G(–2548)A leptin gene polymorphism in obese subjects is associated with serum leptin concentration and bone mass

INTRODUCTION: Clinical studies have shown either positive or in some other cases negative correlations between leptinemia and bone mineral density (BMD) or bone mineral content (BMC). OBJECTIVES: The aim of the present study was to assess whether these discrepancies might be associated with the effect of G(–2548)A leptin or A326G and A668G leptin receptor gene polymorphisms on serum leptin concentrations or BMD and BMC. PATIENTS AND METHODS: The study included 72 obese patients (39 women and 33 men, aged 46 ±8.8 years; body mass index [BMI] >30 kg/m2). In all subjects, serum creatinine, glucose, lipids, leptin, and insulin were determined. Total fat mass (TFM), BMC, and BMD were assessed using dual energy X ray absorptiometry (Lunar DPX-L). RESULTS: No significant correlations were observed between body mass composition parameters (TFM, lean mass, BMC) or BMD in relation to genotypes. A positive correlation was found between serum leptin concentration and BMI. An inverse association was observed between leptin concentrations and BMC. Multiple regression analysis showed independent correlations of leptinemia with sex (P <0.001), TFM (P <0.000 001), BMC (P = 0.0001), and the presence of (–2548)A allele of the leptin gene (P <0.05). These parameters together accounted for 83% of variability in serum leptin concentrations. CONCLUSIONS: In obese patients, serum leptin concentration shows an independent inverse correlation with BMD and male sex, but positively with TFM and the presence of –2548A allele of leptin gene. These parameters are responsible for 83% of leptin concentration variability. No correlations between the examined polymorphisms and BMC or BMD were found.