title: Identification of gene variants related to the nitric oxide pathway in patients with acute coronary syndrome.
abstract: Dysfunction of vascular endothelium is known to have an essential role in the atherosclerotic process by releasing mediators including nitric oxide (NO). Nitric oxide maintains endothelial balance by controlling cellular processes of vascular smooth muscle cells. Evidence suggests that variations in the NO pathway could include atherosclerotic events. The objective of this study was to determine the possible effects of genes on the nitric oxide pathway in the development of acute coronary syndrome (ACS). The blood samples of 100 patients with ACS and 100 controls were collected at Istanbul University, Department of Cardiology. DNA samples were genotyped by using Illumina Cyto-SNP-12 BeadChip. The additive model and Correlation/Trend Test were selected for association analysis. Afterwards, a Q-Q graphic was drawn to compare expected and obtained values. A Manhattan plot was produced to display p-values that were generated by -log10(P) function for each SNP. The p-values under 1×10(-4) were selected as statistically significant SNPs while p-values under 5×10(-2) were considered as suspicious biomarker candidates. Nitric oxide pathway analysis was then used to find the single nucleotide polymorphisms (SNPs) related to ACS. As a result, death-associated protein kinase 3 (DAPK) (rs10426955) was found to be most statistically significant SNP. The most suspicious biomarker candidates associated with the nitric oxide pathway analysis were vascular endothelial growth factor A (VEGFA), methionine sulfoxide reductase A (MSRA), nitric oxide synthase 1 (NOS1), and GTP cyclohydrolase I (GCH-1). Further studies with large sample groups are necessary to clarify the exact role of nitric oxide in the development of disease.
authors.affiliation: Istanbul University, Faculty of Medicine, Department of Cardiology, Capa, Istanbul, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Umman
authors.affiliation: Istanbul University, Institute of Experimental Medicine, Department of Molecular Medicine, Capa, Istanbul, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Cakmakoglu
authors.affiliation: Istanbul University, Institute of Experimental Medicine, Department of Molecular Medicine, Capa, Istanbul, Turkey.
authors.forename: Z B
authors.initials: ZB
authors.lastname: Cincin
authors.affiliation: Istanbul University, Faculty of Medicine, Department of Cardiology, Capa, Istanbul, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Kocaaga
authors.affiliation: Istanbul University, Faculty of Medicine, Department of Cardiology, Capa, Istanbul, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Emet
authors.affiliation: Istanbul University, Faculty of Medicine, Department of Biochemistry, Capa, Istanbul, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Tamer
authors.affiliation: Istanbul University, Faculty of Medicine, Department of Physiology, Capa, Istanbul, Turkey. Electronic address: cahgok@istanbul.edu.tr.
authors.forename: C
authors.initials: C
authors.lastname: Gokkusu
mesh_terms: D054058:Acute Coronary Syndrome / Q000235:genetics*; D015415:Biomarkers; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D064550:Death-Associated Protein Kinases / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism; D006136:GTP Cyclohydrolase / Q000235:genetics; D005838:Genotype; D006801:Humans; D051150:Methionine Sulfoxide Reductases / Q000235:genetics; D009569:Nitric Oxide / Q000235:genetics*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D004247:DNA; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; C579101:DAPK3 protein, human; D064550:Death-Associated Protein Kinases; D006136:GTP Cyclohydrolase
keywords: Acute coronory syndrome; Biomarker; Microarray; Nitric oxide pathway