TGFB1 rs1800470 Polymorphism is Associated with Circulating TGF-β1 Levels and Left Ventricular Geometry in Hypertensive Patients
Abstract
BACKGROUND: Transforming growth factor β1 (TGF-β1) is a major mediator of myocardial fibrosis and cardiac remodeling in hypertension. TGFB1 (rs1800470) and MTHFR (rs1801133) are known for their roles in TGF-β1 regulation and cardiovascular remodeling, with MTHFR rs1801133 potentially influencing TGF-β1–mediated fibrosis through homocysteine metabolism. However, genetic determinants and relationship of these polymorphism with left ventricular (LV) structure remain unclear in the Indonesian population. Clarifying these associations may improve risk stratification and precision care. Therefore, this study was conducted to assess the associations of these polymorphisms and TGF-β1 levels with LV remodeling in essential hypertension.
METHODS: Sixty-four adults subjects with essential hypertension were included in this cross-sectional study, and their blood samples were taken. Genotyping of the MTHFR and TGFB1 genes was performed using polymerase chain reaction (PCR), followed by sequencing. Serum TGF-β1 was measured by enzyme-linked immunosorbent assay (ELISA), while LV mass index (LVMI) and relative wall thickness (RWT) were assessed by echocardiography.
RESULTS: TGFB1 rs1800470 was significantly associated with higher TGF-β1 levels (p=0.013). In the recessive model, TT homozygotes had higher TGF-β1 than CC+CT carriers (β=1.444; standardized β=0.353; p=0.004). TGF-β1 correlated with LDL cholesterol and diastolic blood pressure (r=0.302; p=0.015 and r=0.277; p=0.027). The TT genotype was associated with higher RWT under recessive and overdominant models (p=0.021 and p=0.028).
CONCLUSION: TGFB1 rs1800470 is associated with circulating TGF-β1 concentrations in essential hypertension, suggesting a potential role in hypertensive cardiac remodeling.
KEYWORDS: hypertension, TGFB1 polymorphism, TGF-β1, cardiac remodeling, left ventricular geometry, myocardial fibrosis
References
Zhou B, Carrillo-Larco RM, Danaei G, Riley LM, Paciorek CJ, Stevens GA, et al. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: A pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021; 398(10304): 957-80, CrossRef.
Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, et al. Heart disease and stroke statistics-2023 update: A report from the American Heart Association. Circulation. 2023; 147(8): e93-e621, CrossRef.
Kawasoe S, Ohishi M. Regression of left ventricular hypertrophy. Hypertens Res. 2024; 47(5): 1225-6, CrossRef.
Díez J, González A, Kovacic JC. Myocardial interstitial fibrosis in nonischemic heart disease, part 3/4: JACC Focus Seminar. J Am Coll Cardiol. 2020; 75(17): 2204-18, CrossRef.
Frangogiannis NG. Transforming growth factor-β in tissue fibrosis. J Exp Med. 2020; 217(3): e20190103, CrossRef.
Chen F, Lyu L, Xing C, Chen Y, Hu S, Wang M, et al. The pivotal role of TGF-β/Smad pathway in fibrosis pathogenesis and treatment. Front Oncol. 2025; 15: 1649179, CrossRef.
Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC. Cardiac fibrosis: The fibroblast awakens. Circ Res. 2016; 118(6): 1021-40, CrossRef.
Györfi AH, Matei A-E, Distler JHW. Targeting TGF-β signaling for the treatment of fibrosis. Matrix Biol. 2018; 68-69: 8-27, CrossRef.
Ramos-Mondragón R, Galindo CA, Avila G. Role of TGF-beta on cardiac structural and electrical remodeling. Vasc Health Risk Manag. 2008; 4(6): 1289-300, CrossRef.
Lu Y, Boer JMA, Barsova RM, Favorova O, Goel A, Müller M, et al. TGFB1 genetic polymorphisms and coronary heart disease risk: A meta-analysis. BMC Med Genet. 2012; 13: 39, CrossRef.
Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, et al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet. 1999; 8(1): 93-7, CrossRef.
Deng Y, Li Z, An X, Fan R, Wang Y, Li J, et al. Hyperhomocysteinemia Promotes Cardiac Hypertrophy in Hypertension. Oxid Med Cell Longev. 2022; 2022: 1486157, CrossRef.
Shi Y, Zhao L, Zhang Y, Qin Q, Cong H, Guo Z. Homocysteine promotes cardiac fibrosis by regulating the Akt/FoxO3 pathway. Ann Transl Med. 2021; 9(23): 1732, CrossRef.
van Meurs JBJ, Pare G, Schwartz SM, Hazra A, Tanaka T, Vermeulen SH, et al. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease. Am J Clin Nutr. 2013; 98(3): 668-76, CrossRef.
Leopold JA, Loscalzo J. Emerging role of precision medicine in cardiovascular disease. Circ Res. 2018; 122(9): 1302-15, CrossRef.
Scaglione R, Argano C, Duro G, Di Chiara T, Nuzzo D, Colomba D, et al. The relationship between the transforming growth factor β 1 T29C gene polymorphism and left ventricular geometry and function in hypertensive subjects. Int J Hypertens. 2010; 2010: 647147, CrossRef.
Xu J, Yu X, Huang C, Qin R, Peng F, Lin J, et al. Association of 5 well-defined polymorphisms in the gene encoding transforming growth factor-β1 with coronary artery disease among Chinese patients with hypertension. Angiology. 2015; 66(7): 652-8, CrossRef.
McCarthy CP, Bruno RM, McEvoy JW, Touyz RM. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension: what is new in pharmacotherapy? Eur Heart J Cardiovasc Pharmacother. 2025; 11(1): 7-9, CrossRef.
Mitchell C, Rahko PS, Blauwet LA, Canaday B, Finstuen JA, Foster MC, et al. Guidelines for performing a comprehensive transthoracic echocardiographic examination in adults: Recommendations from the American Society of Echocardiography. J Am Soc Echocardiogr. 2019; 32(1): 1-64, CrossRef.
Li A, Huang W, Yang Q, Peng L, Liu Q. Expression of the C677T polymorphism of the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene in patients with carotid artery atherosclerosis. Med Sci Monit. 2020: 26: e920320, CrossRef.
Ishibashi CM, Oliveira CEC de, Guembarovski RL, Banin-Hirata BK, Vitiello GAF, Guembarovski AL, et al. Genetic polymorphisms of the TGFB1 signal peptide and promoter region: Role in wilms tumor ssceptibility? J Kidney Cancer VHL. 2021; 8(4): 22-31, CrossRef.
Lucas JA, Zhang Y, Li P, Gong K, Miller AP, Hassan E, et al. Inhibition of transforming growth factor-signaling induces left ventricular dilation and dysfunction in the pressure-overloaded heart. Am J Physiol Heart Circ Physiol. 2010; 298(2): 424-32, CrossRef.
Ser ÖS, Çetinkal G, Kiliçarslan O, Dalgıç Y, Batit S, Keskin K, et al. The comparison of serum TGF-beta levels and associated polymorphisms in patients with coronary artery ectasia and normal coronary artery. Egypt Heart J. 2021; 73(1): 32, CrossRef.
Pratiwi D, Rizqiana M, Wicaksono A, Permatasari D, Restuti RD, Susilawati TN, et al. TNF-α and TGF-β contributes in recurrent otorrhea of active mucosal chronic otitis media. Indones Biomed J. 2022; 14(1): 59-65, CrossRef.
Kamoun M. Cellular and molecular parameters in human renal allograft rejection. Clin Biochem. 2001; 34(1): 29-34, CrossRef.
