Association of LEPR gene rs1137100 (Lys109Arg) & rs1137101 (Gln223Arg) polymorphisms with Type 2 Diabetes Mellitus in young Bangladeshi population: a pilot study

Abstract

"Background: Youth-onset Type 2 Diabetes Mellitus (T2DM) is an emerging global public health concern. Polymorphisms in the LEPR (leptin receptor) gene, specifically rs1137100 (Lys109Arg) and rs1137101 (Gln223Arg) have been widely linked to an increased risk of T2DM due to their roles in insulin resistance, energy homeostasis, and obesity. However, genetic risk factors for T2DM in young Bangladeshi populations remain unexplored. Objective: In this study, we tried to determine the required sample sizes and provide initial data for investigating the association of LEPR gene polymorphisms (rs1137100 and rs1137101) with youth-onset T2DM in full-scale research. Methods: A case-control pilot study was conducted involving 56 Bangladeshi participants (18 T2DM cases, 38 NGT controls) aged 18- 29 years. Clinical and biochemical data were gathered. Blood samples were collected for DNA extraction and genotyping using PCR-RFLP and sequencing. Statistical analysis was performed using the t-test and chi-square test to show any significant difference between the groups. Results: The T2DM group showed higher waist-hip ratios, triglycerides, and altered glycemic profiles compared to controls. In rs1137100 polymorphism, the AA genotype was more frequent in T2DM, while AG and GG genotypes were predominant in controls. In rs1137101, the AG genotype was more common in T2DM. However, there were no significant associations between LEPR polymorphisms and T2DM risk. To ensure adequate statistical power, 138 participants/group (rs1137100) and 27,450/group (rs1137101) are required for future studies. Conclusion: LEPR polymorphisms showed genotype variations but no significant risk association, demanding large-scale studies."