World Journal of Dentistry

Register      Login

VOLUME 15 , ISSUE 1 ( January, 2024 ) > List of Articles


Exploring the Epigenetic Landscape—Insights from Epigenomics in Periodontitis and Stress-related Health Implications: A Review

Smrithi Vishakha Varma, Sheeja Saji Varghese, Sajan Velayudhan Nair

Keywords : Chronic stress, Deoxyribonucleic acid methylation, Epigenetics, Epigenome, Histone modification, Immune response, Periodontitis

Citation Information : Varma SV, Varghese SS, Nair SV. Exploring the Epigenetic Landscape—Insights from Epigenomics in Periodontitis and Stress-related Health Implications: A Review. World J Dent 2024; 15 (1):72-78.

DOI: 10.5005/jp-journals-10015-2353

License: CC BY-NC 4.0

Published Online: 20-02-2024

Copyright Statement:  Copyright © 2024; The Author(s).


Background: The emerging field of epigenetics probes into the intricate modifications and information beyond the primary genetic code, investigating how gene function can be altered and inherited across cell generations without changes in deoxyribonucleic acid (DNA) sequences. This review specifically focuses on the epigenetic dimensions within two captivating areas—periodontitis and stress-related health implications. Aim: The aim of this literature review is to comprehensively delve into current research, shedding light on the interplay between epigenetics, oral health, and overall well-being. It particularly explores the epigenetic intricacies associated with periodontitis and stress-related conditions. Clinical significance: Despite the genetic complexity of periodontitis, the emergence of epigenetic biomarkers provides hope for early disease diagnosis and personalized management. Epigenetics, with established links to various diseases, including cancer, unfolds new therapeutic possibilities. While challenges persist in unraveling the intricacies of epigenetic regulation, it holds promise for advancing disease eradication, even for historically incurable conditions. Epigenetics stands as a hopeful avenue for treating stress-related disorders, although its full potential is still in the early stages of exploration.

