ArticleClinical oral investigations2025
Comparative evaluation of ferroptosis markers NCOA4, ACSL4, and Nrf2 in periodontitis with and without type 2 diabetes mellitus: a case-control study.
Article in Clinical oral investigations, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimThe Nuclear Receptor Coactivator 4 (NCOA4)-mediated ferritinophagy and the Acyl-CoA synthetase long-chain family member 4 (ACSL4)-mediated lipid peroxidation promote ferroptosis. Nuclear factor erythroid-2 related factor-2 (Nrf2), a transcription factor, controls antioxidants, detoxifying enzymes, and ferroptosis. The concerted activity of NCOA4, ACSL4, and Nrf2 in periodontitis associated with or without T2DM needs exploration. MATERIALS AND
methodsForty-two patients were recruited and categorized into 3 groups: Group I: systemically and periodontally healthy (PH, n = 14); Group II: Stage III/IV Periodontitis (PD, n = 14); Group III: Stage III/IV Periodontitis with uncontrolled Type 2 Diabetes mellitus (T2DM + DM, n = 14). The site-specific periodontal clinical parameters were recorded. Gingival tissue biopsies were evaluated for gene expression of NCOA4, Nrf2, and ACSL4 by real time -PCR.
resultsIn groups II and III, NCOA4 expression increased by 10.07 ± 9.15 and 9.40 ± 6.29-fold, respectively, whereas ACSL4 expression increased by 3.23 ± 2.53 and 2.03 ± 2.22-fold, respectively, compared to group I (P < 0.05). Nrf2 expression decreased in groups II (0.36 ± 0.39) and III (0.83 ± 0.89) compared to group I, with the least expression in group II. In the total sample analysis, NCOA4 FC and Nrf2 CT showed a significant positive correlation with all clinical parameters and with each other (P < 0.05). There was a significant positive correlation (P < 0.05) between NCOA4 FC and ACSL4 CT (P < 0.05). In group II, NCOA4 CT had significant positive and negative correlations with Nrf2 FC and ACSL4 FC values, respectively (P < 0.05). The diagnostic accuracy of NCOA4 and Nrf2 in differentiating between periodontal health and periodontitis was 89% (AUC = 0.96) and 71% (AUC = 0.60), respectively. Likewise, NCOA4 and Nrf2 demonstrated diagnostic accuracy of 67.8% (AUC = 0.73) and 78.5% (AUC = 0.85) in differentiating between diabetic periodontitis and periodontal health, respectively.
conclusionsFerroptosis in the progression of periodontitis and diabetes-associated periodontitis may be linked to dysregulated expressions of the NCOA4, ACSL4, and Nrf2 genes. However, additional investigation is required to fully comprehend the findings.
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