Polymorphism of salivary proteins and risk of periodontal diseases: A systematic review and meta-analysis of clinical studies.

Objectives: The present systematic review and meta-analysis aimed to assess the association between salivary protein polymorphisms and the risk of periodontal diseases (PD). Data: The review incorporated cross-sectional, case-control, retrospective/prospective cohort, and randomized controlled trials assessing the influence of salivary protein polymorphisms on the risk of PD development were included in this review. Sources: A thorough literature search was conducted across electronic databases, namely PubMed, Scopus, Embase, and Web of Science, without any restrictions on publication language and year. Study selection: A total of 168 studies were identified, of which 19 were eligible for inclusion. The risk of bias (RoB) assessment of the included studies was conducted at the methodological level. Results: A total of 16 studies were included. Polymorphism in the gene encoding TNF-alpha was found to be protective against gingivitis, while those encoding IL-1 alpha and IL-1 beta were associated with developing gingivitis. Of the 42 proteins investigated, various gene polymorphisms were identified as protective or risk factors for periodontitis. Protective genes include CFH, DNMT1, OPRM1, and TLR9. Conversely, certain salivary protein genes (e.g., CRP, ERN1, FAM5C, IDH2, LTA, TET2, MPA, NLRP3, TLR4) were associated with periodontitis risk. Notably, IL6, MMP9, and MUC7 genes showed no association with PD, while MMP13 was linked to early implant loss. Overall, the meta-analysis found a statistically significant association between salivary proteins' polymorphisms and risk of PD. Conclusions: Salivary protein polymorphisms significantly influence PD, revealing protective and risk-associated genotypes. Despite limitations, findings suggest therapeutic targets, emphasizing the complex geneticsperiodontal health interplay. Clinical significance: This study unveils salivary protein polymorphisms as pivotal factors in PD. Protective genes including CFH and TLR9, and risk-associated genes including CRP and TLR4, indicate a genetic basis for PD susceptibility.