  1. Widschwendter M, Jones PA. DNA methylation and breast carcinogenesis. Oncogene 2002;21(35):5462–5482. DOI: 10.1038/sj.onc.1205606
  2. Larsson L, Castilho RM, Giannobile WV. Epigenetics and its role in periodontal diseases: a state-of-the-art review. J Periodontol 2015;86(4):556–568. DOI: 10.1902/jop.2014.140559
  3. Meyle J, Chapple I. Molecular aspects of the pathogenesis of periodontitis. Periodontol 2000 2015;69(1):7–17. DOI: 10.1111/prd.12104. PMID: 26252398
  4. Koolhaas JM, Bartolomucci A, Buwalda B, et al. Stress revisited: a critical evaluation of the stress concept. Neurosci Biobehav Rev 2011;35(5):1291–1301. DOI: 10.1016/j.neubiorev.2011.02.003
  5. Stabholz A, Soskolne WA, Shapira L. Genetic and environmental risk factors for chronic periodontitis and aggressive periodontitis. Periodontol 2000 2010;53:138–153. DOI: 10.1111/j.1600-0757.2010.00340.x
  6. Issa JP. Age-related epigenetic changes and the immune system. Clin Immunol 2003;109(1):103–108. DOI: 10.1016/s1521-6616(03)00203-1
  7. Vivier E, Raulet DH, Moretta A, et al. Innate or adaptive immunity? The example of natural killer cells. Science 2011;331(6013):44–49. DOI: 10.1126/science.1198687
  8. Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res 2002;53(4):865–871. DOI: 10.1016/s0022-3999(02)00429-4
  9. Loos BG, Van Dyke TE. The role of inflammation and genetics in periodontal disease. Periodontol 2000 2020;83(1):26–39. DOI: 10.1111/prd.12297
  10. Smale ST. Transcriptional regulation in the innate immune system. Curr Opin Immunol 2012;24(1):51–57. DOI: 10.1016/j.coi.2011.12.008
  11. Carpenter S, Ricci EP, Mercier BC, et al. Post-transcriptional regulation of gene expression in innate immunity. Nat Rev Immunol 2014;14(6):361–376. DOI: 10.1038/nri3682
  12. Kornman KS. Mapping the pathogenesis of periodontitis: a new look. J Periodontol 2008;79(8 Suppl):1560–1568. DOI: 10.1902/jop.2008.080213
  13. Waddington CH. The epigenotype. 1942. Int J Epidemiol 2012;41(1):10–13. DOI: 10.1093/ije/dyr184
  14. Waddington CH. Towards a theoretical biology. Nature 1968;218(5141):525–527. DOI: 10.1038/218525a0
  15. Egger G, Liang G, Aparicio A, et al. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004;429(6990):457–463. DOI: 10.1038/nature02625
  16. Hamilton JP. Epigenetics: principles and practice. Dig Dis 2011;29(2):130–135. DOI: 10.1159/000323874
  17. Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 2012;13(2):97–109. DOI: 10.1038/nrg3142
  18. McGowan PO, Sasaki A, D'Alessio AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 2009;12(3):342–348. DOI: 10.1038/nn.2270
  19. Berger SL, Kouzarides T, Shiekhattar R, et al. An operational definition of epigenetics. Genes Dev 2009;23(7):781–783. DOI: 10.1101/gad.1787609
  20. Tsankova NM, Berton O, Renthal W, et al. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 2006;9(4):519–525. DOI: 10.1038/nn1659
  21. Turner BM. Defining an epigenetic code. Nat Cell Biol 2007;9(1):2–6. DOI: 10.1038/ncb0107-2
  22. Holliday R, Pugh JE. DNA modification mechanisms and gene activity during development. Science 1975;187(4173):226–232. DOI: 10.1126/science.187.4173.226
  23. Riggs AD. X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet 1975;14(1):9–25. DOI: 10.1159/000130315
  24. Szyf M. The early life social environment and DNA methylation: DNA methylation mediating the long-term impact of social environments early in life. Epigenetics 2011;6(8):971–978. DOI: 10.4161/epi.6.8.16793
  25. Héberlé É, Bardet AF. Sensitivity of transcription factors to DNA methylation. Essays Biochem 2019;63(6):727–741. DOI: 10.1042/EBC20190033
  26. Kohli RM, Zhang Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature 2013;502(7472):472–479. DOI: 10.1038/nature12750
  27. Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 2009;324(5929):929–930. DOI: 10.1126/science.1169786
  28. Fischle W, Tseng BS, Dormann HL, et al. Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature 2005;438(7071):1116–1122. DOI: 10.1038/nature04219
  29. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 2012;489(7414):57–74. DOI: 10.1038/nature11247
  30. Jenuwein T, Allis CD. Translating the histone code. Science 2001;293(5532):1074–1080. DOI: 10.1126/science.1063127
  31. Kimura H. Histone dynamics in living cells revealed by photobleaching. DNA Repair (Amst) 2005;4(8):939–950. DOI: 10.1016/j.dnarep.2005.04.012
