The Relationship Between eNOS (G894T ) Gene Polymorphism and Arterial Stiffness in Patients with Metabolic Syndrome

Metabolic syndrome (MS) is a clustering entity characterized by obesity, hypertension, hyperglycemia, dyslipidemia, and insulin resistance. Atherosclerotic lesions may be a complication of MS, arising from endothelial dysfunction and induced by decreased nitric oxide (NO) production. NO is synthesized by nitric oxide synthase (eNOS), encoded by the NOS3 gene, and displays anti-inflammatory, vasodilatory, and antiproliferative effects.We aimed to investigate the relationship between the G894T polymorphism of the eNOS gene and metabolic syndrome (including its components) and the association of this polymorphism with arterial function, assessed by determining pulse wave velocity and the augmentation index.The study included 100 consecutive patients, 55% with metabolic syndrome (based on IDF criteria -study group), 45% without MS (control group). Arterial stiffness was measured using TensioMedTMArteriograph. The presence of the homozygous (TT) or heterozygous (GT) state was associated, compared to subjects without the mutation (GG), with an increased prevalence of arterial hypertension, diabetes mellitus, with an increase of abdominal circumference, an increase of triglycerides, without significantly influencing the level of HDL. No significant differences were found between patients with G894T polymorphism compared to those without the mutation regarding the arterial stiffness. The eNOS gene polymorphism: 894G]T was significantly associated with the presence of MS; the polymorphism in homozygous and heterozygous state was associated with an increased risk of metabolic syndrome. G894T polymorphism did not significantly influence the values of the studied arterial parameters (pulse wave velocity, aortic and brachial augmentation index).

NITRIT OKSIDA DAN VOLUME EDEMA OTAK PADA STROK PERDARAHAN DALAM OTAK DENGAN POLIMORFISME G894T (Nitric Oxide and Cerebral Edema Volume in Intracerebral Hemorrhagic Stroke with G894T Polymorphism)

Nitric Oxide (NO) is a vasodilator that regulates vascular smooth muscle tone. Low levels of NO can cause vasoconstriction andhemodynamic disturbances. In stroke the levels of NO are increased. Endothelial nitric oxide synthase gene polymorphism (eNOS) isbelieved to reduce levels of NO in blood. NO levels decreased in stroke patients with G894T polymorphisms of eNOS gene. Mortality rateof hemorrhagic stroke are increased in case with increased peri focal edema volume. The mechanism of the increased of peri focal edemavolume completely unknown yet, suspected genetics factor. This study was conducted to know the correlation between the NO and perifocal edema volume in stroke with eNOS gene G894T polymorphism by determination. The study was conducted by comparing the levelsof NO and edema volume of intra cerebral hemorrhagic stroke of 46 subjects from Neurology department of dr. Zainoel Abidin generalhospital in Banda Aceh from September 2014 through January 2015 with comparison to ischemic stroke patients the same amount.NO levels checked with Cayman Systems kit following the protocol Griess. G894T polymorphism was determined by PCR-RFLP method.The volume of edema was measured with semi-automatic CT volumetry. Chi Square test was used for comparison of two variables andSpearman correlation test to assess the relationship between the NO and perifocal edema volume. The result is significant, if p valuewas <0.05. The results of these study were levels of NO decreases if there were polymorphism (p=0.001). Peri focal edema volume wasincreased if there were G894T polymorphism (p=0.038). The correlation between low levels of NO and increase of edema volume wasobtained p=0.040 and R=0.304. The researchers concluded that in intra cerebral hemorrhagic stroke the level of NO were decreasedand peri focal edema volume increased if there was G894T polymorphism of eNOS gene. There was a less correlation between low levelsof NO and peri focal edema volume.

Prooxidant-antioxidant balance depending on endothelial nitric oxide synthase G894T polymorphism

The aim of the study was to assess the prooxidant-antioxidant balance depending on endothelial nitric oxide synthase G894T polymorphism. The frequency distribution of alleles and genotypes of G894T polymorphism, nitrite concentration, hydrogen sulphide, lipid peroxidation products (diene conjugates, malonic dialdehyde), antioxidants (reduced glutathione, catalase, ceruloplasmin, retinol) were determined in venous blood of healthy males. The incidence of the GG genotype was 49.1%, GT – 44.2%, TT – 6.7%. The level of malonic dialdehyde in erythrocytes with the GG genotype is 16.8% lower than in the genotype GT. The concentration of hydrogen sulphide in the blood with the GG genotype was 27.5 [18,2; 32,5] mM, GT – 28.6 [22.9; 33.8] mM, TT – 36.3 [33.8; 42.5] mM. The content of total nitrites in plasma with the GG genotype was 10.4 [9,0; 12,5] mM, GT – 10.4 [8.9; 11.8] mM, TT – 9.4 [8.8; 9.8] mM. The genotype GG causes a lower level of malonic dialdehyde in comparison with the heterozygous genotype. The G894T polymorphism allele T is associated with a low content of total nitrites in the plasma and a high concentration of hydrogen sulfide. The data obtained suggest that if the oxygen supply of the organism is impaired, the endothelial nitric oxide synthase G894T polymorphism may be important for the oxidative stress development.