They showed a biologic gradient between severity of exposure and occurrence of disease and also proposed that periodontal disease, as chronic Gram-negative infection, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL-1β, PGE2, and TNF-α) leading to initiation and exacerbation of atherogenesis and thromboembolic events. This evidence concerns the gene TNF and periodontal disorder.