Endothelial Nitric Oxide Synthase (eNOS) Gene Polymorphisms and Markers of Hemolysis, Inflammation and Endothelial Dysfunction in Brazilian Sickle Cell Anemia Patients.

Abstract

The impaired bioavailability of endogenous nitric oxide (NO) in sickle cell anemia (SCA) may be influenced by polymorphisms in the endothelial nitric oxide synthase gene (eNOS). We compared allelic/genotypic frequencies of the eNOS polymorphisms T-786C, VNTR4a/b and G894T between 89 adult SCA patients and 100 healthy controls, and investigated the relationship between these SNPs and markers of hemolysis [lactate dehydrogenase (LDH), indirect bilirubin (IB) and reticulocyte counts], inflammation [interleukins IL-1β, IL-6, IL-8, Tumor Necrosis Factor (TNF-α) and C-reactive protein (CRP)] and endothelial dysfunction (ED) [soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble L-selectin (sL-selectin), von Willebrand Factor (vWF) antigen and D-dimers] in the patients. The frequencies of the mutant -786C allele and -786C/C genotype were significantly higher in patients (p = 0.02 and p = 0.04, respectively) but not significantly correlated with the markers. For VNTR4a/b and G894T, the allelic/genotypic frequencies did not statistically differ between patient and control groups. Patients carrying the 4a allele and those with the 894G/G genotype showed a significant decrease in IB (p = 0.02 and p = 0.04, respectively), and only patients with the 4a allele exhibited reduced IL-1β (p = 0.01). The correlation profiles between markers of inflammation and ED significantly differed between patients carrying the mutant alleles and those with wild-type genotypes. This appears to be the first report on the relationship between eNOS gene polymorphisms and markers of hemolysis, inflammation and ED in Brazilian SCA patients. Our results indicate that the SNPs analyzed may influence the phenotypic variability of these patients.

• Authors: F Chenou, D M Albuquerque, D P Leonardo, I F Domingos, M A C Bezerra, A S Araújo, M H S L Blotta, F F Costa, M F Sonati, E V Paula, M N N Santos
• Journal: Biochemical genetics (Biochem Genet) Vol. 58 Issue 4 Pg. 580-594 (Aug 2020) ISSN: 1573-4927 [Electronic] United States
• PMID: 32277314 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Cytokines
• Fibrin Fibrinogen Degradation Products
• ICAM1 protein, human
• Vascular Cell Adhesion Molecule-1
• fibrin fragment D
• von Willebrand Factor
• Intercellular Adhesion Molecule-1
• L-Lactate Dehydrogenase
• NOS3 protein, human
• Nitric Oxide Synthase Type III
• Bilirubin

Topics

• Adult
• Alleles
• Anemia, Sickle Cell (blood, enzymology, epidemiology, genetics)
• Bilirubin (blood)
• Biomarkers (blood)
• Brazil (epidemiology)
• Case-Control Studies
• Cytokines (blood)
• Female
• Fibrin Fibrinogen Degradation Products (analysis)
• Gene Frequency
• Haplotypes
• Hemolysis
• Humans
• Inflammation (blood)
• Intercellular Adhesion Molecule-1 (blood)
• L-Lactate Dehydrogenase (blood)
• Male
• Nitric Oxide Synthase Type III (genetics)
• Polymorphism, Single Nucleotide
• Reticulocyte Count
• Vascular Cell Adhesion Molecule-1 (blood)
• Young Adult
• von Willebrand Factor (analysis)