In a prospective cohort study, 219 unselected subjects were monitored over a 4-year period, during which time they did not undergo any dental treatment and changes in periodontal pocket probing depth (as a measure of periodontitis) as compared to levels of salivary biomarkers and lifestyle factors; a multiple logistic model revealed that disease progression related to smoking habit and not the levels of any of some 9 protein biomarkers (IL-1β, MMP-8, MMP-9, lactoferrin, IgA, albumin, AST, LDH, and ALP) [144]. This evidence concerns the gene IL1B and periodontitis.