Abstract:

In earlier days, researchers were concluding the origin of the disease based on genetic or environmental factors. In the past few years, Epigenetics has been considered as source of certain diseases which could not be ascertained by traditional sources. Recently, more focus has been given to epigenetics, for diseases for which autoimmune disorders, Cardiovascular disease, Cancer, Diabetes, neurodegenerative etc. The original and categorical descriptions of epigenetic alterations, as well as the function of epigenetics in biology and the relationship between epigenetics and the environment, are clarified in the current review. It appears that the significance of epigenetics in human disease is examined by concentrating on a few diseases with complex characteristics. Finally, we have provided an outlook for this field’s future. This review explains the relationship between the epigenetic markers and the environment which influences diabetes.

References:

[1].   Armstrong, L., 2014, Epigenetics. London: Garland Science.

[2].   Berger, S. L., Kouzarides T., Shiekhattar R., Shilatifard A., 2009, An operational definition of epigenetics. Genes Dev., 1;23 (7), 781–3. doi: 10.1101/gad.1787609.

[3].   Moosavi, A., Ardekani, A. M., 2016, Role of epigenetics in biology and human diseases. Iran. Biomed. J., 20, 246–258.

[4].   Jayaraman, S., Natarajan, S. R., Ponnusamy, B., Veeraraghavan, V. P., Jasmine, S., 2023, Unlocking the potential of beta sitosterol: Augmenting the suppression of oral cancer cells through extrinsic and intrinsic signalling mechanisms. The Saudi Dental Journal, 35(8), pp.1007-1013.

[5].   Holliday, R., 2006, Epigenetics: a historical overview. Epigenetics, 1, 76– 80.

[6].   Pinel, C., Prainsack, B., McKevitt, C., 2019, Markers as mediators: A review and synthesis of epigenetics literature. Biosocieties., 10;13(1), 276-303. doi: 10.1057/s41292-017-0068-x.

[7].   Cavalli, G., Heard E., 2019, Advances in epigenetics link genetics to the environment and disease. Nature, 571(7766), 489–499. doi: 10.1038/s41586-019-1411-0.

[8].   Sruthi, M. A., Mani, G., Ramakrishnan, M. and Selvaraj, J., 2023, Dental caries as a source of Helicobacter pylori infection in children: An RT‐PCR study. International Journal of Paediatric Dentistry, 33(1), pp.82-88.

[9].   Bansal, A., Pinney, S. E., 2017, DNA methylation and its role in the pathogenesis of diabetes. Pediatr Diabetes, 18(3), 167–177. doi: 10.1111/pedi.12521.

[10].  Jayaraman, S., Natarajan, S. R., Veeraraghavan, V. P., and Jasmine, S., 2023, Unveiling the anti-cancer mechanisms of calotropin: Insights into cell growth inhibition, cell cycle arrest, and metabolic regulation in human oral squamous carcinoma cells (HSC-3). Journal of Oral Biology and Craniofacial Research, 13(6), pp.704-713.

[11].  Rönn, T., Ling, C., 2015, DNA methylation as a diagnostic and therapeutic target in the battle against Type 2 diabetes. Epigenomics. 7(3):451-60. doi: 10.2217/epi.15.7.

[12].  Szabó, M., Máté, B., Csép, K., Benedek, T., 2018, Epigenetic Modifications Linked to T2D, the Heritability Gap, and Potential Therapeutic Targets. Biochem Genet. 2018 56(6):553-574. doi: 10.1007/s10528-018-9863-8.

[13].  Ling, C., 2020, Epigenetic regulation of insulin action and secretion - role in the pathogenesis of type 2 diabetes. J Intern Med. 288(2):158-167. doi: 10.1111/joim.13049.

[14].  Jin, B., Li, Y., Robertson, K. D., 2011, DNA methylation: superior or subordinate in the epigenetic hierarchy? Genes Cancer, 2(6), 607–17. doi: 10.1177/1947601910393957.

[15].  Ling C., 2020, Epigenetic regulation of insulin action and secretion - role in the pathogenesis of type 2 diabetes, J Intern Med, 288(2), 158–167.

[16].  Juvinao-Quintero, D. L., Marioni, R. E., Ochoa-Rosales, C., Russ, T. C., Deary, I. J., Van Meurs, J. B., Voortman, T., Hivert, M. F., Sharp, G. C., Relton, C. L., and Elliott, H. R., 2021, DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts, Clinical epigenetics, 13, 1–14.

[17].  Raciti G. A., Desiderio, A., Longo, M., Leone, A., Zatterale, F., Prevenzano, I., Miele, C., Napoli, R., Beguinot, F., 2021, DNA Methylation and Type 2 Diabetes: Novel Biomarkers for Risk Assessment? Int J Mol Sci., 28;22(21), 11652. doi: 10.3390/ijms222111652.

