Genetic Polymorphisms and the Risk of Myocardial Infarction in Patients Under 45 Years of Age

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Abstract

This study investigates the potential role of 17 chosen polymorphisms in 15 candidate genes and the risk of myocardial infarction in patients under 45 years of age. The study consists of 271 patients with myocardial infarction and 141 controls. The analysis of genetic polymorphisms was performed using the PCR–RFLP method. Of the chosen polymorphisms, two (Leu125Val PECAM1 and A1/A2 FVII) are related to myocardial infarction and two (C677T MTHFR and 5A/6A MMP3) to advanced stenosis in arterial vessels (> 75%). We also found that the frequency of some combinations among the analyzed genes and environmental factors varied between the patient and control groups.

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Most cited references 42

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Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease.

Odette Poirier, Christoph Bickel, Jürgen Meyer … (2003)

Matrix metalloproteinase (MMP)-9 secretion by macrophages and other inflammatory cells accelerates atherosclerotic progression and destabilizes vulnerable plaque in animal models. However, epidemiological data evaluating the prognostic impact of circulating concentrations and functional genetic variations of MMP-9 are lacking. In a prospective study of 1127 patients with documented coronary artery disease, we measured baseline plasma MMP-9 levels and determined the MMP-9/C-1562T and MMP-9/R279Q genotypes. During the follow-up period (mean of 4.1 years), 97 patients died from cardiovascular (CV) causes. Median concentrations of MMP-9 were significantly higher among patients who experienced a fatal CV event than among those who did not (62.2 versus 47.8 ng/mL; P<0.0001). The crude hazard risk ratio of CV death associated with increasing quartiles of MMP-9 was 1.4 (95% CI, 1.2 to 1.8; P<0.0001), and after adjustment for clinical and therapeutic confounders, it was 1.3 (95% CI, 1.1 to 1.6; P=0.005). Additional adjustment for highly sensitive CRP, interleukin-6, fibrinogen, and interleukin-18 revealed a hazard risk ratio to 1.2 (95% CI, 0.9 to 1.6; P=0.15). The T allele of the C-1562T polymorphism was associated with increased MMP-9 levels in a fairly codominant fashion (P=0.004). Although none of the polymorphisms was significantly related with future CV death, there was a significant association (P=0.02) between the R279Q polymorphism and CV events in patients with stable angina. Plasma MMP-9 concentration was identified as a novel predictor of CV mortality in patients with coronary artery disease. Whether it provides independent prognostic information compared with other inflammatory markers will have to be additionally assessed.

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Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis.

B. Zhang, S. Ye, S M Herrmann … (1999)

Gelatinase B, a matrix metalloproteinase that has proteolytic activity against connective tissue proteins, has been suggested to be important in the connective tissue remodeling processes associated with atherogenesis and plaque rupture. This study tested the hypothesis that sequence variation in the promoter region of the gelatinase B gene influences its expression, predisposing individuals carrying certain genetic variants to more severe atherosclerosis. Single-strand conformation polymorphism analysis was carried out to search the promoter region of the gene encoding gelatinase B for naturally occurring genetic variation. As a result, an unreported common polymorphism was detected, which arose from a cytosine (C) to thymidine (T) transition at position -1562 relative to the start of transcription. Transient transfection experiments and DNA-protein interaction assays indicated that the T allele had a higher promoter activity than the C allele, which appeared to be due to preferential binding of a putative transcription repressor protein to the C allelic promoter. A sample of 584 male patients with myocardial infarction and 645 age-matched male healthy control subjects were genotyped. The allele frequencies were not significantly different between the cases and control subjects. However, in 374 patients with available angiographic data, 26% of those carrying 1 or 2 copies of the T allele had >50% stenosis in 3 coronary arteries, whereas only 15% of C/C homozygotes had triple-vessel disease. These data suggest that this functional genetic variation influences gelatinase B gene promoter activity in an allele-specific manner and has an effect on atherosclerotic phenotype.

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Biomarkers of atherosclerotic plaque instability and rupture.

Wolfgang Koenig, Natalie Khuseyinova (2007)

Basic research over the last two decades has identified a large number of molecules pertinent to the atherosclerotic process, which have clearly improved our understanding of the underlying pathology. It is now well established that inflammation represents a major feature which is present in the vessel wall throughout all stages of the disease until the final pathophysiologic steps, representing plaque destabilization and eventually plaque rupture. Several cells typical for the atherosclerotic plaque, like monocyte-derived macrophages and T-lymphocytes are able to produce and secrete such mediator molecules, like cytokines, chemokines, growth-factors, enzymes, and disintegrins, which lead to activation of endothelial cells, proliferation of smooth muscle cells, lesion progression, and finally to the weakening of a vulnerable plaque by matrix degradation of its fibrous cap. Today, many of these molecules involved can be measured systemically by sensitive assays, and elevated concentrations in the circulation have been shown to be associated with future cardiovascular events. Determination of several of these molecules carries important prognostic information, independent of traditional risk factors, and may turn out to be useful in improving risk stratification. However, for most of these biomarkers the clinical utility has not yet been established.

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Contributors

: agata.sakowicz@gmail.com

Journal

Journal ID (nlm-ta): Biochem Genet

Journal ID (iso-abbrev): Biochem. Genet

Title: Biochemical Genetics

Publisher: Springer US (Boston )

ISSN (Print): 0006-2928

ISSN (Electronic): 1573-4927

Publication date (Electronic): 30 December 2012

Publication date PMC-release: 30 December 2012

Publication date (Print): April 2013

Volume: 51

Issue: 3-4

Pages: 230-242

Affiliations

[ ]Department of Medical Biotechnology, Medical University of Lodz, Zeligowskiego 7/9, 90-725 Lodz, Poland

[ ]Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland

[ ]Department of Cardiology, Medical University of Lodz, Sterling Str. 1/3, 91-425 Lodz, Poland

[ ]Department of Microelectronics and Computer Science, Lodz University of Technology, ul. Wolczanska, 221/223 Lodz, Poland

Article

Publisher ID: 9558

DOI: 10.1007/s10528-012-9558-5

PMC ID: 3599159

PubMed ID: 23274712

SO-VID: d235012f-9695-45dc-88c9-b8bc26e3f450

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

History

Date received : 19 January 2012

Date accepted : 26 November 2012

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ScienceOpen disciplines: Genetics

Keywords: myocardial infarction,coronary artery disease,atherothrombosis,polymorphism

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ScienceOpen disciplines: Genetics

Keywords: myocardial infarction, coronary artery disease, atherothrombosis, polymorphism

Genetic Polymorphisms and the Risk of Myocardial Infarction in Patients Under 45 Years of Age

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Abstract

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Karger: Cardiovascular System

Most cited references 42

Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease.

Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis.

Biomarkers of atherosclerotic plaque instability and rupture.

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