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

J Clin Periodontol . 2022 Oct 23. doi: 10.1111/jcpe.13736. Online ahead of print. Abstract Aim: This study sought to investigate associations of 25(OH)D metabolites with periodontitis, and to assess causality using Mendelian randomization (MR). Methods: This study included 7,246 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. 2-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 was inverse-variance-weighted approach. We controlled for horizontal pleiotropy using five additional methods. Results: 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% CI: 0.78-0.93, P = 0.006) after multivariable adjustment. A similar relationship was observed between 25(OH)D3 and periodontitis (OR = 0.88, 95% CI: 0.80-0.97, P = 0.031). Furthermore, a potential nonlinear association was found between periodontitis with 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 = 0.732), 25(OH)D3 (OR = 1.04, 95% CI: 0.93-1.17, P = 0.472), and C3-epi-25(OH)D3 (OR = 1.11, 95% CI: 0.87-1.41, P = 0.400). The pleiotropy-robust MR approaches yielded similar results after we had eliminated the variants with horizontal pleiotropy risk. Conclusion: Cross-sectional observational analysis identified significant relationships between periodontitis with 25(OH)D metabolites, while findings based on MR study do not support a causal role. This article is protected by copyright. All rights reserved.