Smoking-induced changes in leptin serum levels and c/EBPalpha-related methylation status of the leptin core promotor during smoking cessation

Previous studies have provided evidence of an association between serum leptin levels and smoking as well as craving during smoking cessation. As promoter methylation also regulates leptin expression, we investigated the leptin gene promoter region of smokers before and after smoking cessation. Since leptin's core promoter region contains an essential c/EBPalpha transcription binding site, we narrowed our investigation to C-300 (-300 base pairs from the transcription start site) of that binding site. Female smokers showed hypermethylation of C-300 compared to non-smokers. Global methylation status is associated with higher craving and the degree of dependence in female smokers. Serum leptin levels in female smokers were significantly higher than in nonsmokers. These findings support previous results and, for the first time, point to a pathophysiological role of c/EBPalpha-related C-300 methylation in tobacco dependence.