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
• Alleles MeSH
• Adult MeSH
• ST Elevation Myocardial Infarction diagnosis   genetics   MeSH
• Percutaneous Coronary Intervention MeSH
• Middle Aged MeSH
• Humans MeSH
• Matrix Metalloproteinase 1 genetics   MeSH
• Matrix Metalloproteinase 13 genetics   MeSH
• Matrix Metalloproteinase 9 genetics   MeSH
• Polymorphism, Genetic MeSH
• Prognosis MeSH
• Risk Factors MeSH
• Aged MeSH
• Tissue Inhibitor of Metalloproteinases genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Matrix Metalloproteinase 1 MeSH
• Matrix Metalloproteinase 13 MeSH
• Matrix Metalloproteinase 9 MeSH
• MMP1 protein, human MeSH Browser
• MMP13 protein, human MeSH Browser
• MMP9 protein, human MeSH Browser
• Tissue Inhibitor of Metalloproteinases MeSH

Genetic and non-genetic predictors of 15-year survival in patients with chronic three-vessel disease (3VD) were investigated. Coronary angiography was performed on 810 subjects with symptoms of stable ischemic heart disease in 1998. The patients with 3VD were genotyped for 23 candidate polymorphisms covering the PPAR-RXR pathway, matrix metalloproteinase-2, renin-angiotensin-aldosterone system, endothelin-1, cytokine genes, MTHFR and APO E variants. Fifteen-year survival data were obtained from the national insurance registry. All data were available in the case of 150 patients with 3VD. Statistical analysis used stepwise Cox regression with dominant, recessive, or additive mode of genetic expression. Involved variables included age, sex, BMI, blood pressure, diabetes, ejection fraction, left main stenosis, previously diagnosed coronary stenosis, myocardial infarction in personal history, and coronary bypass along with polymorphisms pre-selected by log-rank tests. Out of the 23 polymorphisms, four were included in the model construction. SNP in the IL-6 gene rs1800795 (-174 G/C) has been found to be a significant predictor of survival. This SNP was in a linkage disequilibrium with rs1800797 (-597 G/A) in the same gene (D'=1.0), which was also found to constitute a significant predictor of survival when rs1800795 was not included in the model construction. Age, increased BMI, diabetes, low EF, and left main stenosis were also significant predictors in all models. Age, increased BMI, diabetes, low ejection fraction, left main stenosis, and genetic variation in the IL-6 promoter were established as significant independent risk factors for the survival of patients with three-vessel disease.

• MeSH
• DNA genetics   MeSH
• Genetic Predisposition to Disease * MeSH
• Interleukin-6 blood   genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Coronary Artery Disease diagnostic imaging   genetics   mortality   MeSH
• Polymerase Chain Reaction MeSH
• Polymorphism, Genetic * MeSH
• Forecasting * MeSH
• Prognosis MeSH
• Proportional Hazards Models MeSH
• Radiography MeSH
• Registries * MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• DNA MeSH
• Interleukin-6 MeSH

AIM: The purpose of this study was to assess the associations of polymorphisms in two metalloproteinase genes-metalloproteinase-2 (MMP-2) and angiotensin converting enzyme (ACE)-with clinical response to autologous transplantation of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction. METHODS: The double centre study included 48 patients with a first acute myocardial infarction treated with primary coronary angioplasty, stent implantation and transplantation of MBMC. According to the changes in perfusion defect size, left ventricle ejection fraction, end-systolic volume and peak systolic velocity of the infracted wall (dSaMI) after cell therapy, the patients were retrospectively divided into group A (responders) and group B (non-responders). Genomic DNA was isolated from peripheral leukocytes by a standard technique using proteinase K. Three MMP-2 promoter (-1575G/A, -1306C/T and -790T/G) as well as I/D ACE gene polymorphisms were detected by PCR methods with restriction analyses (when necessary) according to standard protocols. RESULTS: Of the 48 patients who received MBMC transplantation, 17 responded to the therapy. There were no significant differences in the prevalence of matrix metalloproteinase-2 triple genotype GGCCTT between responder/non-responder groups (71% versus 61%, p=0.375). Similarly, no differences in either genotype distribution or allelic frequencies of I/D ACE polymorphism between responders and non-responders to the cell therapy were observed (p=0.933). Compared to patients with ACE genotype ID or DD, the patients with ACE II genotype significantly improved in regional systolic LV function of the infarcted wall after implantations of MBMC (dSaMI - 0.4 versus 1.4 cm/s, p=0.037). CONCLUSION: In our study, the ACE genotype II was associated with improvement of regional systolic LV function of the infarcted wall after implantations of MBMC. The detected polymorphism in matrix metalloproteinase-2 gene was not associated with clinical response to cell therapy.

• MeSH
• Alleles MeSH
• Peptidyl-Dipeptidase A genetics   MeSH
• Gene Frequency genetics   MeSH
• Ventricular Function, Left physiology   MeSH
• Genotype * MeSH
• Myocardial Infarction genetics   physiopathology   therapy   MeSH
• Myocardial Contraction physiology   MeSH
• Humans MeSH
• Matrix Metalloproteinase 2 genetics   MeSH
• Cell Count MeSH
• Polymerase Chain Reaction MeSH
• Polymorphism, Genetic genetics   MeSH
• Promoter Regions, Genetic genetics   MeSH
• Stents MeSH
• Bone Marrow Transplantation * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH
• Names of Substances
• Peptidyl-Dipeptidase A MeSH
• Matrix Metalloproteinase 2 MeSH
• MMP2 protein, human MeSH Browser

The aim of the study was to investigate the DNA polymorphic genotype in MMP-2 promoter gene as a potential candidate region for the development of the cutaneous T-cell lymphoma (CTCL) and/or its progression. A total of 89 Czech patients with CTCL (including 23 patients with large plaque parapsoriasis) were compared to 198 controls of similar age and sex distribution, without personal or family history of chronic skin diseases and without personal history of malignancy. The three selected polymorphisms in the promoter of MMP-2 gene (-1575G/A, -1306C/T, and -790T/G) were determined using the PCR-based methodology with RFLP. In our cohort, the associated GGCCTT MMP-2 promoter genotype was highly significantly more frequent in CTCL-Ia stage patients compared to patients with parapsoriasis, the tests having high sensitivity and specificity (78%, 83%, resp.). To conclude, use of associated MMP-2 promoter genotype as a DNA marker might make it possible to distinguish between the patients with parapsoriasis and those with CTCL stage Ia, which could substantially improve possibilities of clinical diagnostics, therapy design, and prognosis of this serious condition in the early stages.

• MeSH
• Adult MeSH
• Genetic Predisposition to Disease MeSH
• Lymphoma, T-Cell, Cutaneous enzymology   genetics   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Matrix Metalloproteinase 2 genetics   MeSH
• Biomarkers, Tumor genetics   MeSH
• Skin Neoplasms enzymology   genetics   pathology   MeSH
• Parapsoriasis genetics   MeSH
• Promoter Regions, Genetic * MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Matrix Metalloproteinase 2 MeSH
• Biomarkers, Tumor 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
• Diabetic Retinopathy enzymology   genetics   pathology   MeSH
• Adult MeSH
• Genetic Variation MeSH
• Haplotypes MeSH
• Middle Aged MeSH
• Humans MeSH
• Matrix Metalloproteinase 2 blood   genetics   MeSH
• Matrix Metalloproteinase 9 blood   genetics   MeSH
• Sex Characteristics MeSH
• Disease Progression MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Matrix Metalloproteinase 2 MeSH
• Matrix Metalloproteinase 9 MeSH