Combined Effect Of COL1A1 And EDN1 Gene Polymorphisms On The Risk Of Developing Cardiological Complications

Zokirova Muborakkhon Bobir kizi

doi:10.37547/ijmsphr/Volume07Issue01-06

Authors

Zokirova Muborakkhon Bobir kizi

Republican Scientific and Practical Medical Center of Hematology, Tashkent State Medical University, Uzbekistan

Keywords

COL1A1 EDN1 gene polymorphism

Abstract

Background: Cardiological complications are a leading cause of adverse outcomes in patients with systemic diseases. Genetic factors, particularly those influencing myocardial structure and vascular regulation, play a significant role in individual susceptibility. Polymorphisms in the COL1A1 gene are associated with myocardial fibrosis and remodeling, while variations in the EDN1 gene are linked to endothelial dysfunction and vasoconstriction. However, the combined effect of these polymorphisms on cardiovascular risk remains underexplored.

Objective: To assess the association of COL1A1 and EDN1 gene polymorphisms with the risk of developing cardiological complications and to evaluate their combined effect on structural and vascular abnormalities.

Materials and Methods: An observational case-control study included 199 participants: 102 patients with an underlying disease (subdivided into 64 with and 38 without cardiological complications) and 97 healthy controls. Cardiological complications were diagnosed based on clinical, ECG, echocardiographic, and laboratory criteria. Genotyping of COL1A1 and EDN1 polymorphisms was performed using PCR. Statistical analysis included allele frequency comparison, odds ratios (OR), and risk stratification.

Results: Carriers of the minor A allele of COL1A1 and the Asn allele of EDN1 showed a trend toward increased risk of complications (OR=1.22, 95% CI: 0.67–2.22 and OR=1.36, 95% CI: 0.70–2.64, respectively). Combined carriage of both unfavorable alleles was associated with a higher frequency of complications and demonstrated an additive risk increase compared to isolated variants.

Conclusion: Polymorphisms in COL1A1 and EDN1 are associated with an elevated risk of cardiological complications, with combined carriage resulting in additive risk. These findings support an integrated genetic approach to cardiovascular risk prediction and may inform personalized prevention strategies.

Downloads

Download data is not yet available.

References

1

Sayed, N., Aboelnaga, S., & El-Sherbiny, M. (2019). Genetic factors influencing cardiovascular disease risk: An updated review. Cardiovascular Research, 115(10), 1502–1515. https://doi.org/10.1093/cvr/cvz030

2

Khera, A. V., & Kathiresan, S. (2020). Genetics of coronary artery disease: Discovery, biology and clinical translation. Nature Reviews Genetics, 21(10), 589–602. https://doi.org/10.1038/s41576-020-0237-8

3

Torkamani, A., Wineinger, N. E., & Topol, E. J. (2018). The personal and clinical utility of polygenic risk scores. Nature Reviews Genetics, 19(9), 581–590. https://doi.org/10.1038/s41576-018-0018-x

4

Travers, J. G., Kamal, F. A., Robbins, J., Yutzey, K. E., & Blaxall, B. C. (2016). Cardiac fibrosis: The fibroblast awakens. Circulation Research, 118(6), 1021–1040. https://doi.org/10.1161/CIRCRESAHA.115.306565

5

Frangogiannis, N. G. (2019). The extracellular matrix in myocardial injury, repair, and remodeling. Journal of Clinical Investigation, 129(8), 3300–3312. https://doi.org/10.1172/JCI120394

6

Kong, P., Christia, P., & Frangogiannis, N. G. (2020). The pathogenesis of cardiac fibrosis. Cellular and Molecular Life Sciences, 77(4), 523–540. https://doi.org/10.1007/s00018-019-03291-7

7

Zhao, M., Li, Y., Wang, H., & Zhang, X. (2019). COL1A1 polymorphisms and cardiovascular disease risk: A systematic review. Molecular Genetics & Genomic Medicine, 7(9), e00812. https://doi.org/10.1002/mgg3.812

8

Wang, Q., Xu, H., Li, Z., & Chen, J. (2021). Association of COL1A1 gene variants with myocardial fibrosis and cardiovascular outcomes. BMC Cardiovascular Disorders, 21, 405. https://doi.org/10.1186/s12872-021-02194-3

9

Li, Y., Zhang, J., & Gao, W. (2022). Functional implications of COL1A1 polymorphisms in cardiovascular remodeling. Frontiers in Cardiovascular Medicine, 9, 850123. https://doi.org/10.3389/fcvm.2022.850123

10

Barton, M., & Yanagisawa, M. (2019). Endothelin: 30 years from discovery to therapy. Hypertension, 74(6), 1232–1251. https://doi.org/10.1161/HYPERTENSIONAHA.119.13253

11

Dhaun, N., Goddard, J., & Webb, D. J. (2020). The endothelin system and its antagonism in cardiovascular disease. Journal of Cardiovascular Pharmacology, 76(3), 244–257. https://doi.org/10.1097/FJC.0000000000000824

12

Khimji, A. K., & Rockey, D. C. (2020). Endothelin biology and disease. Cellular Signalling, 73, 109694. https://doi.org/10.1016/j.cellsig.2020.109694

13

Gohar, A., Ali, M., & Hassan, A. (2021). EDN1 gene variants and cardiovascular risk: Evidence from clinical studies. Journal of Human Hypertension, 35, 587–596. https://doi.org/10.1038/s41371-020-00448-y

14

El-Gohary, Y., Mostafa, M., & Abdelrahman, M. (2023). EDN1 polymorphisms in ischemic heart disease: A systematic review. Cardiology Research and Practice, 2023, 9876543. https://doi.org/10.1155/2023/9876543

15

Ingelsson, E., & McCarthy, M. I. (2018). Human genetics of heart disease: Insights from genome-wide association studies. Current Opinion in Cardiology, 33(3), 268–276. https://doi.org/10.1097/HCO.0000000000000514

16

Arnett, D. K., Blumenthal, R. S., Albert, M. A., Buroker, A. B., Goldberger, Z. D., Hahn, E. J., ... & Ziaeian, B. (2019). 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease. Circulation, 140(11), e596–e646. https://doi.org/10.1161/CIR.0000000000000678

17

Libby, P., Luscher, T., & Ridker, P. M. (2021). Inflammation and cardiovascular disease: From pathophysiology to clinical practice. European Heart Journal, 42(43), 4503–4515. https://doi.org/10.1093/eurheartj/ehab756