P.061 A Haplotype at the MMP-9 Locus is Associated with Higher Blood Pressure and Greater Arterial Stiffness in Patients with Essential Hypertension

Abstract

Arterial stiffness is the result of a complex interplay between gene and environment. The metalloproteniases (MMPs) play an important role in vascular remodelling and plasma MMP-9 levels predict cardiovascular disease.We studied the effect of two MMP-9 polymorphisms ; -1562C>T and -836G>A on blood pressure (BP) and arterial stiffness in essential hypertension.

We measured BP, pulse wave velocity (PWV) and augmentation index (AIx) in 217 untreated hypertensive patients (mean age 46 ± 1 years (108 male). MMP-9 polymorphisms were screened using RFLP. Haplotypes were determined using HAP analysis. Results analysed with JMP Version 5.0 and expressed as Mean ± SEM, p<0.05 considered significant.

Aortic PWV and BP were significantly higher in –1563T (TT homozygotes and CT heterozygotes) and 836 A allele carriers (AA homozygotes and GA heterozygotes). The predicted haplotypes were independently associated with aortic PWV and BP with a significant gene dose effect. In stepwise regression analysis, the –1562T and 836A alleles were independent determinants of PWV, in addition to age and BP. These polymorphisms were also independent determinants of both systolic and diastolic BP, either individually or when included together in the model.

Variation in the MMP-9 gene may modulate BP and aortic stiffness probably through accelerated turnover of vascular extracellular matrix. The significant gene-dose effect suggests that even one copy of the rare allele (A & T) may increase the risk of arterial stiffness and higher BP.A future challenge would be to use genotyping to identify high-risk individuals and to tailor anti-hypertensive treatment for achieving optimum BP control and reduced arterial stiffness.