Genetic risk variants implicate impaired maintenance and repair of periodontal tissues as causal for periodontitis—A synthesis of recent findings

Abstract

Periodontitis is a complex inflammatory disease in which the host genome, in conjunction with extrinsic factors, determines susceptibility and progression. Genetic predisposition is the strongest risk factor in the first decades of life. As people age, chronic exposure to the periodontal microbiome puts a strain on the proper maintenance of barrier function. This review summarizes our current knowledge on genetic risk factors implicated in periodontitis, derived (i) from hypothesis-free systematic whole genome-profiling studies (genome-wide association studies [GWAS] and quantitative trait loci [QTL] mapping studies), and independently validated through further unbiased approaches; (ii) from monogenic and oligogenic forms of periodontitis; and (iii) from syndromic forms of periodontitis. The genes include, but are not limited to, SIGLEC5, PLG, ROBO2, ABCA1, PF4, and CTSC. Notably, CTSC and PLG gene mutations were also identified in non-syndromic and syndromic forms of prepubertal and early-onset periodontitis. The functions of the identified genes in this review suggest that the pathways affected by the periodontitis-associated gene variants converge in functions involved in the maintenance and repair of structural integrity of the periodontal tissues. Particularly, these genes play a role in the healing of inflamed and ulcerated periodontal tissues, including roles in fibrinolysis, extrusion of cellular debris, extracellular matrix remodeling and angiogenesis. Syndromes that include periodontitis in their phenotype indicate that neutrophils play an important role in the regulation of inflammation in the periodontium. The established genetic susceptibility genes therefore collectively provide new insights into the molecular mechanisms and plausible causal factors underlying periodontitis.