Association of antihypertensive drugs with periodontitis: a comprehensive drug-target Mendelian randomization study

Objective: The aim of this study was to elucidate the nuanced interactions between antihypertensive medications and the risk of periodontitis using the Mendelian randomization analysis method. Method and materials: The study adopted a drug-target Mendelian randomization method to assess the long-term effects of nine antihypertensive drug categories on the risk of periodontitis in both acute and chronic cases. Genetic variants located in or near genes relevant to the targets of these drugs and associated with systolic blood pressure (SBP) were selected to simulate the influence of antihypertensive treatments. Genetic information on SBP and periodontitis susceptibility was extracted from extensive genome-wide association studies for both acute and chronic conditions. Additionally, a secondary analysis was conducted using expression quantitative trait loci for the genes of interest as alternative proxies. Colocalization analysis was performed to explore shared variants between antihypertensive drugs and periodontitis. Results: The analysis revealed that the use of angiotensin-converting enzyme inhibitors with an increased risk of acute periodontitis (odds ratio (OR) [95% confidence interval] 1.43 [1.11, 1.85] per 1 mmHg reduction in SBP; P=5.93 x10-3) and loop diuretics with a decreased risk of chronic periodontitis (OR 0.94 [0.90, 0.98]; P=2.94 x 10-3). Moreover, genetically mimicking the use of a suggestive protective effect of thiazides and related diuretics on acute periodontitis was observed in both acute (OR 0.95 [0.90, 0.99]; P=.021) and chronic (OR 0.98 [0.97, 1.00]; P=.045) periodontitis. Colocalization analysis re- vealed antihypertensive drugs and periodontitis shared causal variants in ACE and SLC12A2 locus. Conclusion: The research indicates that loop diuretics might decrease the risk of periodontitis, while angiotensin-converting enzyme inhibitors could heighten the risk. Further investigations are required to evaluate the potential of reusing antihypertensive drugs for periodontitis prevention. (Quintessence Int 2024;55:814-823; doi: 10.3290/1qi.b5754882)