Pavkova Goldbergova Monika, Jarkovsky Jiri, Lipkova Jolana, Littnerova Simona, Poloczek Martin, Spinar Jindrich, Kubkova Lenka, Kluz Krystyna, Kala Petr, Manousek Jan, Vasku Anna, Parenica Jiri
Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic.
J Appl Genet. 2017 Aug;58(3):331-341. doi: 10.1007/s13353-016-0388-8. Epub 2017 Jan 18.
The influence of polymorphisms in the large group of MMP and TIMP genes on clinical outcomes in patients after ST elevation myocardial infarction (STEMI) treated with primary PCI was analysed. In total, 550 consecutive Caucasian patients with STEMI were included in the present study, with a median of 32 months. We analysed 19 polymorphisms in the genes coding MMP and TIMP genes. The MMP-1 -519A/G and -422A/T polymorphisms are associated with combined endpoint after myocardial infarction. The hazard ratio for AT variant of MMP-1 -422A/T was 1.75 (p < 0.001); the variants with at least one A allele of MMP-1 -519A/G have less risk of combined endpoint. The TT variants of -1562C/T MMP-9 and at least one T allele of +92C/T MMP-13 were considered in a trend to affect disease progression and long-term survival after myocardial infarction. According to reclassification analysis NRI and IDI, long-term risk stratification using MMP-1 -422A/T and -519A/G polymorphisms gives additional information to the commonly used GRACE risk score. Patient stratification after myocardial infraction (MI) according to risk genotypes of MMP-1 polymorphisms could have important clinical implications for identification of patients at risk and therapeutic strategies.
分析了一大组基质金属蛋白酶（MMP）和金属蛋白酶组织抑制因子（TIMP）基因多态性对接受直接经皮冠状动脉介入治疗（PCI）的ST段抬高型心肌梗死（STEMI）患者临床结局的影响。本研究共纳入550例连续的白种人STEMI患者，中位随访时间为32个月。我们分析了编码MMP和TIMP基因的19个多态性。MMP-1 -519A/G和-422A/T多态性与心肌梗死后的联合终点相关。MMP-1 -422A/T的AT变异体的风险比为1.75（p<0.001）；MMP-1 -519A/G至少有一个A等位基因的变异体发生联合终点的风险较低。-1562C/T MMP-9的TT变异体和+92C/T MMP-13至少有一个T等位基因被认为有影响心肌梗死后疾病进展和长期生存的趋势。根据重新分类分析的净重新分类指数（NRI）和综合鉴别改善指数（IDI），使用MMP-1 -422A/T和-519A/G多态性进行长期风险分层可为常用的全球急性冠状动脉事件注册（GRACE）风险评分提供额外信息。根据MMP-1多态性的风险基因型对心肌梗死（MI）患者进行分层，对于识别高危患者和制定治疗策略可能具有重要的临床意义。
