https://doi.org/10.1007/s00392-025-02625-4
1Uniklinik RWTH Aachen Med. Klinik I - Kardiologie, Angiologie und Internistische Intensivmedizin Aachen, Deutschland; 2Klinik für Zahnärztliche Prothetik und Biomaterialien Aachen, Deutschland; 3Uniklinik RWTH Aachen Institut für Molekulare Herz-Kreislaufforschung (IMCAR) Aachen, Deutschland; 4Klinik für Kieferorthopädie Aachen, Deutschland
Background
Systemic inflammation has been linked to dental health, with the complement system playing a significant role in this cross-talk. Indeed, experimental studies suggest that complement activation is associated with various oral pathologies. However, it remains uncertain whether systemic inflammation drives poor oral health or if deteriorating oral health is a contributing factor to systemic inflammation.
Aim
To investigate the role of inflammation and the complement system on oral health in the UK Biobank.
Methods and results
We analysed data from 520,784 UK Biobank participants with available information on oral health and inflammation (i.e. hsCRP). Stratification of hsCRP into tertiles (hsCRP1st: 0.51±0.2 hsCRP2nd: 1.45±0.38 hsCRP3rd: 6.42±6.84) demonstrated a close link between the Complement C3 and Inflammation (p < 0.001). In addition, patients within the 3rdhsCPR tertile were significantly more affected by poor oral health than patients in the 1st tertile (1st 36% vs 3rd: 47%, p < 0.001) with the need for Dentures being the most common oral health problem (1st 13% vs 3rd: 24%, p < 0.001). Stratification of oral health by hsCRP- and Complement C3 tertiles showed a stepwise increase in odds ratio up to 1.6 ([95%CI 1.5 – 1.7]; i.e. fully adjusted for biomarkers, socioeconomic- and CV risk factors) for patients within the highest tertiles (p for interaction 0.0087).
This indicated a synergism between Complement C3 and hsCRP. To assess the directionality of this association, we investigated the impact of the well-established SNP rs2228145, which is linked to reduced IL-6 signalling and thereby reduced systemic inflammation. Indeed, patients with the homozygous variant of rs2228145 (C/C) had lower levels of hsCRP (A/A:2.97±4.92 mg/dL; A/C: 2.76±4.67mg/dL; C/C:2.47±4.40mg/dL; p < 0.001) and Complement C3 (A/A:0.07±0.51; A/C: 0.04±0.47; C/C:0.03±0.49 p < 0.001). Importantly, individuals with the C/C genotype also had a 5% lower risk of poor oral health (OR 0.95, 95% CI: 0.94 – 0.97, p < 0.001), supporting a causal role for inflammation in poor oral health outcomes.
Conclusion
Our findings underscore the importance of systemic inflammation and Complement C3 as contributing risk factors for poor oral health in the UK Biobank population. Genetic evidence further supports a causal relationship between inflammation and oral health, suggesting that anti-inflammatory interventions may benefit oral health outcomes.