Leptin promoter G2548A variant, elevated plasma leptin levels, and increased risk of Type 2 diabetes with CAD in Iranian patients: A genetic association study

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a significant risk factor for coronary artery disease (CAD). Leptin polymorphism is known to be associated with obesity and Type 2 diabetes mellitus. This study aimed to investigate the possible links between a specific leptin polymorphism (LEP 2548G/A) and plasma leptin level with the risk of Type 2 diabetes mellitus patients with CAD in the Iranian population for the first time. METHODS AND RESULTS: A total of 150 patients with Type 2 diabetes mellitus and CAD were included in the study, along with 150 nondiabetic controls. Blood samples were collected from participants. Biochemical analysis and genotyping were done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The plasma leptin level was higher in females in the case group. There was a positive correlation between females and obese diabetic subjects (P < 0.001). Regarding the single-nucleotide polymorphism in the leptin gene promoter, we found that the variant genotypes AA and GG were associated with a twofold (OR = 2.09, P = 0.006) and fourfold (OR = 4.2, P = 0.017) increased risk of Type 2 diabetes mellitus patients with CAD, respectively. The GG genotype was also associated with obesity and higher plasma leptin level in the case group (OR = 4.92, P < 0.001). CONCLUSIONS: Leptin G2548A and plasma leptin levels may contribute to Type 2 diabetes with CAD in the Iranian population.