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

BMC Cardiovascular Disorders

Research Article

Tadeusz Osadnik¹  Małgorzata Gonera²  Mariusz Gąsior²  Rafał Reguła²  Bożena Szyguła-Jurkiewicz²  Marek Gierlotka²  Andrzej Lekston²  Kamil Bujak²  Jarosław Wasilewski²  Marcin Gawlita²  Joanna Katarzyna Strzelczyk³  Martyna Fronczek⁴ 

[1] 2nd Department of Cardiology and Angiology, Silesian Center for Heart Diseases, Marii Curie-Skłodowskiej Street 9, 41-800, Zabrze, Poland;Genomics Laboratory, Kardio-Med Silesia Science and Technology Park, Marii Curie-Skłodowskiej Street 10C, 41-800, Zabrze, Poland;3rd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Marii Curie-Skłodowskiej Street 9, 41-800, Zabrze, Poland;Department of Medical and Molecular Biology, School of Medicine with the Division of Dentistry, Medical University of Silesia, Jordana Street 19, 41-808, Zabrze, Poland;Genomics Laboratory, Kardio-Med Silesia Science and Technology Park, Marii Curie-Skłodowskiej Street 10C, 41-800, Zabrze, Poland;Silesian Center for Heart Diseases, Marii Curie-Skłodowskiej Street 9, 41-800, Zabrze, Poland;

关键词: Growth factors;    Atherosclerosis;    Coronary artery disease;    Polymorphism;    VEGF-A;    bFGF;    PDGFB;    TGF-β1;    EGF;   

DOI  :  10.1186/s12872-016-0402-4

 received in 2015-12-04, accepted in 2016-11-08,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundDespite 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.MethodsIn 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).ResultsThere 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.ConclusionsWe 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.

【 授权许可】

CC BY   
© The Author(s). 2016