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      An observation on the severity of periodontal disease in past cigarette smokers suffering from rheumatoid arthritis- evidence for a long-term effect of cigarette smoke exposure?

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          Abstract

          Background

          Rheumatoid arthritis (RA) and cigarette smoking are both risk factors for periodontal disease (PD). Previous research suggests that systemic inflammatory conditions and cigarette smoking may act in synergy, and their co-occurrence leads to a much higher risk of developing severe stage PD than what the combination of their individual risks would suggest. We originally sought to test this in the case of RA, but it turned out that the majority of our patients were former smokers, who smoked for prolonged periods in the past. For that reason, we decided to shift our focus toward the possible effects of past chronic cigarette smoke exposure.

          Methods

          The data of 73 RA patients and 77 healthy controls were analyzed. The participants received a full-mouth periodontal examination to determine their periodontal status. Rheumatological indices and data on past tobacco use were also recorded. Both the patient and the control groups were divided into former smoker and non-smoker subgroups for the analyses. Non-smoker controls were used as the reference group.

          Results

          In the control group, smoking in history increased the odds of developing both the moderate and the severe stages of PD, but the change was not statistically significant. RA significantly, increased the odds of developing both stages in itself, but the highest odds were seen in the former smoker RA group.

          Conclusion

          Based on this surprising observation of ours, we hypothesize that chronic cigarette smoke might bring about permanent changes in the periodontal tissues, leading to their hypersensitivity to inflammatory challenges.

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          Most cited references28

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          Cigarette smoking and DNA methylation

          DNA methylation is the most studied epigenetic modification, capable of controlling gene expression in the contexts of normal traits or diseases. It is highly dynamic during early embryogenesis and remains relatively stable throughout life, and such patterns are intricately related to human development. DNA methylation is a quantitative trait determined by a complex interplay of genetic and environmental factors. Genetic variants at a specific locus can influence both regional and distant DNA methylation. The environment can have varying effects on DNA methylation depending on when the exposure occurs, such as during prenatal life or during adulthood. In particular, cigarette smoking in the context of both current smoking and prenatal exposure is a strong modifier of DNA methylation. Epigenome-wide association studies have uncovered candidate genes associated with cigarette smoking that have biologically relevant functions in the etiology of smoking-related diseases. As such, DNA methylation is a potential mechanistic link between current smoking and cancer, as well as prenatal cigarette-smoke exposure and the development of adult chronic diseases.
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            Periodontal disease and diabetes mellitus: a two-way relationship.

            Severe periodontal disease often coexists with severe diabetes mellitus. Diabetes is a risk factor for severe periodontal disease. A model is presented whereby severe periodontal disease increases the severity of diabetes mellitus and complicates metabolic control. We propose that an infection-mediated upregulation cycle of cytokine synthesis and secretion by chronic stimulus from lipopolysaccharide (LPS) and products of periodontopathic organisms may amplify the magnitude of the advanced glycation end product (AGE)-mediated cytokine response operative in diabetes mellitus. In this model, the combination of these 2 pathways, infection and AGE-mediated cytokine upregulation, helps explain the increase in tissue destruction seen in diabetic periodontitis, and how periodontal infection may complicate the severity of diabetes and the degree of metabolic control, resulting in a 2-way relationship between diabetes mellitus and periodontal disease/infection. This proposed dual pathway of tissue destruction suggests that control of chronic periodontal infection is essential for achieving long-term control of diabetes mellitus. Evidence is presented to support the hypothesis that elimination of periodontal infection by using systemic antibiotics improves metabolic control of diabetes, defined by reduction in glycated hemoglobin or reduction in insulin requirements.
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              Periodontitis in RA-the citrullinated enolase connection.

              Autoimmunity in rheumatoid arthritis (RA) is characterized by an antibody response to citrullinated proteins. Two of the risk factors for RA-HLA-DRB1 shared epitope alleles and smoking-are also associated with periodontitis, which is largely, but not exclusively, caused by Porphyromonas gingivalis infection. Furthermore, RA and periodontitis have a similar pathophysiology, characterized by destructive inflammation. The citrullination of proteins by P. gingivalis and the subsequent generation of autoantigens that drive autoimmunity in RA represents a possible causative link between these two diseases. Antibodies directed towards the immunodominant epitope of human citrullinated α-enolase cross-react with a conserved sequence on citrullinated P. gingivalis enolase. On the basis of this cross-reactivity, in this Perspectives article we explore the hypothesis of molecular mimicry in the etiology of RA, with citrullinated enolase as the specific antigen involved.
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                Author and article information

                Contributors
                +3662545283 , antal.mark@stoma.szote.u-szeged.hu
                battancs.emese@stoma.szote.u-szeged.hu
                bocskai.marta@med.u-szeged.hu
                braunitzergabor@gmail.com
                kovacs.laszlo@med.u-szeged.hu
                Journal
                BMC Oral Health
                BMC Oral Health
                BMC Oral Health
                BioMed Central (London )
                1472-6831
                10 May 2018
                10 May 2018
                2018
                : 18
                : 82
                Affiliations
                [1 ]ISNI 0000 0001 1016 9625, GRID grid.9008.1, Faculty of Dentistry, Department of Aesthetic and Operative Dentistry, , University of Szeged, ; 6720 Tisza Lajos körút, Szeged, 64 Hungary
                [2 ]ISNI 0000 0001 1016 9625, GRID grid.9008.1, Faculty of Medicine, Department of Rheumatology and Immunology, , University of Szeged, ; 6725 Kálvária sugárút, Szeged, 57 Hungary
                [3 ]Laboratory for Perception & Cognition and Clinical Neuroscience, Nyírő Gyula Hospital, 1135 Lehel utca, Budapest, 59 Hungary
                Article
                531
                10.1186/s12903-018-0531-5
                5946453
                29747598
                40e03eba-eb9b-4739-9184-b6d0a8d4161a
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 4 May 2017
                : 17 April 2018
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Dentistry
                rheumatoid arthritis,periodontal disease,chronic inflammation,late sequelae,tobacco smoking

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