scholarly journals Association of Endothelial Dysfunction with Endothelin, Nitric Oxide and eNOS Glu298Asp Gene Polymorphism in Coronary Artery Disease

2011 ◽  
Vol 31 (4) ◽  
pp. 215-222 ◽  
Author(s):  
Vandana Saini ◽  
M. K. Bhatnagar ◽  
Jayashree Bhattacharjee
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Gene Polymorphism ◽  
Control Group ◽  
Enos Gene ◽  
The North ◽  
Genotype Frequencies ◽  
Artery Disease

The endothelial dysfunction has been implicated as a major event in the pathogenesis of atherosclerosis. Therefore, this study was planned to determine (a) role of endothelium-derived nitric oxide (NO) and endothelin as coronary artery disease (CAD) risk markers and (b) intergenotypic variation of endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism in CAD.The endothelin, NO and eNOS genotypes were determined in 60 patients with documented history of CAD. These were compared with 50 age- and sex- matched healthy controls. The genotype frequencies for eNOS gene polymorphism were determined by PCR and RFLP. The plasma endothelin in CAD patients was significantly higher (p< 0.001) whereas, the NO level in CAD group was significantly lower (p< 0.001) than the control group. The genotype frequencies for Glu298/Asp (Glu/Glu and Glu/Asp) genotypes were 75% and 25% in CAD subjects and 88% and 12% in control subjects, respectively. No Asp/Asp was found in any of the groups. The genotype frequencies differed significantly (p< 0.05) between the controls and cases. In conclusion, endothelin and NO may be used as markers of endothelial dysfunction in CAD. Asp allele might be a risk factor for CAD in the North Indian population.

scholarly journals NO Level and Endothelial NO Synthase Gene Polymorphism (Glu298Asp) in the Patients with Coronary Artery Disease from the Turkish Population

2004 ◽  
Vol 36 (10) ◽  
pp. 661-666 ◽  
Author(s):  
Lale Afrasyap ◽  
Guler Ozturk
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Gene Polymorphism ◽  
Turkish Population ◽  
Control Group ◽  
Enos Gene ◽  
Nitric Oxide Level ◽  
Significant Difference ◽  
Artery Disease

Abstract Nitric oxide is synthesized from L-arginine by endothelial nitric oxide synthase encoded by eNOS gene. This study was performed to investigate the relationship between the serum nitric oxide level and eNOS gene polymorphism in the Turkish population with angiographically diagnosed coronary artery disease (63.47 ± 9.10 years old, n=250) and control subjects without any history and/or risk factors of coronary artery disease (60.71 ± 9.14 years old, n=150). Griess assay and PCR-RFLP analysis were used to measure the serum nitric oxide metabolites and genotypes, respectively. It was found that Glu/Glu, Glu/Asp and Asp/ Asp genotype frequencies of the eNOS were 49.3%, 41.3% and 9.3% respectively in the control group, and 45.6%, 41.2% and 13.2% in the patient group. Serum nitric oxide levels were (32.56 ± 17.26) μM in controls and (29.84 ± 11.88) μM in patients. Neither the frequencies of the Glu298Asp genotypes nor the serum nitric oxide levels showed a significant difference between the groups. There was also no correlation between serum nitric oxide levels and the frequencies of the eNOS genotypes. Result showed that the coronary artery disease of the Turkish population seemed to develop without any alterations in eNOS Glu298Asp genotype frequency and the serum nitric oxide level.

NCF4 gene polymorphism, level of glutathione and glycated hemoglobin in type 2 diabetics with coronary artery disease

2021 ◽  
pp. 37-47
Author(s):  
Ю.Э. Азарова
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Gene Polymorphism ◽  
Glycated Hemoglobin ◽  
Control Group ◽  
Maldi Tof ◽  
Genotype Frequencies ◽  
Increased Risk ◽  
Artery Disease

