It is also known that cyclooxygenase 2 (COX-2), whose expression by force-stimulated periodontal ligament fibroblasts was significantly enhanced in presence of nicotine,10 is a target gene of HIF-1α,52 which is the central mediating factor for the adaptation of tissues to hypoxic states.53 In addition, synergistically enforced hypoxic conditions within the periodontal ligament may favor the growth of the mostly anaerobic periodontal pathogens, responsible for bacterially induced periodontitis.13 The gene discussed is HIF1A; the disease is periodontitis.