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

Azra Mahmud; Sixiang Zhou; Anthony W. Ryan; Paula Jerrard-Dunne; John Feely

doi:10.1016/j.artres.2009.01.002

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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 Mahmud^a^{, b}^{, *}, Sixiang Zhou^a, Anthony W. Ryan^c, Paula Jerrard-Dunne^a^{, b}, John Feely^a^{, 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.2009.01.002 How 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.
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.2009.01.002 How to use a DOI?
Open Access: This is an open access article distributed under the CC BY-NC license.

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ris enw bib

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  -

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