Artery Research

Volume 3, Issue 1, February 2009, Pages 17 - 23

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

Authors
Azra Mahmuda, b, *, Sixiang Zhoua, Anthony W. Ryanc, Paula Jerrard-Dunnea, b, John Feelya, b
aDepartment of Pharmacology and Therapeutics, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin 8, Ireland
bHypertension Clinic, St. James’s Hospital, Dublin 8, Ireland
cDepartment of Clinical Medicine and Institute of Molecular Medicine, St. James’s Hospital, Dublin 8, Ireland
*Corresponding author. Department of Pharmacology and Therapeutics, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin 8, Ireland. Tel.: +35318961563; fax: +35314539033. E-mail address: mahmuda@tcd.ie (A. Mahmud).
Corresponding Author
Azra Mahmud
Received 24 July 2007, Revised 20 October 2008, Accepted 7 January 2009, Available Online 8 February 2009.
DOI
10.1016/j.artres.2009.01.002How to use a DOI?
Keywords
MMP-9; Polymorphism; Haplotype; Arterial stiffness; Aortic pulse wave velocity; Hypertension; Augmentation index
Abstract

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 T allele 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 −1562T or 836A alleles 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.

Copyright
© 2009 Association for Research into Arterial Structure and Physiology. Published by Elsevier B.V. All rights reserved.
Open Access
This is an open access article distributed under the CC BY-NC license.

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Journal
Artery Research
Volume-Issue
3 - 1
Pages
17 - 23
Publication Date
2009/02/08
ISSN (Online)
1876-4401
ISSN (Print)
1872-9312
DOI
10.1016/j.artres.2009.01.002How to use a DOI?
Copyright
© 2009 Association for Research into Arterial Structure and Physiology. Published by Elsevier B.V. All rights reserved.
Open Access
This is an open access article distributed under the CC BY-NC license.

Cite this article

TY  - JOUR
AU  - Azra Mahmud
AU  - Sixiang Zhou
AU  - Anthony W. Ryan
AU  - Paula Jerrard-Dunne
AU  - John Feely
PY  - 2009
DA  - 2009/02/08
TI  - A haplotype at the MMP-9 locus is associated with high-blood pressure and arterial stiffness in patients with essential hypertension
JO  - Artery Research
SP  - 17
EP  - 23
VL  - 3
IS  - 1
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2009.01.002
DO  - 10.1016/j.artres.2009.01.002
ID  - Mahmud2009
ER  -