Stromelysin-1 (MMP-3) gene 5A/6A promoter polymorphism is associated with blood pressure in a community population.

Background And Objectives: Arterial remodelling contributes to the development of hypertension. Stromelysin-1 (MMP-3), a member of the matrix metalloproteinase family may contribute to this process. Stromelysin-1 gene expression is partly regulated by a common polymorphism in the promoter region of either five or six consecutive adenosine bases (5A/6A).

Methods And Results: A cross-sectional study of 1111 randomly selected male and female community subjects (27-77 years), were assessed for conventional cardiovascular risk factors and stromelysin-1 5A-1171-6A genotype. Multivariate analysis showed an independent association between the stromelysin-1 genotype and blood pressure that was recessive for the 5A/5A genotype. Subjects with the 5A/5A genotype had a higher mean systolic blood pressure (SBP) (+4.2 mmHg) and diastolic blood pressure (DBP) (+2.2 mmHg) compared to subjects with 5A/6A and 6A/6A genotypes. Subgroup analysis revealed an independent association of the 5A/5A genotype with SBP (+3.6 mmHg, P = 0.001) and DBP (+2.0 mmHg, P = 0.004) in subjects not on blood pressure medication. Whereas subjects with the 5A/5A genotype and taking medication had a higher mean SBP (+7.4 mmHg, P = 0.02) and DBP (+2.7 mmHg, P = 0.11). Multivariate analysis in the whole population showed there was no association between genotypes and mean intimal-medial wall thickness (IMT) (P = 0.87) or the likelihood of carotid plaque formation.

Conclusions: The stromelysin-1 5A-1171-6A genotype is an important determinant of blood pressure in this general population sample.