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A haplotype at the MMP-9 locus is associated with high-blood pressure and arterial stiffness in patients with essential hypertension

Artery Research volume 3, pages 17–23 (2009)Cite this article

Summary

Background

Arterial stiffness is an independent predictor of cardiovascular events in hypertensive populations and is in part a heritable trait. Matrix metalloproteinase (MMPs) plays an important role in vascular remolding. MMP-9 levels predict cardiovascular risk and are associated with aortic stiffness. We investigated the influence of two MMP-9 polymorphisms (-1562C > T, 836G > A) on arterial stiffness and blood pressure in hypertensive subjects.

Methods

MMP-9 genotypes and plasma MMP-9 concentrations were determined in untreated patients (n = 217, mean age 46 ± 1 years). Supine blood pressure, carotid—femoral pulse wave velocity (PWV) and augmentation index (AIx) were assessed.

Results

Blood pressure and aortic PWV were higher in Tallele carriers of the -1562C > T polymorphism and the A allele carriers of the 836G > A polymorphism. The two polymorphisms had a significant gene dose-dependent effect on PWV (p < 0.01). The -1562C/836A (AC) haplotype was the most frequent (58%). All haplotypes containing either-1562Tor836Aalleles had significantly higher blood pressure and PWV compared with haplotypes that contained neither allele (p < 0.0001). These polymorphisms were also associated with higher aortic PWV after correction for confounding variables. In stepwise regression models, genetic variants emerged as independent determinants of PWV in addition to age; mean arterial pressure and heart rate (r2 = 0.45, p < 0.0001).

Conclusions

Aortic PWV and blood pressure were modulated by -1562C > T and -836G > A polymorphisms in the MMP-9 gene in this treatment naive hypertensive population. These genetic polymorphisms may help to identify hypertensive patients at increased risk of cardiovascular events.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin 8, Ireland

    Azra Mahmud, Sixiang Zhou, Paula Jerrard-Dunne & John Feely

  2. Hypertension Clinic, St. James’s Hospital, Dublin 8, Ireland

    Azra Mahmud, Paula Jerrard-Dunne & John Feely

  3. Department of Clinical Medicine and Institute of Molecular Medicine, St. James’s Hospital, Dublin 8, Ireland

    Anthony W. Ryan

Authors
  1. Azra Mahmud
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  2. Sixiang Zhou
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  4. Paula Jerrard-Dunne
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Correspondence to Azra Mahmud.

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This is an open access article distributed under the CC BY-NC license. https://doi.org/creativecommons.org/licenses/by/4.0/

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Mahmud, A., Zhou, S., Ryan, A.W. et al. A haplotype at the MMP-9 locus is associated with high-blood pressure and arterial stiffness in patients with essential hypertension. Artery Res 3, 17–23 (2009). https://doi.org/10.1016/j.artres.2009.01.002

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  • DOI: https://doi.org/10.1016/j.artres.2009.01.002

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Artery Research

ISSN: 1876-4401

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