Methylation levels in the 5' region of the TBX20 gene in the ascending aorta change in opposite direction in atherosclerosis and aneurysm

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Аннотация

We found hypomethylation of 5 CpG sites in the 5’region of TBX20 gene (7p14.2) in the tissues of atherosclerotic aortic plaque compared to dilated part of aorta in patients with ascending aortic aneurysm. Using GEO database, we found that the DNA methylation level in the chr7:35253926-35262250 region changes in opposite direction in aortic dissection and aortic atherosclerosis. The results suggest an alteration in epigenetic regulation both in aortic atherosclerosis andaortic aneurysm.

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Yu. Koroleva

Tomsk National Research Medical Center, Russian Academy of Sciences

Хат алмасуға жауапты Автор.
Email: yuliya.koroleva@medgenetics.ru

Research Institute of Medical Genetics

Ресей, 634050, Tomsk

I. Goncharova

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: yuliya.koroleva@medgenetics.ru

Research Institute of Medical Genetics

Ресей, 634050, Tomsk

A. Zarubin

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: yuliya.koroleva@medgenetics.ru

Research Institute of Medical Genetics

Ресей, 634050, Tomsk

S. Shipulina

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: yuliya.koroleva@medgenetics.ru

Research Institute of Medical Genetics

Ресей, 634050, Tomsk

A. Sleptsov

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: yuliya.koroleva@medgenetics.ru

Research Institute of Medical Genetics

Ресей, 634050, Tomsk

D. Panfilov

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: yuliya.koroleva@medgenetics.ru

Research Institute of Cardiology

Ресей, 634012, Tomsk

В. Kozlov

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: yuliya.koroleva@medgenetics.ru

Research Institute of Cardiology

Ресей, 634012, Tomsk

M. Nazarenko

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: yuliya.koroleva@medgenetics.ru

