Τίτλος:
The effect of endothelial Nitric Oxide Synthase G894T and T786C polymorphisms on Hypoxia-Inducible Factor-1 alpha expression in Sickle Cell Disease
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Armenis, I.
Kalotychou, V.
Tzanetea, R.
Konstantopoulos, K.
Rombos, I.
Περιοδικό:
Nitric Oxide: Biology and Chemistry
Εκδότης:
Academic Press Inc.
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.niox.2021.03.004
