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Published Online First: 11 August 2006. doi:10.1136/jmg.2006.040808
Journal of Medical Genetics 2006;43:897-901
Copyright © 2006 by the BMJ Publishing Group Ltd.

REVIEW

The role of genetic variants of matrix metalloproteinases in coronary and carotid atherosclerosis

Sonia Abilleira, Steve Bevan, Hugh S Markus

Department of Clinical Neuroscience, St George’s University of London, London, UK

Correspondence to:
S Abilleira
Agència d’Avaluació de Tecnologia i Recerca Mèdiques (AATRM), Parc Sanitari Pere Virgili, C/Esteve Terrades 30, Edifici Tramuntana, 2a planta, Barcelona 08023, Spain; sabilleira{at}aatrm.catsalut.net

Current evidence suggests that matrix metalloproteinases (MMPs) have a role in early atherosclerosis, plaque rupture and myocardial infarction. Polymorphisms in MMP genes have been examined for associations with atherosclerosis, but interpretation is complicated by methodological issues. This article presents a systematic review of these association studies and a meta-analysis of available data for polymorphisms where a sufficient number of studies was available. The 5A allele of the MMP3 5A/6A polymorphism was associated with acute myocardial infarction (odds ratio (OR) 1.26, 95% confidence interval (CI) 1.1 to 1.4, p<0.001), suggesting its role in plaque rupture. There was no association with the functional MMP9 –1562C/T polymorphism (OR 1.11, 95% CI 1.0 to 1.3, p = 0.18). Current data provide evidence for the role of MMP3 polymorphism in plaque destabilisation, but elucidation of the role of other MMP gene variants in atherosclerosis will depend on better study design, including a larger sample size, extensive screening of individual genes with haplotype analysis and replication of studies to avoid publication bias.

Abbreviations: CAD, coronary artery disease; IMT, intima–media thickness; MMP, matrix metalloproteinase


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