K. Shioji, Y. Kokubo, Y. Goto
Mar 1, 2004
Citations
1
Influential Citations
12
Citations
Quality indicators
Journal
Journal of Thrombosis and Haemostasis
Abstract
Matrix metalloproteinases (MMPs), enzymes that degrade extracellular matrix, have been extensively found in human coronary atherosclerotic plaques, which suggests that MMPs play an important role in plaque instability [1]. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in regulating the plasma homocysteine level, and hyperhomocysteinemia confers an increased risk of coronary artery disease [2]. Polymorphisms of stromelysin-1 (MMP3) and MTHFR have been reported to be related to an increased risk of myocardial infarction (MI), but the results have been controversial [3–7]. To assess whether these polymorphisms are associated with the incidence of MI, we conducted an association study. The study population consisted of two groups: (i) 1857 (849 male and 1008 female) controls consecutively recruited from the Suita Study between April 2002 and February 2003 [8,9], and (ii) 548 (474 male and 74 female) patients with MI recruited from the National Cardiovascular Center between May 2001 and April 2003 [10]. The MMP3 5A/6A and MTHFR C677T polymorphisms were determined by the TaqMan system (the primer and probe sequences are available on request). Univariate analysis showed that MMP3 5A/6A was not associated with the incidence of MI (Table 1). Logistic analysis indicated that the 5A/5A+5A/6A genotype of MMP3 only tended to be more susceptible to MI than the 6A/6A genotype [P 1⁄4 0.1004, odds ratio (OR) 1⁄4 1.23, 95% confidence interval (CI) 0.96, 1.59] in male subjects. MTHFR C677T was not associated with the incidence of MI (Table 1). Logistic analysis indicated that the CC genotype of MTHFR only tended to be more susceptible to MI than the CT+TT genotype (P 1⁄4 0.0911, OR 1⁄4 1.52, 95% CI 0.93, 2.48) in female subjects. None of the genotypes significantly influenced the secondary incidence of acute coronary syndrome (Kaplan–Meier method). Moreover, none of the genotypes significantly influenced the severity of coronary atherosclerosis as assessed by the number of stenotic lesions (>75%) by coronary arteriography. No significant deviation from Hardy–Weinberg equilibrium was observed for MMP3 5A/6A or MTHFR C677T. It has been reported that individuals carrying the 6A/6A genotype of MMP3 are predisposed to developing atherosclerotic plaques with significant stenosis, whereas those carrying the 5A allele are predisposed to developing unstable plaque [4]. In the Japanese population, MMP-3 5A/6A was initially