Общим патогенетическим звеном сахарного диабета 2 типа (СД2) и ишемической болезни сердца (ИБС) является окислительный стресс, развивающийся в результате дисбаланса продукции активных форм кислорода (АФК) и их обезвреживания системой антиоксидантной защиты. Нейтрофильный цитозольный фактор 4 (NCF4) непосредственно вовлечен в синтез супероксид-аниона в составе НАДФН-оксидазы. Целью настоящего исследования стало изучение ассоциаций восьми однонуклеотидных полиморфизмов гена NCF4 rs5995355 (A>G), rs5995357 (T>A), rs1883112 (G>A), rs4821544 (G>A), rs760519 (T>C), rs729749 (C>T), rs2075938 (G>A) и rs2075939 (C>T) с предрасположенностью к СД2, а также с риском развития ИБС у пациентов с СД2. В исследование включено 1579 пациентов с СД2 (у 448 из которых была также диагностирована ИБС) и 1627 условно здоровых добровольцев. Генотипирование выполнено методом MALDI-TOF масс-спектрометрии на платформе MassArray Analyzer 4. Статистическую обработку полученных данных проводили с помощью онлайн программы SNPStats. Частоты аллелей и генотипов изучаемых SNPs у больных СД2 не отличались от таковых в группе контроля (р>0,05). Установлены ассоциации генотипов rs4821544-C/С (OR 1,71, 95CI 1,12-2,59, р=0,013) и rs5995357-А/А (OR 3,74, 95CI 1,14-12,31, р=0,026) с предрасположенностью к ИБС у больных СД2 женщин. Несмотря на отсутствие ассоциаций изучаемых SNPs гена NCF4 с ИБС у мужчин, именно у представителей мужского пола выявлены ассоциации гаплотипической структуры NCF4 (р=0,0064), а также гаплотипов Н2 (OR 1,79, 95CI 1,16-2,76, р=0,0085) и Н3 (OR 1,77, 95CI 1,06-2,97, р=0,03) с повышенным риском развития ИБС при СД2. Кроме того, выявлены не зависящие от пола ассоциации генотипа rs4821544-С/С с повышенным уровнем гликированного гемоглобина HbA1c (р=0,032) и окисленного глутатиона плазмы крови (p=0.049) у пациентов с ИБС и СД2. В этой же категории больных носительство гаплотипов Н4 rs5995355G-rs5995357A-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938G-rs2075939C и Н10 rs5995355A-rs5995357T-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938A-rs2075939C гена NCF4 ассоциировалось с повышением содержания HbA1c на 8,67% (р=0,011) и 6,27% (р=0,038), соответственно. Полученные данные свидетельствуют о значимом вкладе полиморфизма гена NCF4 в патогенез ИБС у пациентов с СД2 и создают научный задел для разработки таргетной терапии и профилактики этой патологии. A common pathogenic link in type 2 diabetes mellitus (T2D) and coronary artery disease (CAD) is oxidative stress, which develops as a result of an imbalance in the production of reactive oxygen species (ROS) and their neutralization by the antioxidant defense system. Neutrophilic cytosolic factor 4 (NCF4) is directly involved in the synthesis of superoxide anion as part of NADPH oxidase. In this regard, the purpose of this study was to investigate the associations of eight single nucleotide polymorphisms of the NCF4 gene rs5995355 (A>G), rs5995357 (T>A), rs1883112 (G>A), rs4821544 (G>A), rs760519 (T>C), rs729749 (C>T), rs2075938 (G>A), rs2075939 (C>T) with a predisposition to T2D, as well as the risk of developing CAD in patients with T2D. The study included 1579 patients with T2D (448 of them were also diagnosed with CAD) and 1627 relatively healthy volunteers. Genotyping was performed using MALDI-TOF mass spectrometry on the MassArray Analyzer 4 platform. Statistical processing of the obtained data was carried out using the SNPStats online program. The allele and genotype frequencies of the studied SNPs in T2D patients did not differ from those in the control group (p>0.05). Associations of genotypes rs4821544-C/C (OR 1.71, 95CI 1.12-2.59, p=0.013) and rs5995357-A/A (OR 3.74, 95CI 1.14-12.31, p=0.026) with a predisposition to CAD in diabetic females were established. Despite the absence of associations of the studied SNPs NCF4 with CAD in males, associations of the haplotype structure of NCF4 (p=0.0064), as well as the haplotypes H2 (OR 1.79, 95CI 1.16-2.76, p=0.0085) and H3 (OR 1.77, 95CI 1.06-2.97, p=0.03) with an increased risk of CAD were observed exclusively in diabetic males. In addition, a sex-independent relationship of the rs4821544-C/C genotype with an increased level of glycated hemoglobin (p=0.032) and oxidized glutathione (p=0.049) was revealed in patients with CAD and T2D. In the same category of patients haplotypes H4 rs5995355G-rs5995357A-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938G-rs2075939C and H10 rs5995355A-rs5995357T-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938A-rs2075939C of NCF4 gene were associated with an increase in the content of HbA1c 8.67 % (p=0.011) and 6.27% (p=0.038), respectively. The data obtained indicate a significant contribution of the NCF4 gene polymorphism to the pathogenesis of CAD in patients with T2D and create a scientific basis for the development of targeted therapy and prevention of this pathology.

