The Association of LEP G2548A Polymorphism with Type 2 Diabetes Mellitus in the Iraqi Population

Background: Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder influenced by both environmental and genetic factors. Leptin, a key hormone regulating energy homeostasis and insulin sensitivity, has been linked to T2DM pathogenesis. The LEP gene promoter polymorphism G2548A (rs7799039) has been associated with altered leptin expression and metabolic dysregulation in various populations. Objective: This study investigated the association between the LEP G2548A variant and T2DM risk among Iraqi adults. Materials and Methods: A case-control study was conducted involving 150 T2DM patients and 150 healthy controls matched for age, sex, and BMI. Genotyping of the G2548A polymorphism was performed using allele-specific PCR. Fasting blood glucose, insulin, leptin levels, and lipid profiles were measured. Insulin resistance was assessed using the HOMA-IR index. Associations between genotypes, allelic frequencies, and biochemical parameters were evaluated under multiple genetic models. Results: The frequency of the A allele and AA genotype was significantly higher in T2DM patients compared to controls (41.7% vs. 19.0%, p< 0.00001; OR = 3.39). The AA genotype was associated with a 5.1-fold increased risk of T2DM, while the GA genotype conferred a 2.6-fold risk. Carriers of the A allele showed significantly elevated levels of serum leptin, insulin, and HOMA-IR. These findings suggest a strong association between the LEP G2548A polymorphism and both hyperleptinemia and insulin resistance in T2DM patients. Conclusion: The LEP G2548A polymorphism is significantly associated with increased risk of T2DM and contributes to elevated leptin levels and insulin resistance in the Iraqi population. The A allele may serve as a potential genetic marker for early identification of individuals at higher risk for T2DM.