Nitric Oxide Synthase Gene Polymorphisms Research Articles

Erectile dysfunction in cardiovascular patients: A prospective study of the eNOS gene T‐786C, G894T, and INTRON variable number of the tandem repeat functional interaction

AbstractBackgroundCardiovascular disease induces erectile dysfunction modulated by endothelial nitric oxide synthase enzyme and an impaired ejection fraction that restricts penis vascular congestion. However, the mechanisms regulating endothelial dysfunction are not understood.ObjectivesExploring the functional impact of endothelial nitric oxide synthase genetic polymorphisms on erectile dysfunction and drug therapy optimization in high‐risk cardiovascular disease patients.Materials and methodsPatients with erectile dysfunction symptoms and candidates for andrology therapy were included (n = 112). Clinical data and endothelial nitric oxide synthase rs1799983 (G894T) and rs2070744 (T‐786C), genotyped by fluorescence polarization assays, were registered. The 27‐bp variable number of the tandem repeat polymorphism in intron 4 (intron4b/a) was analyzed by polymerase chain reaction‐restriction fragment length polymorphism. Association analyses were run with the R‐3.2.0 software.ResultsA significant association between endothelial nitric oxide synthase 786‐TT (p = 0.005) and the aa/ac of intron 4 variable number of the tandem repeat (p = 0.02) with higher erectile dysfunction susceptibility was observed in cardiovascular disease patients (60 ± 9 years, 66% severe erectile dysfunction, 56% ejection fraction). After 3‐months of phosphodiesterase type 5 inhibitors, erectile dysfunction (International Index of Erectile Function, 50 ± 16 scores, the International Index of Erectile Function‐Erectile Function 21 ± 10 scores, p < 0.001) and sexual quality of life (modified Sexual Life Quality Questionnaire 55 ± 23 scores, p < 0.001) had significantly improved. The cardiovascular ejection fraction was influenced positively with better sexual quality of life (0.1941), and also in the endothelial nitric oxide synthase G894‐T allele (p = 0.076) carriers, which could merit future analyses. Erectile dysfunction was present as the primary clinical manifestation in 62% of cases, with cardiovascular disease occurring concurrently. Only former smokers and obese subjects debuted prior to cardiovascular disease than to erectile dysfunction.ConclusionsOur study provides comprehensive insights into the functional interaction linking endothelial nitric oxide synthase gene polymorphisms, erectile function, and ejection fraction in high‐risk cardiovascular disease patients. Future therapeutic strategies could target endothelial nitric oxide synthase activity by including lifestyle changes and epigenetic modulations.

Association between nitric oxide synthase (NOS3) gene polymorphisms and diabetic nephropathy: An updated meta-analysis

Polymorphisms located within NOS3 gene have been investigated as susceptibility variants for diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM) in a large number of studies. However, these previous articles yielded inconsistent results and we aimed at elucidating the impact of NOS3 variants on DN risk in T2DM by conducting an updated systematic data synthesis. A total of 36 studies (12,807 participants) were selected for qualitative data synthesis, while 33 records with 11,649 subjects were included in the meta-analysis. The pooled analysis demonstrated the association of minor alleles of rs2070744 and rs1799983 with an increased susceptibility to DN (P < 0.001 and P = 0.015 for allelic model, respectively). For both of these variants, a significant effect of subgrouping according to ethnicity was found. Rs869109213 displayed an association with DN susceptibility, with pooled effect measures indicating a predisposing effect of the minor allele a (Prec = 0.002, ORrec = 1.960, 95%CI 1.288–2.983; Paavs. bb = 0.001, ORaavs. bb = 2.014, 95%CI 1.316–3.083). These findings support the effects of NOS3 variants on the risk of developing DN in T2DM.

Inducible Nitric Oxide Synthase Gene Polymorphism and Markers of Pro-inflammatory Endothelial Dysfunction in Coronary Artery Disease: Case Control Study in North Indian Population

Inducible Nitric Oxide Synthase Gene Polymorphism and Markers of Pro-inflammatory Endothelial Dysfunction in Coronary Artery Disease: Case Control Study in North Indian Population

The association of rs1799983 eNOS gene polymorphism with dyslipidemia and efficacy of atorvastatin in correction of lipid exchange disorders in patients with diabetic nephropathy and essential hypertension

