Preliminary insight into the potential role of Leptin Receptor Polymorphisms in Type 2 Diabetes Risk: case-control...

Area of Science:

• Genetics
• Endocrinology
• Metabolic Disorders

Background:

• Type 2 diabetes mellitus (T2DM) is strongly associated with obesity.
• Leptin (LEP) is a key adipokine regulating metabolic processes and energy balance.
• Genetic variations in the leptin receptor gene (LEPR) may influence T2DM and obesity susceptibility by disrupting LEP signaling.

Purpose of the Study:

• To investigate the association between LEPR gene polymorphisms and the risk of T2DM.
• To analyze the role of specific LEPR variants (rs1137100, rs1137101, rs1805094) in T2DM susceptibility within a Southeastern Iranian population.

Main Methods:

• A case-control study involving 450 T2DM patients and 450 healthy controls.
• Genomic DNA extraction from peripheral blood samples.
• Genotyping of LEPR polymorphisms using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).
• Computational analysis to construct a gene-gene interaction network.

Main Results:

• The rs1137100 (A/G) polymorphism was associated with a reduced risk of T2DM across multiple genetic models.
• Polymorphisms at rs1137101 (G/A) and rs1805094 (G/C) were linked to an increased risk of T2DM.
• Significant linkage disequilibrium (LD) was observed among the studied LEPR variants and haplotypes.
• LEPR was identified as a central hub gene interacting with LEP, PTPN11, STAT3, POMC, JAK2, IL6, and SOCS3.

Conclusions:

• LEPR gene polymorphisms show a significant correlation with T2DM risk.
• These findings highlight the substantial role of genetic factors in the development of T2DM.
• Understanding LEPR variations can improve insights into endocrine dysregulation and inform clinical genetic profiling.