Interaction between tumor necrosis factor-α gene -308G/A promoter and leptin receptor gene Lys656Asn single-nucleotide polymorphisms: effect on serum leptin concentrations.

BACKGROUND AND OBJECTIVE

The aim of our study was to investigate the interaction between the tumor necrosis factor-α (TNF-α) gene -308G/A promoter and the leptin receptor (LEPR) gene Lys656Asn polymorphisms and their effects on serum leptin levels in obese subjects.

DESIGN

A population of 237 obese patients was analyzed prospectively. Bipolar electrical bioimpedance, a biochemical analysis and serum concentrations of leptin and TNF-α were assessed.

RESULTS

The number of subjects with both mutations was 21 (8.86%). Subjects carrying the mutant LEPR genotype had higher concentrations of leptin than those with the wild-type LEPR genotype only when they also carried the mutant TNF-α genotype (G308A or A308A) (82.7 ± 63 vs. 147.6 ± 89 ng/ml; p < 0.05). In subjects with TNF-α G308G, multivariate analysis with leptin as a dependent variable revealed fat mass as an independent predictor in the model (F = 15.4; p < 0.05), with an increase of 4.1 ng/ml (95% CI 2.5-5.6) per kilogram of fat mass. The same was seen in subjects with TNF-α G308A and A308A genotypes, with an increase in leptin levels of 3.56 ng/ml (95% CI 1.8-5.3) per kilogram fat mass.

CONCLUSION

There is an interaction between TNF-α gene G308A promoter and LEPR gene Lys656Asn polymorphisms, with higher concentrations of leptin in the G308A and A308A genotypes combined with the mutant LEPR genotype.