Stadtlober NP, Flauzino T, Santos LF da RF, Iriyoda TMV, Costa NT, Lozovoy MAB, et al. TGFB1 +869 T > C (rs1800470) variant is independently associated with susceptibility, laboratory activity, and TGF-β1 in patients with systemic lupus erythematosus. Autoimmunity 2021; 54(8): 569-75, CrossRef.
National Center for Biotechnology Information (NCBI) [Internet]. Reference SNP (rs) Report: rs1800470 [cited 2026 Jan 3; updated 2024 Sep 3]. Available from: https://www.ncbi.nlm.nih.gov/.
Ensembl [Internet]. rs1800470 SNP Population genetics [cited 2026 Jan 3; updated 2025 Sep] Available from: https://www.ensembl.org/.
Kurabekova RM, Gichkun OE, Tsirulnikova OM, Pashkova IE, Fomina VA, Shevchenko OP, et al. Analysis of the association between the TGFb1 gene haplotype and liver diseases in children. Acta Naturae. 2023; 15(3): 75-81, CrossRef.
Steed MM, Tyagi SC. Mechanisms of cardiovascular remodeling in hyperhomocysteinemia. Antioxid Redox Signal. 2011; 15(7): 1927-43, CrossRef.
Gong K, Chen YF, Li P, Lucas JA, Hage FG, Yang Q, et al. Transforming growth factor-β inhibits myocardial PPARγ expression in pressure overload-induced cardiac fibrosis and remodeling in mice. J Hypertens. 2011; 29(9): 1810-9, CrossRef.
Wijaya J, Donosepoetro M, Bakri S. The different concentrations of transforming growth factor-beta1 (TGF-beta1), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor receptor-2 (VEGFR-2) in normoalbuminuria normotension, normoalbuminuria hypertension. Indones Biomed J. 2009; 1(3): 65-70, CrossRef.
Gichkun OE, Shevchenko OP, Kurabekova RM, Mozheiko NP, Shevchenko AO. The rs1800470 polymorphism of the TGFB1 gene is associated with myocardial fibrosis in heart transplant Recipients. Acta Naturae. 2021; 13(4): 42-6, CrossRef.
Supriono, Nugraheni A, Kalim H, Eko MH. The effect of curcumin on regression of liver fibrosis through decreased expression of transforming growth factor-β1 (TGF-β1). Indones Biomed J. 2019; 11(1): 52-8, CrossRef.
Ahmed SN, Jhaj R, Sadasivam B, Joshi R. Regression of the Left Ventricular Hypertrophy in Patients with Essential Hypertension on Standard Drug Therapy. Discoveries. 2020; 8(3): e115, CrossRef.
Puntmann VO, Peker E, Chandrashekhar Y, Nagel E. T1 mapping in characterizing myocardial disease. Circ Res. 2016; 119(2): 277-99, CrossRef.
Chu HW, Hwang IC, Kim HM, Park J, Choi H, Choi H-M, et al. Age-dependent implications of left ventricular hypertrophy regression in patients with hypertension. Hypertens Res. 2024; 47(5): 1144-56, CrossRef.
Zhang ZY, Thijs L, Staessen JA. Left ventricular mass in relation to midlife blood pressure. Eur. Heart J. 2014; 35(46): 3242-4, CrossRef.
Samii A, Aslani S, Imani D, Razi B, Samaneh Tabaee S, Jamialahmadi T, et al. MTHFR gene polymorphisms and susceptibility to myocardial infarction: Evidence from meta-analysis and trial sequential analysis. Int J Cardiol Heart Vasc. 2023; 49: 101293, CrossRef.
Liu X, Luo F, Li J, Wu W, Li L, Chen H. Homocysteine induces connective tissue growth factor expression in vascular smooth muscle cells. J Thromb Haemost. 2008; 6(1): 184-92, CrossRef.
DOI: https://doi.org/10.18585/inabj.v18i3.4105
Copyright (c) 2026 The Prodia Education and Research Institute
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:
The Prodia Education and Research Institute
