RGD Reference Report - Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease. - Rat Genome Database

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Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease.

Authors: Lamblin, N  Bauters, C  Hermant, X  Lablanche, JM  Helbecque, N  Amouyel, P 
Citation: Lamblin N, etal., J Am Coll Cardiol. 2002 Jul 3;40(1):43-8.
RGD ID: 1582363
Pubmed: PMID:12103254   (View Abstract at PubMed)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MMP12Humancoronary aneurysm susceptibilityIAGP  RGD 
Mmp12Ratcoronary aneurysm susceptibilityISOMMP12 (Homo sapiens) RGD 
Mmp12Mousecoronary aneurysm susceptibilityISOMMP12 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp12  (matrix metallopeptidase 12)

Genes (Mus musculus)
Mmp12  (matrix metallopeptidase 12)

Genes (Homo sapiens)
MMP12  (matrix metallopeptidase 12)


Additional Information