  32. Peterson CL, Laniel MA. Histones and histone modifications. Curr Biol 2004;14(14): R546–R551. DOI: 10.1016/j.cub.2004.07.007
  33. Zaratiegui M, Irvine DV, Martienssen RA. Noncoding RNAs and gene silencing. Cell 2007;128(4):763–776. DOI: 10.1016/j.cell.2007.02.016
  34. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390(10100):1211–1259. DOI: 10.1016/S0140-6736(17)32154-2
  35. Sanz M, D'Aiuto F, Deanfield J, et al. European workshop in periodontal health and cardiovascular disease. Eur Heart J Suppl 2010;12(Suppl B):B3–B12 DOI: 10.1093/eurheartj/suq003
  36. Jin LJ, Lamster IB, Greenspan JS, et al. Global burden of oral diseases: emerging concepts, management and interplay with systemic health. Oral Dis 2016;22(7):609–619. DOI: 10.1111/odi.12428
  37. Nibali L, Bayliss-Chapman J, Almofareh SA, et al. What Is the heritability of periodontitis? A systematic review. J Dent Res 2019;98(6):632–641. DOI: 10.1177/0022034519842510
  38. Michalowicz BS, Aeppli DP, Kuba RK, et al. A twin study of genetic variation in proportional radiographic alveolar bone height. J Dent Res 1991;70(11):1431–1435. DOI: 10.1177/00220345910700110701
  39. Mucci LA, Björkman L, Douglass CW, et al. Environmental and heritable factors in the etiology of oral diseases–a population-based study of Swedish twins. J Dent Res 2005;84(9):800–805. DOI: 10.1177/154405910508400904
  40. Chatzopoulos GS, Doufexi AE, Kouvatsi A. Clinical response to non-surgical periodontal treatment in patients with interleukin-6 and interleukin-10 polymorphisms. Med Oral Patol Oral Cir Bucal 2017;22(4): e446–e457. DOI: 10.4317/medoral.21795
  41. Chatzopoulos GS, Doufexi AE, Zarenti S, et al. Periodontal disease progression and gene polymorphisms: results after 3 years of active periodontal treatment. Minerva Dent Oral Sci 2022;71(6):329–338. DOI: 10.23736/S2724-6329.22.04709-X
  42. Hernández HG, Hernández-Castañeda AA, Pieschacón MP, et al. ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: epigenome-wide DNA methylation pilot study. J Periodontal Res 2021;56(4):710–725. DOI: 10.1111/jre.12868
  43. Kurushima Y, Tsai PC, Castillo-Fernandez J, et al. Epigenetic findings in periodontitis in UK twins: a cross-sectional study. Clin Epigenetics 2019;11(1):27. DOI: 10.1186/s13148-019-0614-4
  44. Hart TC. Genetic considerations of risk in human periodontal disease. Curr Opin Periodontol 1994:3–11. PMID: 8032464.
  45. Schafer AS, Jepsen S, Loos BG. Periodontal genetics: a decade of genetic association studies mandates better study designs. J Clin Periodontol 2011;38(2):103–107. DOI: 10.1111/j.1600-051X.2010.01653.x
  46. Loos BG, Velden UV. Clinical Periodontology and Implant Dentistry, 4th edition. Jaypee Brothers; 2003. pp. 387–399.
  47. Michalowicz BS, Aeppli D, Virag JG, et al. Periodontal findings in adult twins. J Periodontal 1991;62(5):293–299. DOI: 10.1902/jop.1991.62.5.293
  48. Larsson L. Current concepts of epigenetics and its role in periodontitis. Curr Oral Health Rep 2017;4(4):286–293. DOI: 10.1007/s40496-017-0156-9
  49. Khouly I, Braun RS, Ordway M, et al. The role of DNA methylation and histone modification in periodontal disease: a systematic review. Int J Mol Sci 2020;21(17):6217. DOI: 10.3390/ijms21176217
  50. Williams SD, Hughes TE, Adler CJ, et al. Epigenetics: a new frontier in dentistry. Aust Dent J 2014;59(Suppl 1):23–33. DOI: 10.1111/adj.12155
  51. De Souza AP, Planello AC, Marques MR, et al. High-throughput DNA analysis shows the importance of methylation in the control of immune inflammatory gene transcription in chronic periodontitis. Clin Epigenet 2014;6(1):15. DOI: 10.1186/1868-7083-6-15
  52. Li X, Lu J, Teng W, et al. Quantitative evaluation of MMP-9 and TIMP-1 promoter methylation in chronic periodontitis. DNA Cell Biol 2018;37(3):168–173. DOI: 10.1089/dna.2017.3948
  53. Martins MD, Jiao Y, Larsson L, et al. Epigenetic modifications of histones in periodontal disease. J Dent Res 2016;95(2):215–222. DOI: 10.1177/0022034515611876
  54. Zhu ZX, Liu Y, Wang J, et al. A novel lncRNA-mediated epigenetic regulatory mechanism in periodontitis. Int J Biol Sci 2023;19(16):5187–5203. DOI: 10.7150/ijbs.87977
  55. Loos BG, Papantonopoulos G, Jepsen S, et al. What is the contribution of genetics to periodontal risk? Dent Clin North Am 2015;59(4):761–780. DOI: 10.1016/j.cden.2015.06.005
