07 04 238 246 Mahafarin Maralani Department of Medical Oncology, MOCA, University Hospital Antwerp (UZA), Antwerp, Belgium Tufan Cankaya Department of Medical Genetics, Dokuz Eylul University, Izmir, Turkey Esra Ataman Department of Medical Genetics, Dokuz Eylul University, Izmir, Turkey Yavuz Tokgoz Division of Pediatric Gastroenterology and Nutrition, Adnan Menderes University, Aydın, Turkey Erkan Kaytankas Department of Medical Genetics, Dokuz Eylul University, Izmir, Turkey Nur Arslan 1 Department of Medical Oncology, MOCA, University Hospital Antwerp (UZA), Antwerp, Belgium. AND Division of Pediatric Metabolism and Nutrition, Dokuz Eylul University, Izmir, Turkey Behzad Baradaran Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Khalil Hajiasgharzadeh Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Ayfer Ulgenalp Department of Medical Oncology, MOCA, University Hospital Antwerp (UZA), Antwerp, Belgium.AND Department of Medical Genetics, Dokuz Eylul University, Izmir, Turkey. ANDDepartment of Pediatric Genetics, Dokuz Eylul University, Izmir, Turkey 2021 01 28 2023 01 21 Obesity is becoming a concerning disease in developing countries. Like other multifactorial diseases, genetics plays a substantial role in the development of this disease. We tried to investigate genetic variations (mutation/polymorphism) of GLP-1R gene in children diagnosed with obesity and to identify their possible connections with obesity and other conditions. Genomic DNA was extracted from 162 overweight/obese patients and 100 controls. Later, full exon sequencing and association studies were carried out. Three polymorphisms and one mutation were detected in the fourth and fifth exons of the GLP-1R gene. Some variations were detected in three cases from which 1/3 had non-alcoholic fatty liver disease (NAFLD) but none showed insulin resistance (IR). There were also statistically meaningful results for ‘Odds Ratio’ among different genotypes and allele frequencies in groups with NAFLD and/or IR. In addition, there was an increase in risk for NAFLD and a decrease in risk for IR. In the homozygous group, also the prospect of IR was double declined. Patients with the A allele of this polymorphism showed a drop in risk for IR as well. GLP-1R polymorphisms could influence obesity and diabetes and thus the functional analysis of the GLP-1R polymorphisms is benevolent. https://acta.tums.ac.ir/index.php/acta/article/view/9128 https://acta.tums.ac.ir/index.php/acta/article/download/9128/5778