Genetic polymorphisms associated with periodontitis in Japanese populations: A comprehensive review of pathways, interactions, and clinical implications

Elisabetta Ferrara; Alessandro D'Albenzio; Biagio Rapone; Francesco Mastrocola; Giovanna Murmura

doi:10.1016/j.meegid.2025.105781

Genetic polymorphisms associated with periodontitis in Japanese populations: A comprehensive review of pathways, interactions, and clinical implications

Infect Genet Evol. 2025 Jun 14:133:105781. doi: 10.1016/j.meegid.2025.105781. Online ahead of print.

Authors

Elisabetta Ferrara¹, Alessandro D'Albenzio², Biagio Rapone³, Francesco Mastrocola⁴, Giovanna Murmura⁵

Affiliations

¹ Department of Human, Giuridical and Economic Sciences, Telematic University Leonardo Da Vinci, Torrevecchia Teatina, 66100 Chieti, Italy. Electronic address: elisabetta.ferrara@unidav.it.
² Complex Operative Unit of Pathological Addiction, Addiction Service, Chieti, Italy.
³ Department of Basic Medical Sciences, Neurosciences and Sense Organs, "Aldo Moro" University of Bari, Bari, Italy.
⁴ Department of Human, Giuridical and Economic Sciences, Telematic University Leonardo Da Vinci, Torrevecchia Teatina, 66100 Chieti, Italy.
⁵ Unit of Prosthodontics, Department of Innovative Technologies in Medicine and Dentistry, University D'Annunzio of Chieti- Pescara, 66100 Chieti, Italy.

PMID: 40523434
DOI: 10.1016/j.meegid.2025.105781

Abstract

Periodontitis is a chronic inflammatory disease affecting the supporting structures of teeth, with increasing evidence supporting a significant genetic component in disease susceptibility. This comprehensive review evaluated the associations between genetic polymorphisms and periodontitis in Japanese populations. This narrative review synthesizes available evidence without employing meta-analytical methods. Analysis of relevant studies revealed population-specific genetic architecture, with patterns that suggest possible differences from those observed in Western populations. Significant associations were identified for Japanese populations in immune-related genes (*IL1RN* VNTR: OR 3.40 in G-EOP; *IL1B* -511: OR 1.72 in chronic periodontitis), immunoreceptors (*FCGR3A*-158 V: OR 2.03 in severe chronic periodontitis), tissue remodeling genes (*MMP1* -1607 1G/2G: OR 1.95 in chronic periodontitis), and vitamin D pathway genes (*VDR* +1056 T/C: OR 2.45 in chronic periodontitis). Novel genetic associations with exceptionally strong effect sizes were identified with *ADGRG6* (formerly GPR126) (rs536714306: OR 9.09), *MAEA* (rs6815464: OR 3.73), and *CSF1* genes, expanding our understanding beyond traditional inflammatory pathways. Gene-gene interactions, particularly between *VDR* and *FCGR3B* polymorphisms (composite genotype: OR 5.93), demonstrated substantially stronger associations with periodontitis than individual polymorphisms alone. Protective genetic variants, including *FCGR3B*-NA1 allotype in elderly individuals and *IL1B* rs16944 GA genotype, highlight the concept of genetic resilience. Genetic associations differ markedly between aggressive and chronic forms of periodontitis, with stronger associations typically observed in aggressive/early-onset disease. These findings may contribute to improved risk assessment strategies and personalized approaches to periodontitis prevention and treatment in Japanese individuals, emphasizing the importance of population-specific genetic profiling in periodontal medicine.

Keywords: Gene polymorphism; Japanese population; Periodontitis.

Publication types

Review