CLINICAL STUDY
Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease
Nicolas Lamblin, MD* ,
Christophe Bauters, MD, FACC*,*,
Xavier Hermant,
Jean-Marc Lablanche, MD, FACC*,
Nicole Helbecque, PhD and
Philippe Amouyel, MD, PhD*
* Centre Hospitalier Universitaire de LilleLille Cedex, France
INSERM U508, Institut Pasteur de Lille, Lille Cedex, France
Manuscript received January 10, 2002;
revised manuscript received March 6, 2002,
accepted March 14, 2002.
* Reprint requests and correspondence: Dr. Christophe Bauters, Service de Cardiologie C, Hôpital Cardiologique, CHRU de Lille, 59037 Lille Cedex, France.
cbauters{at}chru-lille.fr
OBJECTIVES: Our hypothesis was that functional polymorphisms in matrix metalloproteinase (MMP) genes may act as susceptibility factors for the development of coronary aneurysms (CAs).
BACKGROUND: Different forms of remodeling have been described at the level of coronary arteries; CA, reported in 1% to 5% of patients with angiographic evidence of coronary artery disease (CAD), are one of them. Matrix metalloproteinases have been implicated in the pathogenesis of aneurysm development through increased proteolysis of extracellular matrix proteins.
METHODS: We screened 3,862 patients who underwent coronary angiography and identified 113 patients with CAD with at least one CA (CA group); these patients were matched with 226 patients with CAD without CA (control group). The –1,306 C/T MMP-2, 5A/6A MMP-3, CA-repeat MMP-9 and –82 A/G MMP-12 polymorphisms were determined.
RESULTS: The MMP-2, MMP-9 and MMP-12 polymorphisms were not associated with CA. By contrast, the 5A/5A genotype of MMP-3 was significantly more frequent in the CA group than in the control group (31% vs. 18%, p = 0.015); similarly, the MMP-3 5A allele was more frequent in the CA group (p = 0.009). Three variables were independently associated with CA: the MMP-3 5A/5A genotype (odds ratio [OR] = 2.23, 95% confidence interval [CI] [1.27 to 3.93]), a previous myocardial infarction (OR = 1.91, 95% CI [1.14 to 3.20]) and a history of aortic aneurysm (OR = 21.06, 95% CI [2.35 to 188]).
CONCLUSIONS: The MMP-3 5A allele is associated with the occurrence of CA. Our results suggest that an increased proteolysis in the arterial wall may act as a susceptibility factor for the development of CA in patients with coronary atherosclerosis.
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Abbreviations and Acronyms
| | CA | | coronary aneurysm | | CAD | | coronary artery disease | | CI | | confidence interval | | MI | | myocardial infarction | | MMP | | matrix metalloproteinase | | OR | | odds ratio | | PCR | | polymerase chain reaction | | TIMP | | tissue inhibitor of metalloproteinases |
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