The expression of fibrogenesis genes in tissues of patients with carotid atherosclerosis
https://doi.org/10.25557/2073-7998.2023.01.47-50
Abstract
We performed a whole-genome comparative analysis of gene expression in tissues of patients with carotid artery atherosclerosis using HumanHT-12_V4 BeadChip (Illumina, USA) microarray. We compared the expression between cells of the carotid artery in the area of atherosclerotic plaques (CAP, n = 3) and intact internal mammary arteries (IMA, n = 2). The targeted expression assessment was performed for ADAMDEC1, ITGB5, TIMP2, and ММР3 genes in blood leukocytes of patients (n = 21). A significant increase in expression of extracellular matrix organization genes (CD44, COL1A2, COL3A1, COL5A2, FMOD, HAPLN1, ITGA11, ITGAV, SPARC, SPP1, SULF1, TIMP1; |FC|≥2; pFDR = 1,44×10-7) was detected in CAP. The ADAMDEC1, ITGB5, and TIMP2 genes, are characterized by increased expression in CAP, compared with IMA (рFDR=0.018; рFDR = 0.011; рFDR=0.006, respectively). The ADAMDEC1, ITGB5, and TIMP2 genes are also expressed in peripheral blood leukocytes of patients; the highest level of expression is shown for the TIMP2 gene. Assessment of the expression level changes depending on genotypes showed that carriers of the TT genotype of rs1007856 in the ITGB5 gene have the lowest level of gene expression compared to carriers of the CC and CT genotypes (p = 0.034). Thus, carotid atherosclerosis is associated with an increase in the functional activity of fibrogenesis genes in vessels and blood leukocytes. The rs1007856 polymorphism is an eQTL for the ITGB5 gene in patients’ blood leukocytes.
Supporting agencies: The work was carried out according to the State Order of the Ministry of Science and Higher Education No. 122020300041-7
About the Authors
I. A. Goncharova
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
634050
10, Nab. r. Ushaiki
Tomsk
A. A. Sleptcov
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
634050
10, Nab. r. Ushaiki
Tomsk
I. A. Koroleva
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
634050
10, Nab. r. Ushaiki
Tomsk
M. S. Nazarenko
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
634050
10, Nab. r. Ushaiki
Tomsk
References
1. Palm F., Pussinen P. J., Safer A. et al. Serum matrix metalloproteinase-8, tissue inhibitor of metalloproteinase and myeloperoxidase in ischemic stroke. Atherosclerosis. 2018; 271: 9-14. doi: 10.1016/j.atherosclerosis.2018.02.012.
2. Taylor S. C., Laperriere G., Germain H. Droplet Digital PCR versus qPCR for gene expression analysis with low abundant targets: from variable nonsense to publication quality data. Sci Rep. 2017; 7 (1): 2409. doi: 10.1038/s41598-017-02217-x.
3. Goncharova I. A., Nazarenko M. S., Babushkina N. P., et al. Geneticheskaya predraspolozhennost’ k infarktu miokarda v raznykh vozrastnykh gruppakh [Genetic predisposition to an early myocardial infarction]. Molekulyarnaya biologiya [Molecular biology]. 2020; 54 (2): 224-232. doi: 10.31857/S0026898420020044. (In Russ.)
4. Goncharova I. A., Pecherina T. B., Markov A. V., et al. Rol’ genov fibrogeneza v formirovanii podverzhennosti k koronarnomu aterosklerozu [Fibrogenesis Genes and Susceptibility to Coronary Atherosclerosis]. Kardiologiia [Cardiology]. 2018; 58 (8): 33-44. (In Russ.) doi: 10.18087/cardio.2018.8.10160
5. Goncharova I. A., Pecherina T. B., Markov A. V., et al. Vklad genov fibrogeneza v izmenchivost’ ekhokardiograficheskikh parametrov miokarda u bol’nykh ibs v zavisimosti ot tyazhesti techeniya zabolevaniya. V sbornike: Genetika cheloveka i patologiya. Sbornik nauchnykh trudov. Vypusk 11. Pod redaktsiyey V. A. Stepanova [The contribution of fibrogenesis genes to the variability of echocardiographic parameters of the myocardium in patients with coronary heart disease depending on the severity of the course of the disease. In: Human genetics and pathology. Issue 11. Ed. by V.A. Stepanov]. 2017: 77-78. (In Russ.)
6. Goncharova I. A., Makeeva O. A., Golubenko M. V., et al. Geny fibrogeneza v determinatsii predraspolozhennosti k infarktu miokarda [Genes for fibrogenesis in the determination of susceptibility to myocardial infarction]. Molekulyarnaya biologiya [Molecular biology]. 2016; 50 (1): 94-105. doi: 10.7868/S0026898415060099. (In Russ.)
7. Bysani M., Agren R., Davegårdh C. et al. ATAC-seq reveals alterations in open chromatin in Pancreatic Islets from subjects with type 2 diabetes // Sci Rep. – 2019. – Vol. 9 (1): 7785.
8. Koliadenko V., Wilanowski T. Additional functions of selected proteins involved in DNA repair. Free Radic. Biol. Med. 2020; 146:1-15. doi: 10.1016/j.freeradbiomed.2019.10.010.
9. Xia Q., Zhang J., Han Y. et al. Epigenetic regulation of regulatory T cells in patients with abdominal aortic aneurysm. FEBS Open Bio. 2019; 9 (6): 1137-1143.
Review
For citations:
Goncharova I.A., Sleptcov A.A., Koroleva I.A., Nazarenko M.S. The expression of fibrogenesis genes in tissues of patients with carotid atherosclerosis. Medical Genetics. 2023;22(1):47-50. (In Russ.) https://doi.org/10.25557/2073-7998.2023.01.47-50
Views:
231
Email this article 