Our results suggest that polymorphisms in the WRN gene might have a significant role regulating PAI-1 levels in healthy individuals and "normal states" as well as acute or chronic stress, obesity, aging, acute inflammation, among others, where characteristic high levels of insulin, TNF α and TGFβ, could favor PAI-1 high levels in carriers with polymorphic variants (C and F alleles), beyond the levels reached by carriers with other alleles (R and L alleles). The gene discussed is TGFB1; the disease is obesity due to melanocortin 4 receptor deficiency.