Jguirim-Souissi Imen, Jelassi Awatef, Slimani Afef, Addad Faouzi, Hassine Majed, Hamda Khaldoun Ben, Najah Mohamed, Maatouk Faouzi, Rouis Mustapha, Slimane Mohamed Naceur
Unit of Research, Genetic and Biologic Factors of Atherosclerosis, Faculty of Medicine, Monastir, Tunisia.
Coron Artery Dis. 2011;22(6):388-93. doi: 10.1097/MCA.0b013e3283478d40.
In this study, we investigated the association between matrix metalloproteinase-1 (MMP-1) G-1607GG, MMP-12 A-82G and MMP-12 A1082G genotypes and haplotypes and the prognosis of coronary artery disease (CAD).
A total of 129 Tunisian patients with CAD were followed prospectively for a median of 2.5 years. Genotypes were determined by a PCR-based restriction fragment length polymorphism. Two endpoints were considered: restenosis and incidence of clinical vascular events (restenosis, myocardial infarction, stroke, cardiac death).
Genotypes of MMP-1 G-1607GG, MMP-12 A-82G and MMP-12 A1082G were not associated with the incidence of restenosis or clinical events. Analysis of haplotypes consisting of alleles of MMP-1 G-1607GG and MMP-12 A1082G showed that the rate of clinical events was significantly higher in patients carrying the GG-A haplotype than those with other haplotypes (0.637 vs. 0.424, respectively, odds ratio=1.45; 95% confidence interval=1.04-2.04; P<0.05; P adjusted for multiple risk factors). However, after Bonferroni correction for multiple comparisons, this difference did not reach statistical significance (P=0.093), showing that there was a tendency for the association between the GG-A haplotype and future clinical events in patients with CAD.
These findings showed a trend of the GG-A haplotype of MMP-1 G-1607GG/MMP-12 A1082G towards the prediction of future clinical events in patients with CAD and suggested a possible importance of these loci in the prediction of the prognosis of CAD. Studies with large sample size are warranted to better investigate this association, as MMP genotyping could aid in identifying patients who are likely to have unfavourable prognosis.
在本研究中，我们调查了基质金属蛋白酶-1（MMP-1）G-1607GG、MMP-12 A-82G和MMP-12 A1082G基因及单倍型与冠状动脉疾病（CAD）预后之间的关联。
对129例突尼斯CAD患者进行了前瞻性随访，中位随访时间为2.5年。通过基于聚合酶链反应的限制性片段长度多态性确定基因型。考虑了两个终点：再狭窄和临床血管事件（再狭窄、心肌梗死、中风、心源性死亡）的发生率。
MMP-1 G-1607GG、MMP-12 A-82G和MMP-12 A1082G的基因型与再狭窄或临床事件的发生率无关。对由MMP-1 G-1607GG和MMP-12 A1082G等位基因组成的单倍型分析显示，携带GG-A单倍型的患者临床事件发生率显著高于携带其他单倍型的患者（分别为0.637和0.424，比值比=1.45；95%置信区间=1.04-2.04；P<0.05；针对多个风险因素进行校正后的P值）。然而，在进行Bonferroni多重比较校正后，这种差异未达到统计学显著性（P=0.093），表明CAD患者中GG-A单倍型与未来临床事件之间存在关联趋势。
这些发现显示了MMP-1 G-1607GG/MMP-12 A1082G的GG-A单倍型在预测CAD患者未来临床事件方面的趋势，并提示这些基因座在预测CAD预后方面可能具有重要意义。由于MMP基因分型有助于识别可能预后不良的患者，因此有必要进行大样本研究以更好地调查这种关联。