Research Institute of Medical Genetics

Ресей, 634050, Tomsk

Әдебиет тізімі

  1. Portelli S.S., Robertson E.N., Malecki C. et al. Epigenetic influences on genetically triggered thoracic aortic aneurysm // Biophys. Rev. 2018. V. 10. № 5. P. 1241–1256. https://doi.org/10.1007/s12551-018-0460-1
  2. Liu P., Zhang J., Du D. et al. Altered DNA methylation pattern reveals epigenetic regulation of Hox genes in thoracic aortic dissection and serves as a biomarker in disease diagnosis // Clin. Epigenetics. 2021. V. 13. № 1. P. 124. https://doi.org/10.1186/s13148-021-01110-9
  3. Leone O., Corsini A., Pacini D. et al. The complex interplay among atherosclerosis, inflammation, and degeneration in ascending thoracic aortic aneurysms // J. Thorac. Cardiovasc. Surg. 2020. V. 160. № 62. P. 1434–1443. https://doi.org/10.1016/j.jtcvs.2019.08.108
  4. Isselbacher E.M., Preventza O., H. Black J. 3rd. et al. ACC/AHA guideline for the diagnosis and management of aortic disease: A report of the American Heart Association // Circulation. 2022. V. 146. № 24. P. e334– e482. https://doi.org/10.1161/CIR.0000000000001106
  5. Chau K.H., Bender J.R., Elefteriades J.A. Silver lining in the dark cloud of aneurysm disease // Cardiology. 2014. V. 128. № 4. P. 327–332. https://doi.org/10.1159/000358123
  6. Weininger G., Ostberg N., Shang M. et al. Lipid profiles help to explain protection from systemic atherosclerosis in patients with ascending aortic aneurysm // J. Thorac. Cardiovasc. Surg. 2022. V. 163. № 2. P. e129–e132. https://doi.org/10.1016/j.jtcvs.2021.09.031
  7. Nassar L.R., Barber G.P., Benet-Pagès A. et al. The UCSC Genome Browser database: 2023 update // Nucl. Ac. Res. 2023. V. 51. № D1. P. D1188–D1195. https://doi.org/10.1093/nar/gkac1072
  8. Barrett T., Wilhite S.E., Ledoux P. et al. NCBI GEO: archive for functional genomics data sets--update // Nucl. Ac. Res. 2013. V. 41. P. D991–D995. https://doi.org/10.1093/nar/gkac1072
  9. Chen Y., Xiao D., Zhang L. et al. The role of Tbx20 in cardiovascular development and function // Front. Cell Dev. Biol. 2021. V. 9. https://doi.org/10.3389/fcell.2021.638542
  10. Kirk E.P., Sunde M., Costa M.W. et al. Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy // Am. J. Hum. Genet. 2007. V. 81. № 2. P. 280–291. https://doi.org/10.1086/519530
  11. Luyckx I., Kumar A.A., Reyniers E. et al. Copy number variation analysis in bicuspid aortic valve-related aortopathy identifies TBX20 as a contributing gene // Eur. J. Hum. Genet. 2019. V. 27. № 7. P. 1033–1043. https://doi.org/10.1038/s41431-019-0364-y
  12. Tcheandjieu C., Xiao K., Tejeda H. et al. High heritability of ascending aortic diameter and trans-ancestry prediction of thoracic aortic disease // Nat. Genet. 2022. V. 54. № 6. P. 772–782. https://doi.org/10.1038/s41588-022-01070-7
  13. Sollis E., Mosaku A., Abid A. et al. The NHGRI-EBI GWAS Catalog: Knowledgebase and deposition resource // Nucl. Ac. Res. 2023. V. 51. № D1. P. D977–D985. https://doi.org/10.1093/nar/gkac1010
  14. Li Y., Ren P., Dawson A. et al. Single-cell transcriptome analysis reveals dynamic cell populations and differential gene expression patterns in control and aneurysma l human aortic tissue // Circulation. 2020. V. 142. № 14. P. 1374–1388. https://doi.org/10.1161/CIRCULATIONAHA.120.046528
  15. Ma W.F., Hodonsky C.J., Turner A.W. et al. Enhanced single-cell RNA-seq work-flow reveals coronary artery disease cellular cross-talk and candidate drug targets // Atherosclerosis. 2022. V. 340. P. 12–22. https://doi.org/10.1016/j.atherosclerosis.2021.11.025
  16. Hodonsky C.J., Turner A.W., Khan M.D. et al. Integrative multi-ancestry genetic analysis of gene regulation in coronary arteries prioritizes disease risk loci // medRxiv. 2023. V. 2. https://doi.org/10.1101/2023.02.09.23285622
  17. Lacey M., Baribault C., Ehrlich K.C., Ehrlich M. Atherosclerosis-associated differentially methylated regions can reflect the disease phenotype and are often at enhancers // Atherosclerosis. 2019. V. 280. P. 183–191. https://doi.org/10.1016/j.atherosclerosis.2018.11.031
  18. Yang X., Kong Q., Li Z. et al. Association between the promoter methylation of the TBX20 gene and tetralogy of fallot // Scand. Cardiovascular J. 2018 V. 52. № 5. P. 287–291. https://doi.org/10.1080/14017431.2018.1499955
  19. Gong J., Sheng W., Ma D. et al. DNA methylation status of TBX20 in patients with tetralogy of Fallot // BMC Med. Genomics. 2019. V. 12. № 1. P. 75. https://doi.org/10.1186/s12920-019-0534-3

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2. Fig. 1. Localization and epigenetic context of the studied 5' region of the TBX20 gene. Thin colored vertical lines mark five DMCs between the atherosclerotic plaque of the dilated part of the aorta not affected by atherosclerosis, the dilated part of the aorta and the non-dilated proximal part of the aorta (this study). Wide vertical stripes indicate: yellow – regions hypomethylated in myocardial tissues with tetrad Fallot [18, 19], blue – regions hypomethylated in aortic tissues with atherosclerosis [17]. The differences in the level of methylation between the unaffected aortic tissues and the atherosclerotically altered aorta for the three regions (from left to right) were 41, 29 and 30%. Red horizontal lines indicate regions of hypermethylated CpG sites in aortic dissection (GSE84274 [8]), blue horizontal lines indicate regions of hypomethylated CpG sites in aortic atherosclerosis compared to unaffected aortic tissue (GSE46394 [8]). All tracks are received and/or aligned on UCSC GenomeBrowser (GRCh38 genome assembly).

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