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

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 (nZ217, mean age 46 +/- 1 years). Supine blood pressure, carotidefemoral pulse wave velocity (PWV) and augmentation index (AIx) were assessed. Results: Blood pressure and aorticPWV 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 -1562Tor836A alleles had significantly higher blood pressure and PWV compared with haplotypes that contained neither allele (p < 0.0001). These polymorphismswere 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 (r(2) = 0.45, p < 0.0001). Conclusions: Aortic PWV and blood pressure were modulated by -1562C > Tand -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. (C) 2009 Association for Research into Arterial Structure and Physiology. Published by Elsevier B.V. All rights reserved.