Association of MMP2 gene single nucleotide polymorphisms and serum matrix metalloproteinase-2 levels with hypertension-mediated target organ damage in patients with resistant hypertension
Main Article Content
Abstract
Resistant hypertension (RH) carries a high risk of hypertension-mediated organ damage (HMOD). This cross-sectional study enrolled 413 hypertensive patients (213 RH, 200 non-RH). Serum MMP-2 was measured by ELISA; three MMP2 single nucleotide polymorphisms (SNP1 rs243866, SNP2 rs243865, SNP3 rs2285053) were genotyped by Sanger sequencing/ASO-PCR. HMOD burden was higher in the RH group compared with the non-RH group. Serum MMP-2 did not differ between groups (p = 0.684), but within the RH group it was independently associated with decreased eGFR (β = −0.298, p = 0.010), elevated urinary ACR (β = +7.534, p = 0.009), and increased LAi (β = +0.046, p = 0.007) after multivariate adjustment. Under an additive model, the SNP1 A-allele was independently associated with EF < 50% (OR = 3.578, p = 0.006) and albuminuria (OR = 2.432, p = 0.013); the SNP3 T-allele was independently associated with left ventricular hypertrophy (OR = 1.621, p = 0.027). Circulating MMP-2 and MMP2 polymorphisms play complementary but distinct roles: MMP-2 reflects renal and left atrial damage, while genetic variants shape cardiac phenotypes, suggesting that integrating both layers of biological information may improve risk stratification in resistant hypertension.
Article Details
Keywords
Resistant hypertension, MMP-2, MMP2 gene polymorphisms, hypertension-mediated organ damage, rs243866, rs2285053
References
2. Carey RM, Calhoun DA, Bakris GL, et al. Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association. Hypertension. 2018; 72(5): e53-e90. doi:10.1161/HYP.0000000000000084.
3. Trần Kim Sơn, Lâm Thị Chư Láng, Nguyễn Quan Đức Minh. Tăng huyết áp kháng trị: Vai trò của cá thể hóa điều trị trong kỷ nguyên y học chính xác. Tạp chí Nghiên cứu Y học. 2025; 195(10): 168-174. doi:10.52852/tcncyh.v195i10.4080.
4. Muiesan ML, Salvetti M, Rizzoni D, et al. Resistant hypertension and target organ damage. Hypertens Res. 2013; 36(6): 485-491. doi:10.1038/hr.2013.30.
5. Prado AF, Batista RIM, Tanus-Santos JE, Gerlach RF. Matrix Metalloproteinases and Arterial Hypertension: Role of Oxidative Stress and Nitric Oxide in Vascular Functional and Structural Alterations. Biomolecules. 2021; 11(4): 585. Published 2021 Apr 16. doi:10.3390/biom11040585.
6. Baudier RL, Orlandi PF, Yang W, et al. Matrix Metalloproteinase-2 and CKD Progression: The Chronic Renal Insufficiency Cohort (CRIC) Study. Kidney Med. 2024; 6(8): 100850. Published 2024 Jun 6. doi:10.1016/j.xkme.2024.100850.
7. Ritter AMV, de Faria AP, Barbaro NR, et al. The rs243866/243865 polymorphisms in MMP-2 gene and the relationship with BP control in obese resistant hypertensive subjects. Gene. 2018; 646: 129-135. doi:10.1016/j.gene.2017.12.023.
8. Price SJ, Greaves DR, Watkins H. Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation. J Biol Chem. 2001; 276(10): 7549-7558. doi:10.1074/jbc.M010242200.
9. Sabbatini AR, Barbaro NR, de Faria AP, et al. Matrix metalloproteinase-2 -735C/T polymorphism is associated with resistant hypertension in a specialized outpatient clinic in Brazil. Gene. 2017; 620: 23-29. doi:10.1016/j.gene.2017.04.004.
10. Lacchini R, Jacob-Ferreira AL, Luizon MR, et al. Common matrix metalloproteinase 2 gene haplotypes may modulate left ventricular remodelling in hypertensive patients. J Hum Hypertens. 2012; 26(3): 171-177. doi:10.1038/jhh.2011.8.