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The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease

BACKGROUND: Despite the important roles of vascular smooth muscle cells and endothelial cells in atherosclerotic lesion formation, data regarding the associations of functional polymorphisms in the genes encoding growth factors with the severity of coronary artery disease (CAD) are lacking. The aim...

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Autores principales: Osadnik, Tadeusz, Strzelczyk, Joanna Katarzyna, Lekston, Andrzej, Reguła, Rafał, Bujak, Kamil, Fronczek, Martyna, Gawlita, Marcin, Gonera, Małgorzata, Wasilewski, Jarosław, Szyguła-Jurkiewicz, Bożena, Gierlotka, Marek, Gąsior, Mariusz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106826/
https://www.ncbi.nlm.nih.gov/pubmed/27835972
http://dx.doi.org/10.1186/s12872-016-0402-4
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author Osadnik, Tadeusz
Strzelczyk, Joanna Katarzyna
Lekston, Andrzej
Reguła, Rafał
Bujak, Kamil
Fronczek, Martyna
Gawlita, Marcin
Gonera, Małgorzata
Wasilewski, Jarosław
Szyguła-Jurkiewicz, Bożena
Gierlotka, Marek
Gąsior, Mariusz
author_facet Osadnik, Tadeusz
Strzelczyk, Joanna Katarzyna
Lekston, Andrzej
Reguła, Rafał
Bujak, Kamil
Fronczek, Martyna
Gawlita, Marcin
Gonera, Małgorzata
Wasilewski, Jarosław
Szyguła-Jurkiewicz, Bożena
Gierlotka, Marek
Gąsior, Mariusz
author_sort Osadnik, Tadeusz
collection PubMed
description BACKGROUND: Despite the important roles of vascular smooth muscle cells and endothelial cells in atherosclerotic lesion formation, data regarding the associations of functional polymorphisms in the genes encoding growth factors with the severity of coronary artery disease (CAD) are lacking. The aim of the present study is to analyze the relationships between functional polymorphisms in genes encoding basic fibroblast growth factor (bFGF, FGF2), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), platelet derived growth factor-B (PDGFB), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor A (VEGF-A) and the severity of coronary atherosclerosis in patients with stable CAD undergoing their first coronary angiography. METHODS: In total, 319 patients with stable CAD who underwent their first coronary angiography at the Silesian Centre for Heart Diseases in Zabrze, Poland were included in the analysis. CAD burden was assessed using the Gensini score. The TaqMan method was used for genotyping of selected functional polymorphisms in the FGF2, PDGFB, TGFB1, IGF1 and VEGFA genes, while rs4444903 in the EGF gene was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The associations between the selected polymorphisms and the Gensini were calculated both for the whole cohort and for a subgroup of patients without previous myocardial infarction (MI). RESULTS: There were no differences in the distribution of the Gensini score between the genotypes of the analyzed polymorphisms in FGF2, EGF, IGF1, PDFGB, and TGFB1 in the whole cohort and in the subgroup of patients without previous MI. The Gensini score for VEGFA rs699947 single-nucleotide polymorphism (SNP) in patients without previous myocardial infarction, after correction for multiple testing, was highest in patients with the A/A genotype, lower in heterozygotes and lowest in patients with the C/C genotype, (p value for trend = 0.013, false discovery rate (FDR) = 0.02). After adjustment for clinical variables, and correction for multiple comparisons the association between the VEGFA genotype and Gensini score remained only nominally significant (p = 0.04, FDR = 0.19) under the dominant genetic model in patients without previous MI. CONCLUSIONS: We were unable to find strong association between analyzed polymorphisms in growth factors and the severity of coronary artery disease, although there was a trend toward association between rs699947 and the severity of CAD in patients without previous MI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12872-016-0402-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-51068262016-11-21 The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease Osadnik, Tadeusz Strzelczyk, Joanna Katarzyna Lekston, Andrzej Reguła, Rafał Bujak, Kamil Fronczek, Martyna Gawlita, Marcin Gonera, Małgorzata Wasilewski, Jarosław Szyguła-Jurkiewicz, Bożena Gierlotka, Marek Gąsior, Mariusz BMC Cardiovasc Disord Research Article BACKGROUND: Despite the important roles of vascular smooth muscle cells and endothelial cells in atherosclerotic lesion formation, data regarding the associations of functional polymorphisms in the genes encoding growth factors with the severity of coronary artery disease (CAD) are lacking. The aim of the present study is to analyze the relationships between functional polymorphisms in genes encoding basic fibroblast growth factor (bFGF, FGF2), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), platelet derived growth factor-B (PDGFB), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor A (VEGF-A) and the severity of coronary atherosclerosis in patients with stable CAD undergoing their first coronary angiography. METHODS: In total, 319 patients with stable CAD who underwent their first coronary angiography at the Silesian Centre for Heart Diseases in Zabrze, Poland were included in the analysis. CAD burden was assessed using the Gensini score. The TaqMan method was used for genotyping of selected functional polymorphisms in the FGF2, PDGFB, TGFB1, IGF1 and VEGFA genes, while rs4444903 in the EGF gene was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The associations between the selected polymorphisms and the Gensini were calculated both for the whole cohort and for a subgroup of patients without previous myocardial infarction (MI). RESULTS: There were no differences in the distribution of the Gensini score between the genotypes of the analyzed polymorphisms in FGF2, EGF, IGF1, PDFGB, and TGFB1 in the whole cohort and in the subgroup of patients without previous MI. The Gensini score for VEGFA rs699947 single-nucleotide polymorphism (SNP) in patients without previous myocardial infarction, after correction for multiple testing, was highest in patients with the A/A genotype, lower in heterozygotes and lowest in patients with the C/C genotype, (p value for trend = 0.013, false discovery rate (FDR) = 0.02). After adjustment for clinical variables, and correction for multiple comparisons the association between the VEGFA genotype and Gensini score remained only nominally significant (p = 0.04, FDR = 0.19) under the dominant genetic model in patients without previous MI. CONCLUSIONS: We were unable to find strong association between analyzed polymorphisms in growth factors and the severity of coronary artery disease, although there was a trend toward association between rs699947 and the severity of CAD in patients without previous MI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12872-016-0402-4) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-11 /pmc/articles/PMC5106826/ /pubmed/27835972 http://dx.doi.org/10.1186/s12872-016-0402-4 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Osadnik, Tadeusz
Strzelczyk, Joanna Katarzyna
Lekston, Andrzej
Reguła, Rafał
Bujak, Kamil
Fronczek, Martyna
Gawlita, Marcin
Gonera, Małgorzata
Wasilewski, Jarosław
Szyguła-Jurkiewicz, Bożena
Gierlotka, Marek
Gąsior, Mariusz
The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease
title The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease
title_full The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease
title_fullStr The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease
title_full_unstemmed The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease
title_short The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease
title_sort association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106826/
https://www.ncbi.nlm.nih.gov/pubmed/27835972
http://dx.doi.org/10.1186/s12872-016-0402-4
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