Effect of The Duration of The Diagnosis on DNA Methylation Changes in Three Different Diabetic Genes in Type 2 Diabetes Mellitus

https://doi.org/10.24017/science.2024.2.7

Abstract views: 0 / PDF downloads: 0

Authors

Abstract

The primary epigenetic alteration is DNA methylation. This study examined variations in DNA methylation in patients with type 2 diabetes at various time intervals, concentrating on the  Calpain-10 (CAPN10), ATP binding cassette subfamily C member 8 (ABCC8), and  Transcription factor 7-like 2 (TCF7L2) genes. Since persistent diabetes can lead to aberrant methylation patterns, it is interested in how long these changes may last. The blood samples from 140 individuals with Type 2 Diabetes Mellitus (T2DM) were collected, and the patients were grouped according to how long they had been diagnosed. Four groups of individuals were created based on their time on the disease: those with T2DM <1 year, those with T2DM 1-3 years, and those with T2DM 3-5 years.  The genders and ages of the participants were also noted. Using the Promega technique, bisulfite conversion and DNA extraction were completed. Methylation-specific PCR amplification was used to detect DNA methylation. In the study, ROC curve analysis, Chi-square and Spearman's correlation coefficients, as well as non-parametric tests, were employed to analyze the methylation percentage variation and methylation patterns among groups. A significant threshold of p < 0.05 was established. The results of the study indicated that the DNA methylation rates of T2DM patients and the control group differed significantly.  Patients with type 2 diabetes, particularly those who had just received a diagnosis, showed higher levels of methylation than the control group. The study also found that the length of diagnosis may have an impact on the discriminative strength of the DNA methylation status of the ABCC8 gene, resulting in varying degrees of T2DM prediction. 

Keywords:

DNA methylation, type 2 diabetes, methylation-specific PCR, bisulfite conversion and diag-nosis times

References

C. M. Lanata, S. A. Chung, and L. A. Criswell, “DNA methylation 101: what is important to know about DNA methylation and its role in SLE risk and disease heterogeneity,” Lupus Sci. Med., vol. 5, no. 1, Jul. 2018, doi: 10.1136/lupus-2018-000285. DOI: https://doi.org/10.1136/lupus-2018-000285

O. Ali, “Genetics of type 2 diabetes,” World J. Diabetes, vol. 4, no. 4, p. 114, Aug. 2013. doi: 10.4239/wjd.v4.i4.114. DOI: https://doi.org/10.4239/wjd.v4.i4.114

J. Robitaille and A. M. Grant, “The genetics of gestational diabetes mellitus: evidence for relationship with type 2 diabetes mellitus,” Genet. Med., vol. 10, no. 4, pp. 240–250, Apr. 2008, doi: 10.1097/gim.0b013e31816b8710. DOI: https://doi.org/10.1097/GIM.0b013e31816b8710

G. A. Raciti et al., “DNA Methylation and Type 2 Diabetes: Novel Biomarkers for Risk Assessment?,” Int. J. Mol. Sci., vol. 22, no. 21, p. 11652, Jan. 2021, doi: 10.3390/ijms222111652. DOI: https://doi.org/10.3390/ijms222111652

F. Alam, A. Islam, S. H. Gan, M. Mohamed, and T. H. Sasongko, "DNA methylation: an epigenetic insight into type 2 diabetes mellitus," Curr. Pharm. Des., vol. 22, no. 28, pp. 4398–4419, Aug. 2016. doi: 10.2174/1381612822666160527111152. DOI: https://doi.org/10.2174/1381612822666160527111152

S. A. H. Ahmed, S. A. Ansari, E. P. K. Mensah-Brown, and B. S. Emerald, “The role of DNA methylation in the pathogenesis of type 2 diabetes mellitus,” Clin. Epigenetics, vol. 12, no. 1, Jul. 2020, doi: 10.1186/s13148-020-00896-4. DOI: https://doi.org/10.1186/s13148-020-00896-4

A. Bansal and S. E. Pinney, "DNA methylation and its role in the pathogenesis of diabetes," Pediatr. Diabetes, vol. 18, no. 3, pp. 167–177, May 2017. doi: 10.1111/pedi.12521. DOI: https://doi.org/10.1111/pedi.12521

M. Kim, "DNA methylation: a cause and consequence of type 2 diabetes," Genomics Inform., vol. 17, no. 4, Dec. 2019. doi: 10.5808/GI.2019.17.4.e38. DOI: https://doi.org/10.5808/GI.2019.17.4.e38

