Several studies have shown that circulating sTNFR levels and/or polymorphisms in the TNF-RII gene are associated with heart failure, hypertension, obesity and insulin resistance, and differences in serum levels of a similar magnitude to those found in this study were shown to be clinically relevant in these conditions [47-52]. This evidence concerns the gene TNFRSF1B and obesity due to melanocortin 4 receptor deficiency.