Association between circulating 25‐hydroxyvitamin D metabolites and periodontitis: Results from the NHANES 2009–2012 and Mendelian randomization study

This study sought to investigate associations of 25-hydroxyvitamin D (25(OH)D) metabolites with periodontitis and to assess causality using Mendelian randomization (MR).This study included 7246 participants of the National Health and Nutrition Examination Survey, 2009-2012. The association of periodontitis with 25(OH)D metabolites was assessed using multivariable logistic regression analysis. Two-sample MR for 25(OH)D, 25(OH)D3 , and C3-epi-25(OH)D3 with periodontitis (n = 17,353 cases/28,210 controls) was conducted. The principal analysis employed the inverse-variance-weighted (IVW) approach. We controlled for horizontal pleiotropy using five additional methods.Based on the observational study, each 1-point increase in standard deviation of 25(OH)D lowered the risk of periodontitis by 15% (OR = 0.85, 95% confidence interval [CI]: 0.78-0.93, p = .006) after multivariable adjustment. A similar relationship was observed between 25(OH)D3 and periodontitis (OR = 0.88, 95% CI: 0.80-0.97, p = .031). Furthermore, a potential non-linear association was found between periodontitis and both 25(OH)D and 25(OH)D3 . However, C3-epi-25(OH)D3 was not found to be associated with periodontitis risk. IVW-MR showed that periodontitis risk was not significantly associated with genetically increased levels of 25(OH)D (OR = 1.02, 95% CI: 0.90-1.16, p = .732), 25(OH)D3 (OR = 1.04, 95% CI: 0.93-1.17, p = .472), or C3-epi-25(OH)D3 (OR = 1.11, 95% CI: 0.87-1.41, p = .400). The pleiotropy-robust MR approaches yielded similar results after we had eliminated the variants with horizontal pleiotropy risk.Cross-sectional observational analysis identified significant relationships between periodontitis with 25(OH)D metabolites, while findings based on MR study did not support a causal role.