@article{3077108,
    title = "The effect of endothelial Nitric Oxide Synthase G894T and T786C polymorphisms on Hypoxia-Inducible Factor-1 alpha expression in Sickle Cell Disease",
    author = "Armenis, I. and Kalotychou, V. and Tzanetea, R. and Konstantopoulos, K. and Rombos, I.",
    journal = "Nitric Oxide: Biology and Chemistry",
    year = "2021",
    volume = "111-112",
    pages = "31-36",
    publisher = "Academic Press Inc.",
    issn = "1089-8603, 1089-8611",
    doi = "10.1016/j.niox.2021.03.004",
    keywords = "C reactive protein;  DNA;  endothelial nitric oxide synthase;  genomic DNA;  hemoglobin;  hypoxia inducible factor 1alpha;  messenger RNA;  nitric oxide;  reactive oxygen metabolite;  transcription factor;  vasculotropin;  endothelial nitric oxide synthase;  HIF1A protein, human;  hypoxia inducible factor 1alpha;  messenger RNA;  NOS3 protein, human, adult;  Article;  clinical article;  controlled study;  disease exacerbation;  disease severity;  DNA polymorphism;  female;  gene expression;  hemolysis;  human;  laboratory test;  male;  middle aged;  multiple regression;  oxidative stress;  pathophysiology;  prognosis;  reverse transcription polymerase chain reaction;  sickle cell anemia;  upregulation;  aged;  blood;  genetic polymorphism;  genetics;  metabolism;  multivariate analysis;  sickle cell anemia, Aged;  Anemia, Sickle Cell;  Female;  Humans;  Hypoxia-Inducible Factor 1, alpha Subunit;  Male;  Middle Aged;  Multivariate Analysis;  Nitric Oxide Synthase Type III;  Polymorphism, Genetic;  RNA, Messenger",
    abstract = "Hypoxia-Inducible Factor-1α (HIF-1α) expression is upregulated in Sickle Cell Disease (SCD) and correlates with various laboratory markers of disease severity. Nitric Oxide plays a pivotal role in SCD pathophysiology and endothelial Nitric Oxide Synthase (NOS3) polymorphisms affect prognosis and laboratory parameters. This study questions the effect of NOS3 G894T and T786C polymorphisms on HIF-1α expression in SCD. We show that G894T polymorphism is a significant predictor of HIF-1α expression. Its effect is exerted independently of hemolysis/hemoglobin fragment concentrations, as shown in multiple regression analysis. Our results establish a novel modulator of HIF-1α expression on the mRNA level and indirectly support the role of nitric oxide in the pathophysiology of SCD. © 2021 Elsevier Inc."
}