Furthermore, various studies have demonstrated that dysregulated methylation of periodontium-associated genes CEMP 1, RUNX 2, IL 6 and TNF α is associated with systemic conditions such as obesity and osteoarthritis [40,41,42,43]; however, it remained unclear whether these methylation markers were detectable in saliva samples. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.