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.
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.
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Authors: Jeffrey L Anderson; Benjamin D Horne; Nicola J Camp; Joseph B Muhlestein; Paul N Hopkins; Lisa A Cannon-Albright; Chrissa P Mower; James J Park; Jessica L Clarke; Zachary P Nicholas; Jason T McKinney; John F Carlquist Journal: Am Heart J Date: 2010-08 Impact factor: 4.749
Authors: Jaroslav Alois Hubacek; Vladimír Staněk; Marie Gebauerová; Alexandra Pilipčincová; Rudolf Poledne; Michal Aschermann; Hana Skalická; Jana Matoušková; Andreas Kruger; Martin Pěnička; Hana Hrabáková; Josef Veselka; Petr Hájek; Vera Lánská; Věra Adámková; Jan Pit'ha Journal: Exp Clin Cardiol Date: 2010