N. Nadiger, J. K. Veed, P. C. Nataraj, and A. Mukhopadhyay, "DNA methylation and type 2 diabetes: a systemat-ic review," Clin. Epigenetics, vol. 16, no. 1, p. 67, May 2024. doi: 10.1186/s13148-024-01670-6 DOI: https://doi.org/10.1186/s13148-024-01670-6

E. Walaszczyk et al., “DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1c levels: a systematic review and replication in a case–control sample of the Lifelines study,” Diabetologia, vol. 61, no. 2, pp. 354–368, Nov. 2017, doi: https://doi.org/10.1007/s00125-017-4497-7. DOI: https://doi.org/10.1007/s00125-017-4497-7

Z. Maghbooli, B. Larijani, S. Emamgholipour, M. Amini, A. Keshtkar, and P. Pasalar, “Aberrant DNA methylation patterns in diabetic nephropathy,” J. Diabetes Metab. Disord., vol. 13, no. 1, Jun. 2014, doi: 10.1186/2251-6581-13-69. DOI: https://doi.org/10.1186/2251-6581-13-69

I. Khurana, H. Kaipananickal, S. Maxwell, S. Birkelund, A. Syreeni, C. Forsblom, J. Okabe, M. Ziemann, A. Kaspi, H. Rafehi, and A. Jørgensen, "Reduced methylation correlates with diabetic nephropathy risk in type 1 diabetes," J. Clin. Invest., vol. 133, no. 4, Feb. 2023. doi: 10.1172/JCI160959. DOI: https://doi.org/10.1172/JCI160959

H. Seo, J.-H. Park, J.-T. Hwang, H.-K. Choi, S.-H. Park, and J. Lee, “Epigenetic Profiling of Type 2 Diabetes Melli-tus: An Epigenome-Wide Association Study of DNA Methylation in the Korean Genome and Epidemiology Study,” genes, vol. 14, no. 12, pp. 2207–2207, Dec. 2023, doi: 10.3390/genes14122207. DOI: https://doi.org/10.3390/genes14122207

C. Sapienza, J. Lee, J. Powell, O. Erinle, F. Yafai, J. Reichert, E. S. Siraj, M. Madaio, "DNA methylation profiling identifies epigenetic differences between diabetes patients with ESRD and diabetes patients without nephropathy," Epigenetics, vol. 6, no. 1, pp. 20–28, Jan. 2011.doi: 10.4161/epi.6.1.13362. DOI: https://doi.org/10.4161/epi.6.1.13362

H. O. Smail and D. A. Mohamad, “Identification DNA Methylation Change of ABCC8 Gene in Type 2 Diabetes Mellitus as Predictive Biomarkers,” Aro J., vol. 10, no. 1, pp. 63–67, May 2022, doi: 10.14500/aro.10947. DOI: https://doi.org/10.14500/aro.10947

H. O. Smail and D. A. Mohamad, “Identification of DNA methylation change in TCF7L2 gene in the blood of type 2 diabetes mellitus as a predictive biomarker in Iraq Kurdistan region by using methylation-specific PCR,” Endocr. Regul., vol. 57, no. 1, pp. 53–60, Jan. 2023, doi: 10.2478/enr-2023-0007. DOI: https://doi.org/10.2478/enr-2023-0007

H. O. Smail and D. A. Mohamad, “Identification of DNA methylation of CAPN10 gene changes in the patients with type 2 diabetes mellitus as a predictive biomarker instead of HbA1c, random blood sugar, lipid profile, kid-ney function test, and some risk factors,” Endocr. Regul., vol. 57, no. 1, pp. 221–234, Jan. 2023, doi: 10.2478/enr-2023-0025. DOI: https://doi.org/10.2478/enr-2023-0025

P. Y. Lee, J. Costumbrado, C.-Y. Hsu, and Y. H. Kim, “Agarose Gel Electrophoresis for the Separation of DNA Fragments,” J. Vis. Exp., vol. 3923, no. 62, Apr. 2012, doi: 10.3791/3923. DOI: https://doi.org/10.3791/3923-v

GraphPad Software, LLC, “GraphPad Prism 8 User Guide - Welcome to Prism 8 User Guide,” Graphpad.com, 2015. https://www.graphpad.com/guides/prism/8/user-guide/index.htm

Y. Cheng et al., “Development and validation of DNA methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes,” Nat. Aging, pp. 1–9, Apr. 2023, doi: 10.1038/s43587-023-00391-4. DOI: https://doi.org/10.1038/s43587-023-00391-4

E. Aref-Eshghi, S. Biswas, C. Chen, B. Sadikovic, and S. Chakrabarti, “Glucose-induced, duration-dependent ge-nome-wide DNA methylation changes in human endothelial cells,” Am. J. Physiol. Cell Physiol., vol. 319, no. 2, pp. C268–C276, Aug. 2020, doi: 10.1152/ajpcell.00011.2020. DOI: https://doi.org/10.1152/ajpcell.00011.2020

