Relationship of long-term prognosis to MMP and TIMP polymorphisms in patients after ST elevation myocardial infarction

J Appl Genet. 2017 Aug;58(3):331-341. doi: 10.1007/s13353-016-0388-8. Epub 2017 Jan 18.

Abstract

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.

Keywords: MMP; Polymorphism; Prognosis; STEMI; TIMP.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Middle Aged
  • Percutaneous Coronary Intervention
  • Polymorphism, Genetic
  • Prognosis
  • Risk Factors
  • ST Elevation Myocardial Infarction / diagnosis
  • ST Elevation Myocardial Infarction / genetics*
  • Tissue Inhibitor of Metalloproteinases / genetics*

Substances

  • Tissue Inhibitor of Metalloproteinases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • MMP1 protein, human
  • Matrix Metalloproteinase 1