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.

• Klíčová slova
• MMP, Polymorphism, Prognosis, STEMI, TIMP,
• MeSH
• alely MeSH
• dospělí MeSH
• infarkt myokardu s elevacemi ST úseků diagnóza   genetika   MeSH
• koronární angioplastika MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 1 genetika   MeSH
• matrixová metaloproteinasa 13 genetika   MeSH
• matrixová metaloproteinasa 9 genetika   MeSH
• polymorfismus genetický MeSH
• prognóza MeSH
• rizikové faktory MeSH
• senioři MeSH
• tkáňové inhibitory metaloproteinas genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• matrixová metaloproteinasa 1 MeSH
• matrixová metaloproteinasa 13 MeSH
• matrixová metaloproteinasa 9 MeSH
• MMP1 protein, human MeSH Prohlížeč
• MMP13 protein, human MeSH Prohlížeč
• MMP9 protein, human MeSH Prohlížeč
• tkáňové inhibitory metaloproteinas MeSH

PURPOSE: Matrix metalloproteinases (MMPs) are postulated to be involved in the development of retinal angiogenesis through the regulation of extracellular matrix. The objective of the present study was to test for a possible association of five single nucleotide polymorphisms (SNPs) in the MMP-2 gene and two polymorphisms in the MMP-9 gene with proliferative diabetic retinopathy (PDR) and to determine their plasma levels. METHODS: The study comprised 490 Caucasian participants, who were divided into three groups: diabetics with PDR, diabetics without PDR, and nondiabetics. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies determined. Plasma levels of MMP-2 and MMP-9 proteins were analyzed by ELISA. RESULTS: Neither MMP-2 SNPs nor MMP-9 SNPs revealed significant association with PDR in single-locus comparisons; similarly, MMP-2 haplotype frequencies did not differ notably between groups, although the C-allele of the -1306C/T polymorphism and the C-allele containing haplotype (CGCG) in MMP-2 exhibited marginally significant association with PDR in males (p<0.05, p(corr)=NS). Both MMP-2 and MMP-9 plasma levels showed statistically significant differences among the studied groups (p<0.001 and p=0.001, respectively) with highest levels in the PDR group. MMP-2 plasma levels were markedly higher in carriers of either the -1306CC and -1306CT genotypes and (p=0.009) or CGCG haplotype (p=0.043). CONCLUSIONS: These findings indicate that genotype- and haplotype-specific effects on MMP-2 expression corresponding with its plasma levels may contribute to the susceptibility to PDR.

• MeSH
• diabetická retinopatie enzymologie   genetika   patologie   MeSH
• dospělí MeSH
• genetická variace MeSH
• haplotypy MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 krev   genetika   MeSH
• matrixová metaloproteinasa 9 krev   genetika   MeSH
• pohlavní dimorfismus MeSH
• progrese nemoci MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• matrixová metaloproteinasa 2 MeSH
• matrixová metaloproteinasa 9 MeSH