# Matrix metalloproteinase-2 (MMP2) rs243865 polymorphism and target end-organ damage in difficult-to-control hypertensive patients

**Authors:** Thuc Tri Nguyen, An Viet Tran, An Tuan Huynh, Quyen Thuy Nguyen, Linh Giao Ly Pham, Bao The Nguyen

PMC · DOI: 10.7717/peerj.20489 · PeerJ · 2026-03-06

## TL;DR

This study explores how a genetic variation in the MMP2 gene may be linked to organ damage in patients with hard-to-control high blood pressure in Vietnam.

## Contribution

The study is the first to investigate the association between the MMP2 rs243865 polymorphism and target organ damage in difficult-to-control hypertensive patients in Vietnam.

## Key findings

- The C allele and CC genotype of MMP2 rs243865 were associated with kidney and heart damage in patients.
- The CC genotype was linked to lower odds of carotid artery stenosis and higher risk of left ventricular hypertrophy.
- C allele carriers were more likely to have damage in two or more organ systems.

## Abstract

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.

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.

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).

Preliminary findings suggest a possible involvement of the MMP2 rs243865 polymorphism in target organ damage among patients with difficult-to-control hypertension.

## Linked entities

- **Genes:** MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313]
- **Diseases:** myocardial ischemia (MONDO:0024644), carotid stenosis (MONDO:0001612), peripheral vascular disease (MONDO:0005294)

## Full-text entities

- **Genes:** MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** obesity (MESH:D009765), autoimmune diseases (MESH:D001327), stroke (MESH:D020521), overweight (MESH:D050177), proteinuria (MESH:D011507), ischemia (MESH:D007511), Carotid stenosis (MESH:D016893), Peripheral vascular disease (MESH:D016491), Disease (MESH:D004194), Dyslipidemia (MESH:D050171), myocardial remodeling (MESH:D064752), cancer (MESH:D009369), Diabetes (MESH:D003920), Chronic Kidney Disease (MESH:D051436), heart, kidney, and vascular injury (MESH:D007674), depression (MESH:D003866), dyskinesia (MESH:D004409), TOD (MESH:D000092124), TIA (MESH:D002546), type 2 diabetes (MESH:D003924), cardiac damage (MESH:D006331), dementia (MESH:D003704), akinesia (MESH:C537921), stage II (MESH:D062706), cardiac, renal, or vascular injury (MESH:D006322), sepsis (MESH:D018805), carotid atherosclerosis (MESH:D002340), cardio-renal complications (MESH:D059347), ventricular hypertrophy (MESH:D024741), hypokinesia (MESH:D018476), hypertensive (MESH:D006973), LVH (MESH:D017379), end-organ damage (MESH:C564816), Myocardial ischemia (MESH:D017202), cardiovascular dysfunction (MESH:D002318), arterial stenosis (MESH:D012078), renal involvement (MESH:C565423)
- **Chemicals:** H2O (MESH:D014867), Cholesterol (MESH:D002784), ethanol (MESH:D000431), DEPC (MESH:D004047), EDTA (MESH:D004492), aldosterone (MESH:D000450), agarose (MESH:D012685), lipid (MESH:D008055), creatinine (MESH:D003404), glucose (MESH:D005947), dNTPs (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** -1306 C>T, rs243866, M235T, rs676210, -735C/T, A1166C

## Full text

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## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12970309/full.md

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Source: https://tomesphere.com/paper/PMC12970309