Association of G-2548A Polymorphism in the Promoter of Leptin Gene with Plasma Leptin Level and Risk of Type 2 Diabetes

Leptin, the obese (ob) gene product, is a cytokine-like hormone secreted mainly from adipose tissue; acting on a receptor site in the hypothalamus to inhibit food intake and stimulate energy expenditure. A G-2548G polymorphism in the leptin gene promoter has a strong influence on leptin gene expression and adipose tissue secretion. The aim of this study was to examine the association of the leptin G-2548A promoter polymorphism with leptin plasma level and susceptibility to type 2 diabetes. 100 patients with type 2 diabetes mellitus and 100 healthy controls were screened for the presence of G-2548A polymorphism using PCR-RFLP analysis. Body mass index, fasting leptin and fasting glucose were also determined. Carriers with the GG genotype (20.02±5.6μg/L) had significantly (P<0.001) higher leptin levels than those with the AG genotypes (16.2±5.4μg/L) and AA genotypes (13.42±6.3). Also, LEP -2548GG genotype presented an increased risk of type 2 diabetes (OR: 3.26, 95%CI: 1.5-7.2, P=0.004). In the other words, GG genotypes in the region of -2548 are associated with increased risk of type 2 diabetes. The present study showed that G-2548A LEP polymorphism is important in regulating leptin plasma level and is associated with risk of type 2 diabetes. Thus, this polymorphism may act as a molecular marker for type 2 diabetes.