Abstract
BACKGROUND: The matrix metalloproteinase-2 (MMP2) rs243865 polymorphism has been associated with cardiovascular events; however, its impact on difficult-to-control hypertension remains unclear. This study aims to assess the characteristics of rs243865 polymorphism and its association with target organ damage in adult patients with difficult-to-control hypertension in Vietnam. METHODS: A cross-sectional study was conducted on 70 difficult-to-control hypertensive patients at two medical centers in Southern Vietnam. All patients underwent Sanger sequencing for analysis of the MMP2 rs243865 polymorphism. Target organ damage (TOD) was assessed across cardiac (left ventricular hypertrophy (LVH), myocardial ischemia), renal (decreased glomerular filtration rate, microalbuminuria), and vascular (carotid stenosis, peripheral vascular disease) systems, with patient-level counts of damaged target-organ systems derived. Data were processed in R 4.5.0 (RStudio, 2025), and associations were analyzed using logistic regression with false discovery rate (FDR) control based on Storey's q-values. RESULTS: Analysis of the MMP2 rs243865 polymorphism revealed a predominance of the C allele (87.1%), with the CC genotype being the most common (75.7%). Allele/genotype distributions did not differ across clinical features (p > 0.05) except for higher dyslipidemia in C-allele carriers and the CC genotype (p = 0.035 and p = 0.033). Adjusted models (age, sex, dyslipidemia, duration of hypertension, and duration of diabetes) showed the C allele and CC genotype associated with microalbuminuria (q = 0.041; q = 0.049), echocardiographic LVH (q = 0.039; q = 0.027), and renal TOD (q = 0.019; q = 0.027). CC genotype associations were observed for LVH on echocardiography (q = 0.027), combined LVH (q = 0.028) and cardiac TOD (q = 0.039), and lower odds of carotid artery stenosis (q = 0.039). The C allele was associated with ≥ 2 damaged organ systems (q = 0.026). CONCLUSION: Preliminary findings suggest a possible involvement of the MMP2 rs243865 polymorphism in target organ damage among patients with difficult-to-control hypertension.