[18].  Alaskhar A. B., Khalaila, R., Wolf, J., von Bülow V., Harb, H., Alhamdan, F., Hii, C. S., Prescott, S. L., Ferrante, A., Renz, H., Garn, H., Potaczek, D. P., 2018, Histone modifications and their role in epigenetics of atopy and allergic diseases, Allergy Asthma Clin Immunol., 23(14), 39. doi: 10.1186/s13223-018-0259-4.

[19].  Kourtidou, C., Tziomalos, K., 2023, The Role of Histone Modifications in the Pathogenesis of Diabetic Kidney Disease. Int. J. Mol. Sci, 24, 6007, https://doi.org/10.3390/ijms24066007

[20].  Lu, H. C., Dai, W. N., He, L. Y., 2021, Epigenetic Histone Modifications in the Pathogenesis of Diabetic Kidney Disease. Diabetes Metab Syndr Obes, 14, 329-344 https://doi.org/10.2147/DMSO.S288500

[21].  O’Brien, J., Hayder, H., Zayed, Y., Peng, C., 2018, Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne), 9, 402. doi: 10.3389/fendo.2018.00402.

[22].  Wightman, B., Ha, I., Ruvkun, G., 1993, Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell, 75, 855–62. doi: 10.1016/0092-8674(93)90530-4

[23].  Lee, R. C., Feinbaum, R. L., Ambros, V., 1993, The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75, 843–54. doi: 10.1016/0092-8674(93)90529-Y.

[24].  Jo, S., Chen, J., Xu, G., Grayson, T. B., Thielen, L. A., Shalev, A., 2018, miR-204 Controls Glucagon-Like Peptide 1 Receptor Expression and Agonist Function. Diabetes, 67(2), 256–264. doi: 10.2337/db17-0506.

[25].  Bartel, D. P., Metazoan MicroRNAs, 2018, Cell, 173(1), 20–51. doi: 10.1016/j.cell.2018.03.006.

[26].  Denli, A. M., Tops, B. B., Plasterk, R. H., KettingM R. F., Hannon, G. J., 2004, Processing of primary microRNAs by the Microprocessor complex, Nature, 432, 231–5. doi: 10.1038/nature03049.

[27].  Yoda, M., Kawamata, T., Paroo, Z., Ye, X., Iwasaki, S., Liu, Q., et al. 2010, ATP-dependent human RISC assembly pathways, Nat Struct Mol Biol, 17, 17–23. doi: 10.1038/nsmb.1733

[28].  Vargas, E., Podder, V., Carrillo Sepulveda, M. A., Physiology, Glucose Transporter Type 4. 2023, In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.

[29].  Ramalingam, K., Yadalam, P. K., Ramani, P., Krishna, M., Hafedh, S., Badnjević, A., Cervino, G., & Minervini, G., 2024, Light gradient boosting-based prediction of quality of life among oral cancer-treated patients. BMC Oral Health, 24(1), 349. https://doi.org/10.1186/s12903-024-04050-x

[30].  Sagar, S., Ramani, P., Moses, S., Gheena, S. and Selvaraj, J., 2024, Correlation of salivary cytokine IL-17A and 1, 25 dihydroxycholecalciferol in patients undergoing orthodontic treatment. Odontology, pp.1-10.

[31].  Neralla, M. M. H., Preethi, A., Selvakumar, S. C., & Sekar, D., 2024, Expression levels of microRNA-7110 in oral squamous cell carcinoma. Minerva Dental and Oral Science, 73(3), 155–160. https://doi.org/10.23736/S2724-6329.23.04801-5

[32].  Erik A. R., 2021, Is GLUT4 translocation the answer to exercise-stimulated muscle glucose uptake? American Journal of Physiology-Endocrinology and Metabolism, 320(2), E240–E243.

[33].  Kaimala, S, Kumar, C. A., Allouh, M. Z., Ansari, S. A., Emerald, B. S., 2022, Epigenetic modifications in pancreas development, diabetes, and therapeutics. Med Res Rev, 42(3), 1343–1371. doi: 10.1002/med.21878.

[34].  Ramsundar, K., Jain, R. K., Balakrishnan, N., & Vikramsimha, B., 2023, Comparative evaluation of bracket bond failure rates of a novel non-primer adhesive with a conventional primer-based orthodontic adhesive - a pilot study. Journal of Dental Research, Dental Clinics, Dental Prospects, 17(1), 35–39. https://doi.org/10.34172/joddd.2023.36953.

[35].  Andersen, M. K., Pedersen, C. E., Moltke, I., Hansen, T., Albrechtsen, A., Grarup, N., 2016, Genetics of Type 2 Diabetes: The Power of Isolated Populations, Curr. Diab. Rep, 16, 65.

[36].  Cole, J. B., Florez, J. C., 2020, Genetics of diabetes mellitus and diabetes complications, Nat. Rev. Nephrol., 16, 377–390.