scholarly journals Hyperhomocysteinemia, Endothelial Nitric Oxide Synthase Polymorphism, and Risk of Coronary Artery Disease

2006 ◽  
Vol 52 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Mohsen Kerkeni ◽  
Faouzi Addad ◽  
Maryline Chauffert ◽  
Anne Myara ◽  
Mohamed Ben Farhat ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Nitric Oxide Synthase ◽  
Tunisian Population ◽  
Enos Gene ◽  
Artery Disease ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
G894t Polymorphism

Abstract Background: Hyperhomocysteinemia is an independent, graded risk factor for coronary artery disease (CAD). The G894T variant of endothelial nitric oxide synthase (eNOS) was postulated to be associated with hyperhomocysteinemia and could influence individual susceptibility to CAD. The aims of this study were to investigate (a) the relationship of the eNOS G894T polymorphism with the presence and the severity of CAD and (b) the possible relationship between hyperhomocysteinemia and the eNOS G894T variant for the risk of CAD severity in a Tunisian population. Methods: We used PCR with restriction fragment length polymorphism analysis to detect the G894T variant of the eNOS gene in 100 patients with CAD and 120 healthy controls. The severity of CAD was expressed by the number of affected vessels. Total plasma homocysteine concentrations were determined by direct chemiluminescence assay. Results: The frequencies of the eNOS GG, GT, and TT genotypes in the CAD group were significantly different from those in the control group (45%, 44%, and 11% vs 60%, 35.8% and 4.2%, respectively; P = 0.035). There was no association between the eNOS G894T genotype frequencies and the number of stenosed vessels (P = 0.149). In the CAD group, the coexistence of the 894 GT or TT genotypes and hyperhomocysteinemia led to an increased risk of CAD severity. Conclusion: The G894T polymorphism of the eNOS gene is associated with the presence of CAD, and in conjunction with hyperhomocysteinemia, increased the risk of CAD severity in a Tunisian population.

Response to authentic nitric oxide is preserved in patients with coronary artery disease and endothelial dysfunction

2003 ◽  
Vol 12 (2) ◽  
pp. A62-A63
Author(s):  
Stephen J. Duffy ◽  
Douglas Tomasian ◽  
Monika Holbrook ◽  
John F. Keaney ◽  
Joseph A. Vita
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Artery Disease

scholarly journals Association of Serum Magnesium, Copper and Zinc with Severity of Coronary Artery Disease – A Cross-Sectional Study from Salem, India

2021 ◽  
Vol 10 (37) ◽  
pp. 3262-3266
Author(s):  
Philips Abraham ◽  
Katherine Quintus Jemy ◽  
Sachu Philip ◽  
Krishnan Ramalingam
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Serum Magnesium ◽  
The Body ◽  
Copper Level ◽  
Syntax Score ◽  
Copper Zinc ◽  
Artery Disease

BACKGROUND Coronary artery disease (CAD) remains the principal cause of death and disability in both developed and developing countries. Factors that cause endothelial dysfunction have received increased attention as a potential contributor for atherogenesis. Micronutrients play an important role in maintaining endothelial function as it act as cofactors for number of enzymes. The purpose of this study was to determine plasma level of copper, zinc and magnesium in CAD patients and its correlation with severity of coronary artery disease. METHODS Study group consisted of angiographically positive CAD patients (n = 30) and age and sex matched controls (n = 30). Severity of the CAD was assessed based on the number, location and percentage of stenosis of coronary vessels involved and SYNTAX score was calculated. CAD patients were classified into grade I, II and III based on SYNTAX score. Level of copper, zinc and magnesium in plasma and hemolysate was analysed using atomic absorption spectrometry. Plasma nitric oxide level was also analysed. RESULTS In our study, Plasma copper level was found to be significantly high and zinc copper ratio, hemolysate Mg level were found to be significantly low in CAD patients. The latter parameters were found to have a significant negative correlation with severity of the diseases and with the level of nitric oxide. CONCLUSIONS Even though a number of confounding factors can influence the copper, zinc and magnesium levels in the body, our study shows that levels of these elements have a significant association with severity of coronary artery diseases. KEY WORDS Coronary Artery Disease, Endothelial Dysfunction, Syntax Score

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