  56. Radley JJ, Kabbaj M, Jacobson L, et al. Stress risk factors and stress-related pathology: neuroplasticity, epigenetics and endophenotypes. Stress 2011;14(5):481–497. DOI: 10.3109/10253890.2011.604751
  57. Karatsoreos IN, McEwen BS. Annual research review: the neurobiology and physiology of resilience and adaptation across the life course. J Child Psychol Psychiatry 2013;54(4):337–347. DOI: 10.1111/jcpp.12054
  58. Yehuda R, Bierer LM. Transgenerational transmission of cortisol and PTSD risk. Prog Brain Res 2008;167:121–135. DOI: 10.1016/S0079-6123(07)67009-5
  59. Goyal S, Gupta G, Thomas B, et al. Stress and periodontal disease: the link and logic! Ind Psychiatry J 2013;22(1):4–11. DOI: 10.4103/0972-6748.123585
  60. Warren KR, Postolache TT, Groer ME, et al. Role of chronic stress and depression in periodontal diseases. Periodontol 2000 2014;64(1):127–138. DOI: 10.1111/prd.12036
  61. Lu XT, Zhao YX, Zhang Y, et al. Psychological stress, vascular inflammation, and atherogenesis: potential roles of circulating cytokines. J Cardiovasc Pharmacol 2013;62(1):6–12. DOI: 10.1097/FJC.0b013e3182858fac
  62. Hilgert JB, Hugo FN, Bandeira DR, et al. Stress, cortisol, and periodontitis in a population aged 50 years and over. J Dent Res 2006;85(4):324–328. DOI: 10.1177/154405910608500408
  63. Cakmak O, Tasdemir Z, Aral CA, et al. Gingival crevicular fluid and saliva stress hormone levels in patients with chronic and aggressive periodontitis. J Clin Periodontol 2016;43(12):1024–1031. DOI: 10.1111/jcpe.12614
  64. Jaiswal R, Shenoy N, Thomas B. Evaluation of association between psychological stress and serum cortisol levels in patients with chronic periodontitis - estimation of relationship between psychological stress and periodontal status. J Indian Soc Periodontol 2016;20(4):381–385. DOI: 10.4103/0972-124X.193165
  65. Mousavijazi M, Naderan A, Ebrahimpoor M, et al. Association between psychological stress and stimulation of inflammatory responses in periodontal disease. J Dent (Tehran) 2013;10(1):103–111. PMID: 23724208.
  66. Goyal S, Jajoo S, Nagappa G, et al. Estimation of relationship between psychosocial stress and periodontal status using serum cortisol level: a clinico-biochemical study. Indian J Dent Res 2011;22(1):6–9. DOI: 10.4103/0970-9290.79966
  67. Slatkin M. Epigenetic inheritance and the missing heritability problem. Genetics 2009;182(3):845–850. DOI: 10.1534/genetics.109.102798
  68. Tsankova N, Renthal W, Kumar A, et al. Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci 2007;8(5):355–367. DOI: 10.1038/nrn2132
  69. Siegmund KD, Connor CM, Campan M, et al. DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS One 2007;2(9):e895. DOI: 10.1371/journal.pone.0000895
  70. Cirillo N, Prime SS. Keratinocytes synthesize and activate cortisol. J Cell Biochem 2011;112(6):1499–1505. DOI: 10.1002/jcb.23081
  71. Dhabhar FS, McEwen BS. Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: a potential role for leukocyte trafficking. Brain Behav Immun 1997;11(4):286–306. DOI: 10.1006/brbi.1997.0508
  72. Baybutt HN, Holsboer F. Inhibition of macrophage differentiation and function by cortisol. Endocrinology 1990;127(1):476–480. DOI: 10.1210/endo-127-1-476
  73. Gatti G, Cavallo R, Sartori ML, et al. Inhibition by cortisol of human natural killer (NK) cell activity. J Steroid Biochem 1987;26(1):49–58. DOI: 10.1016/0022-4731(87)90030-6
  74. Gallacher DV, Petersen OH. Stimulus-secretion coupling in mammalian salivary glands. Int Rev Physiol 1983;28:1–52. PMID: 6307913.
  75. Cohen-Cole SA, Cogen RB, Stevens AW, et al. Psychiatric, psychosocial, and endocrine correlates of acute necrotizing ulcerative gingivitis (trench mouth): a preliminary report. Psychiatr Med 1983;1(2):215–225. PMID: 6599850.
  76. Neupane SP, Virtej A, Myhren LE, et al. Biomarkers common for inflammatory periodontal disease and depression: a systematic review. Brain Behav Immun Health 2022;21:100450. DOI: 10.1016/j.bbih.2022.100450
  77. Walton E, Hass J, Liu J, et al. Correspondence of DNA methylation between blood and brain tissue and its application to schizophrenia research. Schizophr Bull 2016;42(2):406–414. DOI: 10.1093/schbul/sbv074
  78. Cho YD, Kim WJ, Ryoo HM, et al. Current advances of epigenetics in periodontology from ENCODE project: a review and future perspectives. Clin Epigenetics 2021;13(1):92. DOI: 10.1186/s13148-021-01074-w
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.