[37].  Udler, M. S., McCarthy, M. I., Florez, J. C., Mahajan, A., 2019, Genetic Risk Scores for Diabetes Diagnosis and Precision Medicine, Endocrine Rev, 40, 1500–1520.

[38].  Mahajan, A., Taliun, D., Thurner, M., Robertson, N. R., Torres, J. M., Rayner, N. W., Payne, A. J., Steinthorsdottir, V., Scott, R. A., Grarup, N.; et al., 2018, Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps, Nat. Genet, 50, 1505–1513.

[39].  Fathima, J. S., Jayaraman, S., Sekar, R. and Syed, N. H., 2024, The role of MicroRNAs in the diagnosis and treatment of oral premalignant disorders. Odontology, pp.1-10.

[40].  Florez, J. C., Udler, M. S., Hanson, R. L., Genetics of Type 2 Diabetes, 2018, In Diabetes in America, 3rd ed.; Cowie, C.C., Casagrande, S.S., Menke, A., Cissell, M.A., Eberhardt, M.S., Meigs, J.B., Gregg, E.W., Knowler, W.C., Barrett-Connor, E., Becker, D.J., et al., Eds.; National Institute of Diabetes and Digestive and Kidney Diseases (US): Bethesda, MA, USA, pp. 1–25, Chapter 14.

[41].  Florez, J. C., 2008, Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: Where are the insulin resistance genes? Diabetologia, 51, 1100–1110.

[42].  McCarthy, M. I., 2010, Genomics, type 2 diabetes, and obesity. N. Engl. J. Med, 363, 2339–2350.

[43].  Petrie, J. R., Pearson, E. R., Sutherland, C., 2011, Implications of genome wide association studies for the understanding of type 2 diabetes pathophysiology. Biochem. Pharmacol, 81, 471–477.

[44].  Altshuler, D., Hirschhorn, J. N., Klannemark, M., Lindgren, C. M., Vohl, M. C., Nemesh, J., Lane, C.R., Schaffner, S. F., Bolk, S., Brewer, C., et al., 2000, The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat. Genet., 26, 76–80.

[45].  Gloyn, A. L., Weedon, M. N., Owen, K. R., Turner, M. J., Knight, B. A., Hitman, G., Walker, M., Levy, J. C., Sampson, M., Halford, S., et al. 2003, Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes, Diabetes, 52, 568–572.

[46].  Chi, T., Lin, J., Wang, M., Zhao, Y., Liao, Z., Wei, P., 2021, Non-Coding RNA as Biomarkers for Type 2 Diabetes Development and Clinical Management. Front Endocrinol (Lausanne). 12:630032. doi: 10.3389/fendo.2021.630032.

[47].  Fanucchi, S., Domínguez-Andrés, J., Joosten, L. A. B., Netea, M. G., Mhlanga, M. M., 2021, The Intersection of Epigenetics and Metabolism in Trained Immunity. Immunity, 54(1), 32–43. doi: 10.1016/j.immuni.2020.10.011.

[48].  Krishnan, R. P., Pandiar, D., Ramani, P. and Jayaraman, S., 2025, Molecular profiling of oral epithelial dysplasia and oral squamous cell carcinoma using next generation sequencing. Journal of Stomatology, Oral and Maxillofacial Surgery, 126(4), p.102120.

[49].  Čugalj, K. B., Trebušak, K., Kovač, J., Šket, R., Jenko, B. B., Tesovnik, T., Debeljak, M., Battelino, T., Bratina, N., 2022, The Role of Epigenetic Modifications in Late Complications in Type 1 Diabetes. Genes (Basel), 13(4), 705. doi: 10.3390/genes13040705.

[50].  Singh, R., Chandel, S., Dey, D., Ghosh, A., Roy, S., Ravichandiran, V., Ghosh, D., 2020, Epigenetic modification and therapeutic targets of diabetes mellitus. Biosci Rep. 40(9): BSR20202160. doi: 10.1042/BSR20202160.

[51].  Paneni, F., Costantino, S., Battista, R., Castello, L., Capretti, G., Chiandotto, S., Scavone, G., Villano, A., Pitocco, D., Lanza, G., Volpe, M., Lüscher, T. F., Cosentino, F., 2015, Adverse epigenetic signatures by histone methyltransferase Set7 contribute to vascular dysfunction in patients with type 2 diabetes mellitus. Circ Cardiovasc Genet. 8(1):150-8. doi: 10.1161/CIRCGENETICS.114.000671.

[52].  Yasothkumar, D., Ramani, P., Jayaraman, S., Ramalingam, K., and Tilakaratne, W. M., 2024, Expression Profile of Circulating Exosomal microRNAs in Leukoplakia, Oral Submucous Fibrosis, and Combined Lesions of Leukoplakia and Oral Submucous Fibrosis. Head and Neck Pathology, 18(1), p.28.