Background: Resistant hypertension (RH) remains a major clinical challenge due to its strong association with cardiovascular complications and target organ damage (TOD). Matrix metalloproteinase-2 (MMP-2), an enzyme involved in extracellular matrix remodeling, has been implicated in vascular stiffness and cardiac remodeling. Genetic polymorphisms of MMP-2 may influence its activity and thereby affect TOD severity.

Objective: This study aimed to investigate the rs243865 (−1306C>T) polymorphism in the MMP-2 gene and its association with TOD among Vietnamese patients with RH.

Methods: A cross-sectional analytical study was conducted on 78 patients diagnosed with RH at Can Tho Central General Hospital and Can Tho University of Medicine and Pharmacy Hospital between July 2023 and February 2024. Clinical parameters, echocardiographic findings, carotid-femoral pulse wave velocity (cfPWV), and urinary albumin-to-creatinine ratio were assessed. Genotyping of rs243865 was performed using direct Sanger sequencing.

Results: The distribution of rs243865 genotypes was 77% CC, 21% CT, and 3% TT, with an allele T frequency of 23%. TOD was prevalent, with cfPWV >10 m/s in 79% of patients and microalbuminuria in 76%. The rs243865 T allele was significantly associated with reduced ejection fraction (OR 8.1, 95% CI 1.3–51.4; P = .03) and carotid artery stenosis (OR 4.5, 95% CI 1.1–20.1; P = .048). T allele carriers also exhibited higher arterial stiffness indices compared with CC carriers.

Conclusions: The rs243865 (−1306C>T) polymorphism in the MMP-2 gene may serve as a genetic determinant of cardiovascular and vascular damage in patients with RH. These findings underscore the importance of incorporating genetic profiling into personalized risk assessment and management strategies for hypertension-related TOD.

Dr. An Tuan Huynh is a medical doctor and lecturer at Can Tho University of Medicine and Pharmacy, Vietnam. His main research interests include resistant hypertension, cardiovascular genetics, and target organ damage. His current studies aim to elucidate how these functional variants of MMP-2 influence arterial stiffness, left ventricular hypertrophy, and renal impairment in patients with resistant hypertension. His recent article, “The rs243865 Polymorphism in Matrix Metalloproteinase-2 and its Association With Target Organ Damage in Patients With Resistant Hypertension: Cross-Sectional Study,” published in JMIR Cardio (2025), represents one of the first genetic studies of its kind in the Vietnamese population. He is actively involved in developing genetic-based risk prediction models and promoting personalized cardiovascular medicine in resource-limited settings, integrating clinical, echocardiographic, and molecular data to enhance early detection and prevention of hypertensive complications.