Effects of leptin and leptin receptor polymorphisms on metabolic parameters in Type 2 diabetic patients
Leptin is an important regulator of the adipose tissue mass and bone formation. Single-nucleotide polymorphisms (SNPs) rs7799039 and rs1137101 in leptin (LEP) and leptin receptor (LEPR) genes, respectively, are associated with cardiovascular disease, inflammation and osteoarthritis. The aim of this study was to investigate the association  of leptin-related SNPs with the metabolic disturbances in Type 2 diabetic (T2D) patients. Methods. A total of 61 T2D patients (M/F: 34/27, age 55.1±1.2, T2D duration 6.29±0.67 yrs, BMI 32.5±0.9 kg/m2, HbA1c 7.92±0.19 %) were included. In all the LEP SNP 2548G>A and LEPR SNP 223Q>R were determined by PCR-RFLP. Serum lipid metabolism parameters were measured spectrophotometrically. There were estimated plasma total and high molecular weight adiponectin, insulin, leptin, osteoprotegerin (OPG), retinol-binding protein-4 (RBP4), lipocalin-2, matrix metalloproteinase-9 (MMP-9) levels etc. by ELISA. Insulin resistance (IR) was assessed using homeostasis model assessment (HOMA-IR) algorithm and as adipose IR (Adipo-IR, NEFAxinsulin). Unpaired Student’s t test, Fisher's test and χ2 test were used. Data are expressed as mean±SEM or median (25th-75th percentile). Results. Comparing with control subjects (n=21) T2D patients were characterized by significant (p<0.05-0.0001) IR, hypoadiponectinemia, increase in plasma NEFA, triglycerides, OPG, RBP4, and fetuin A levels. Homozygous genotypes GG vs AA for rs7799039 and QQ vs RR for rs1137101 were compared in T2D subjects. There was no difference in BMI and leptin levels among both SNPs. On the other hand, LEP SNP (GG vs AA) was associated with the levels of Adipo-IR (104.8 mmol/L x pmol/L (61.5-152.8) vs 63.4 mmol/L x pmol/L (52.9-98.2), p=0.02), and vaspin (0.15 μg/L (0.11-0.28) vs 0.45 μg/L (0.25-0.72), p=0.045) in the circulation. LEPR SNP (QQ vs RR) was associated with Adipo-IR (157.5 mmol/L x pmol/L (63.4-195.8) vs 75.3 mmol/L x pmol/L (58.1-148.8), p<0.05), MMP-9 (2.14 mg/L (1.72-3.20) vs 3.07 mg/L (2.27-5.96), p=0.048), and OPG (672.5 μg/L (572.0-748.3) vs 424.0 μg/L (330.0-592.5), p=0.04). Conclusion. These findings may be clinically useful for identifying a group of T2D who may have a LEP and/or LEPR gene variants, which may predispose this specific group to worse or better outcomes.  It is confirmed by new evidence the perspectives for introduction of personification therapy.

Effects of leptin and leptin receptor polymorphisms on metabolic parameters in type 2 diabetic patients