T. C. Ong, S. D. Schibeci, N. L. Fewings, D. R. Booth, and G. P. Parnell, “Age-dependent VDR peak DNA methyl-ation as a mechanism for latitude-dependent multiple sclerosis risk,” Epigenetics Chromatin, vol. 14, no. 1, Feb. 2021, doi: 10.1186/s13072-021-00383-x. DOI: https://doi.org/10.1186/s13072-021-00383-x

M. J. Morris and L. M. Monteggia, "Role of DNA methylation and the DNA methyltransferases in learning and memory," Dialogues Clin. Neurosci., vol. 16, no. 3, pp. 359–371, Sep. 2014. doi: 10.31887/DCNS.2014.16.3/mmorris. DOI: https://doi.org/10.31887/DCNS.2014.16.3/mmorris

I. S. Kiselev, O. G. Kulakova, A. N. Boyko, and O. O. Favorova, “DNA Methylation As an Epigenetic Mechanism in the Development of Multiple Sclerosis,” Acta Naturae, vol. 13, no. 2, pp. 45–57, Jul. 2021, doi: 10.32607/actanaturae.11043. DOI: https://doi.org/10.32607/actanaturae.11043

R. G. Miller, J. C. Mychaleckyj, Suna Onengut-Gumuscu, T. J. Orchard, and T. Costacou, “TXNIPDNA methyla-tion is associated with glycemic control over 28 years in type 1 diabetes: findings from the Pittsburgh Epidemiolo-gy of Diabetes Complications (EDC) study,” BMJ Open Diabetes Res. Care, vol. 11, no. 1, pp. e003068–e003068, Jan. 2023, doi: 10.1136/bmjdrc-2022-003068. DOI: https://doi.org/10.1136/bmjdrc-2022-003068

C. Davegårdh, S. García-Calzón, K. Bacos, and C. Ling, “DNA methylation in the pathogenesis of type 2 diabetes in humans,” Mol. Metab., vol. 14, pp. 12–25, Aug. 2018, doi: 10.1016/j.molmet.2018.01.022. DOI: https://doi.org/10.1016/j.molmet.2018.01.022

C. Ling and T. Rönn, "Epigenetics in human obesity and type 2 diabetes," Cell Metab., vol. 29, no. 5, pp. 1028–1044, May 2019. doi: 10.1016/j.cmet.2019.03.009. DOI: https://doi.org/10.1016/j.cmet.2019.03.009

C. F. Silvia, “The association of DNA methylation patterns in TCF7L2 and GIPR genes with Type 2 Diabetes,” Handle.net, Nov. 2014. https://diposit.ub.edu/dspace/bitstream/2445/60043/1/SCF_THESIS.pdf

M. Zhu et al., “Site-specific DNA methylation in KCNJ11 promoter contributes to type 2 diabetes,” Medrxiv. Jul. 2024, doi: 10.1101/2024.07.13.24310360. DOI: https://doi.org/10.2139/ssrn.4898588

M. Cappetta, L. Fernandez, L. Brignoni, N. Artagaveytia, C. Bonilla, M. López, M. Esteller, B. Bertoni, and M. Ber-dasco, "Discovery of novel DNA methylation biomarkers for non‐invasive sporadic breast cancer detection in the Latino population," Mol. Oncol., vol. 15, no. 2, pp. 473–486, Feb. 2021. doi: 10.1002/1878-0261.12842. DOI: https://doi.org/10.1002/1878-0261.12842

A. Khamis et al., “Epigenetic changes associated with hyperglycaemia exposure in the longitudinal D.E.S.I.R. co-hort,” Diabetes Metab., vol. 48, no. 4, p. 101347, Jul. 2022, doi: 10.1016/j.diabet.2022.101347. DOI: https://doi.org/10.1016/j.diabet.2022.101347

T. Dayeh et al., “DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk,” Epigenetics, vol. 11, no. 7, pp. 482–488, Jun. 2016, doi: 10.1080/15592294.2016.1178418. DOI: https://doi.org/10.1080/15592294.2016.1178418

Downloads

How to Cite

[1]
H. O. Smail, “Effect of The Duration of The Diagnosis on DNA Methylation Changes in Three Different Diabetic Genes in Type 2 Diabetes Mellitus”, KJAR, vol. 9, no. 2, pp. 86–95, Nov. 2024, doi: 10.24017/science.2024.2.7.

Article Metrics

Published

25-11-2024

Issue

Section

Pure and Applied Science