The effect of endothelial Nitric Oxide Synthase G894T and T786C polymorphisms on Hypoxia-Inducible Factor-1 alpha expression in Sickle Cell Disease

被引：2

作者：

Armenis, Iakovos ^{[1
,2
]}

Kalotychou, Vassiliki ^{[1
]}

Tzanetea, Revekka ^{[1
]}

Konstantopoulos, Kostas ^{[3
]}

Rombos, Ioannis ^{[4
]}

机构：

[1] NKUA, Med Sch, Laiko Gen Hosp, Dept Internal Med 1, Agiou Thoma 17 St, Athens 11527, Greece

[2] Onassis Cardiac Surg Ctr, Dept Cardiol, Syggrou 356 Ave, Kallithea 17674, Greece

[3] NKUA, Med Sch, Laiko Gen Hosp, Dept Hematol, Agiou Thoma 17 St, Athens 11527, Greece

[4] Metropolitan Hosp, Dept Hematol, Ethnarchou Makariou 9 St, Piraeus, Greece

来源：

NITRIC OXIDE-BIOLOGY AND CHEMISTRY | 2021年 / 111卷

关键词：

Sickle cell disease; Hypoxia; HIF-1; alpha; Endothelial nitric oxide synthase; G894T polymorphism; HIF-1-ALPHA; GENE;

D O I：

10.1016/j.niox.2021.03.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hypoxia-Inducible Factor-1 alpha (HIF-1 alpha) 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-1 alpha expression in SCD. We show that G894T polymorphism is a significant predictor of HIF-1 alpha 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-1 alpha expression on the mRNA level and indirectly support the role of nitric oxide in the pathophysiology of SCD.

引用

页码：31 / 36

页数：6

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