The effect of endothelial Nitric Oxide Synthase G894T and T786C polymorphisms on Hypoxia-Inducible Factor-1 alpha expression in Sickle Cell Disease
| Autor: | Kostas Konstantopoulos, Revekka Tzanetea, Ioannis Rombos, Iakovos Armenis, Vassiliki Kalotychou |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cancer Research medicine.medical_specialty Nitric Oxide Synthase Type III Physiology Clinical Biochemistry Cell Anemia Sickle Cell 030204 cardiovascular system & hematology Biochemistry Nitric oxide 03 medical and health sciences Hypoxia-Inducible Factor 1-Alpha chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Internal medicine medicine Humans cardiovascular diseases RNA Messenger Aged Polymorphism Genetic business.industry Hypoxia (medical) Middle Aged medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit Hemolysis Pathophysiology 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Multivariate Analysis Female Hemoglobin medicine.symptom business |
| Zdroj: | Nitric oxide : biology and chemistry. |
| ISSN: | 1089-8611 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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