부산대학교 도서관

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. • NOS3 G894T polymorphism is related with lower peripheral blood mRNA expression of Hypoxia Inducible Factor-1α (HIF-1α). • HIF-1α expression correlates with Hemoglobin S fraction. • G894T polymorphism, absolute reticulocyte count and Hemoglobin F are independent predictors of HIF-1α expression. • NOS3 T786C polymorphism does not affect HIF-1α expression. [ABSTRACT FROM AUTHOR]