Document Detail

Multiple-polymorphism associations of 7 matrix metalloproteinase and tissue inhibitor metalloproteinase genes with myocardial infarction and angiographic coronary artery disease.
MedLine Citation:
PMID:  17893005     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMP) genes may be associated with myocardial infarction (MI) and coronary artery disease (CAD), but studies of multiple MMP genes and their tissue inhibitors (TIMPs) are scarce. Furthermore, differentiation of predictive ability by end point (MI vs CAD) has not been addressed. This study evaluated the association with MI of SNPs in genes encoding MMPs 1, 2, 3, and 9 and TIMPs 1, 2, and 3.
METHODS: Genotypes of patients (N = 5148) with MI (n = 1693) and angiographically defined CAD (> or = 1 lesion of > or = 70% stenosis, n = 1967) were compared with MI-free (n = 3455) and non-CAD patients (n = 1122), respectively. Because of linkage disequilibrium, MMP-1 and MMP-3 SNPs (chromosome 11) were combined, as were the 2 MMP-9 SNPs.
RESULTS: For MI, only MMP-9 group CT/RQ (odds ratio [OR] 1.25, P = .007 vs wild-type CC/RR) had greater MI risk, with TT/QQ having a weak trend (OR 1.43, P = .10). These findings remained (CT/RQ) or were strengthened (TT/QQ) after full adjustment. For CAD, association was found for MMP-1/MMP-3 groups 2G1G/6A6A (OR 1.45, P = .022), 2G1G/6A5A (OR = 1.49, P = .001), 2G1G/5A5A (OR 1.64, P = .003), and 1G1G/5A5A (OR 1.35, P = .035) compared to wild type.
CONCLUSIONS: Composite MMP-9 genotypes but not other SNPs were associated with MI, whereas MMP-1/MMP-3 genotypes were CAD-associated. The largest MMP/TIMP gene study to date, this study suggests care in selection and definition of clinical phenotypes. Furthermore, this suggests that the evaluated SNPs only approximately account for intragenic variation in these genes and that comprehensive evaluation of all variations in these genes should better elucidate associations with MI and CAD phenotypes.
Benjamin D Horne; Nicola J Camp; John F Carlquist; Joseph B Muhlestein; Matthew J Kolek; Zachary P Nicholas; Jeffrey L Anderson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American heart journal     Volume:  154     ISSN:  1097-6744     ISO Abbreviation:  Am. Heart J.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-25     Completed Date:  2007-11-06     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  0370465     Medline TA:  Am Heart J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  751-8     Citation Subset:  AIM; IM    
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MeSH Terms
Coronary Angiography
Coronary Disease / genetics*,  physiopathology,  radiography
Diabetic Angiopathies / genetics
Matrix Metalloproteinase 1 / genetics
Matrix Metalloproteinase 2 / genetics
Matrix Metalloproteinase 3 / genetics
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinases / genetics*
Middle Aged
Myocardial Infarction / genetics*,  physiopathology
Polymorphism, Single Nucleotide
Tissue Inhibitor of Metalloproteinase-1 / genetics
Tissue Inhibitor of Metalloproteinase-2 / genetics
Tissue Inhibitor of Metalloproteinase-3 / genetics
Tissue Inhibitor of Metalloproteinases / genetics*
Grant Support
CA098364/CA/NCI NIH HHS; HL071878/HL/NHLBI NIH HHS; K07 CA098364/CA/NCI NIH HHS; K07 CA098364-01A1/CA/NCI NIH HHS; K07 CA098364-02/CA/NCI NIH HHS; K07 CA098364-03/CA/NCI NIH HHS; K07 CA098364-04/CA/NCI NIH HHS; K07 CA098364-05/CA/NCI NIH HHS; R01 HL071878-01A2/HL/NHLBI NIH HHS; R01 HL071878-02/HL/NHLBI NIH HHS; R01 HL071878-03/HL/NHLBI NIH HHS; R01 HL071878-04/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Tissue Inhibitor of Metalloproteinase-1; 0/Tissue Inhibitor of Metalloproteinase-3; 0/Tissue Inhibitor of Metalloproteinases; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC 3.4.24.-/Matrix Metalloproteinases; EC Metalloproteinase 3; EC protein, human; EC Metalloproteinase 2; EC Metalloproteinase 9; EC protein, human; EC Metalloproteinase 1

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