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. 2024 Sep;103(10):999-1007.
doi: 10.1177/00220345241263320. Epub 2024 Aug 5.

The PerioGene North Study Uncovers Serum Proteins Related to Periodontitis

M Wänman  1 , S Betnér  2 , A Esberg  3 , C K Holm  1 , C Isehed  4   5 , A Holmlund  4   5 , P Palmqvist  6 , A Lövgren  7 , S Lindquist  1   8 , L Hänström  1 , U H Lerner  1   9 , E Kindstedt  1 , P Lundberg  1
Affiliations

The PerioGene North Study Uncovers Serum Proteins Related to Periodontitis

M Wänman et al. J Dent Res. 2024 Sep.

Abstract

The sequalae of periodontitis include irreversible degradation of tooth-supporting structures and circulatory spread of inflammatory mediators. However, the serum protein profile in periodontitis is not well described, which is partly attributable to the limited number of studies based on large and well-characterized periodontitis cohorts. This study aims to identify novel, circulating inflammation-related proteins associated with periodontitis within the PerioGene North case-control study, which includes 478 cases with severe periodontitis and 509 periodontally healthy controls. The serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and a panel of 45 inflammation-related proteins were analyzed using targeted proteomics. A distinguishable serum protein profile was evident in periodontitis cases. The protein pattern could separate cases from controls with a sensitivity of 0.81 and specificity of 0.81 (area under the curve = 0.87). Adjusted levels for hs-CRP and 24 of the 45 proteins were different between cases and controls. High levels of hs-CRP and matrix metalloproteinase-12, and low levels of epidermal growth factor (EGF) and oxidized low-density lipoprotein receptor 1 (OLR-1) were detected among the cases. Furthermore, the levels of C-C motif chemokine-19, granulocyte colony-stimulating factor-3 (CSF-3), interleukin-7 (IL-7), and hs-CRP were significantly higher in cases with a high degree of gingival inflammation. The levels of CSF-3 and tumor necrosis factor ligand superfamily member-10 TNFSF-10 were higher in cases with many deep periodontal pockets. The PerioGene North study includes detailed clinical periodontal data and uncovers a distinct serum protein profile in periodontitis. The findings of lower EGF and OLR-1 among the cases are highlighted, as this has not been presented before. The role of EGF and OLR-1 in periodontitis pathogenesis and as possible future biomarkers should be further explored.

Keywords: biomarkers; bone loss; epidemiology; inflammation; periodontal disease; proteomics.

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Conflict of interest statement

Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Serum protein profile analyses in PerioGene North cases and controls with (A) uniform manifold approximation and projection (UMAP) and (B) receiver-operating characteristic (ROC) curve. The ROC curve was based on logit scores from a logistic regression with all proteins as predictors. Logit scores were computed using a leave-one-out cross-validation approach.
Figure 2.
Figure 2.
Volcano plot showing significance and fold changes of inflammatory proteins according to (A) the nonadjusted regression model and (B) the regression model adjusted for age, sex, and ever smoked. The x-axis shows the log-fold change, where a positive value indicates higher levels in cases than in controls, whereas a negative value indicates lower levels. The y-axis shows the −log10 P value, where a high value indicate a low P value. The dashed line indicates the significance level at 0.05. Significant proteins with higher levels in cases are colored red, and significant proteins with lower levels are colored blue. Not significant proteins are colored gray.
Figure 3.
Figure 3.
Violin plots demonstrating the distribution of serum levels of (A) high-sensitivity C-reactive protein (hs-CRP), (B) epidermal growth factor (EGF), (C) matrix metalloproteinase–12 (MMP-12), and (D) oxidized low-density lipoprotein receptor 1 (OLR-1) in PerioGene North cases and controls. Integrated box plots show median pg/mL values and 25th and 75th percentiles as horizontal lines; whiskers indicate the 10th to 90th percentile. Outliers are plotted as dots. Receiver-operating characteristic (ROC) curve for prediction of cases and controls based on the serum levels of proteins.
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