Objective — to search an association of rs1799983 endothelial nitric oxide synthase (eNOS) gene polymorphism with dyslipidemia (DLP) and the efficacy of atorvastatin used in correction of lipid exchange disorders in patients with diabetic nephropathy (DN) and essential hypertension (EH).&#x0D; Materials and methods. The study had been conducted in the clinical Department of Arterial Hypertension and Kidney Disease at L. T. Mala National Therapy Institute of NAMS of Ukraine (Kharkiv). Clinical examinations involved 89 patients (pts) (43(48.3%) females and 46(51.7%) males) with DN of II—IV stages and EH of II—III stages aged 34 to 78 years old (an average age is 57.11±1.89 years old). They were also genotyped for rs1799983 eNOS gene polymorphism (G894T) with a use of polymerase chain reaction. GG genotype was revealed in 29(32.6%) of pts, GT genotype was found in 33(37.1%) of cases and 27(30.3%) participants of the study had TT genotype. With the use of immune enzyme method, serum levels of total cholesterol (TC), high‑density lipoprotein cholesterol (HDL‑C) and triglycerides (TG) were measured in all included pts. Very low density lipoprotein cholesterol (VLDL‑C), low‑density lipoprotein cholesterol (LDL‑C), non‑HDL‑C and coefficient of atherogenicity were calculated by known formulas. Atorvastatin was prescribed to all the pts included in study for correction of lipid exchange disorders in daily doses of 10—20 mg (an average daily dose was 16.7±0.91 mg) for 24 weeks.&#x0D; Results. Rs1799983 eNOS gene polymorphism in pts with DN and EH was found to be associated with lipid parameters characterized a phenotype of diabetic DLP with its peculiar disorders in the systems of reverse cholesterol transport and lipoprotein lipolysis of TG‑containing VLDL. In this case a dominant G allele was associated with less significant lipid disorders than a recessive T allele. A homozygous state with allele G (genotype GG) in pts with DN and EH was associated with abnormalities in the system of TG‑containing VLDL lipolysis and an appearance of T allele in genotype (genotypes GT and TT) made an additional negative contribution to the state of lipid exchange and transport. In pts with genotype GT abnormalities in reverse cholesterol transport added to disorders in the system of TG‑containing VLDL lipolysis and in pts with genotype TT there was a combination of disorders in the systems of direct, reverse cholesterol transport and lipoprotein lipolysis. The study of hypolipidemic effects of atorvastatin depended on genotype of rs1799983 eNOS gene polymorphism showed that in GG genotype atorvastatin demonstrated mainly a hypocholesterolemic action while in genotypes contained T allele (GT and TT) we observed a reduction of hypocholesterolemic effect against the background of significant hypotriglyceridemic action and elevation of HDL‑C.&#x0D; Conclusions. In pts with DN and EH rs1799983 eNOS gene polymorphism was associated with diabetic DLP. A recessive allele T was associated with significant lipid disorders compared with a dominant G allele. A significant hypocholesterolemic effect of atorvastatin was observed in case of a presence of G allele in pts genotype while a presence of T allele in pts genotype (GT and TT) was associated with a reduction of atorvastatin cholesterol lowering action.&#x0D;

Multifactorial model for prediction of the development of polymorphic ventricular tachycardia in patients with drug-induced QT interval prolongation induced by class III antiarrhythmic drugs

Aim. To develop a multifactorial model for predicting the development of polymorphic ventricular tachycardia (VT) in patients with drug-induced long QT syndrome (LQTS) induced by class III antiarrhythmic drugs (AADs) by identifying electrocardiographic, laboratory and molecular genetic predictors.Methods. The study included 64 patients (37 (57.9%) women and 27 (42.1%) men, mean age 57.2±9.4 years) with ischemic heart disease and/or arterial hypertension. and cardiac arrhythmias, in which drug-induced prolongation of the QTc interval (Bazett) (over 450 ms in men and over 470 ms in women) was noted with the use of class III AADs (amiodarone or sotalol) in a cardiac hospital. Depending on the presence or absence of non-sustained polymorphic VT according to 24-hour ECG Holter monitoring, patients were further divided into two groups: 17 patients with episodes of non-sustained polymorphic VT and 47 patients without such episodes. All patients underwent clinical and laboratory, instrumental and molecular genetic studies, which included taking an anamnesis, recording ECG in 12 leads, biochemical blood test, determining the levels of neuronal NO-synthase (NOS1) and the adapter protein of neuronal NO-synthase (NOS1AP) in blood serum by enzyme immunoassay, determination of nitric oxide synthase gene polymorphisms by polymerase chain reaction. To assess the relationship of the studied parameters with the achievement of the end point, the method of logistic regression with a binary response and the logit function of the connection was used.Results. To assess the risk of developing non-sustained polymorphic VT in patients with drug-induced LQTS while taking class III AADs, a complex binary logistic regression model was developed, including the following indicators: patient gender (p=0.019), relative variance of the QT interval (p=0.002), duration of the Tpeak-Tend interval, (p=0.034), serum magnesium (p=0.004) and NOS1 (p=0.004) levels, as well as the AA genotype of the G84A polymorphism of the NOS1 gene (p=0.049). With the calculated value of the threshold probability p≥0.48, the developed model makes it possible to identify patients at high risk of developing polymorphic VT in patients with drug-induced LQTS with a sensitivity of 94.12%, a specificity of 89.36%, and an area under the ROC curve of 0.977 (0.95-1.0, p&lt;0.001).Conclusion. The developed complex model will allow predicting the risk of proarrhythmic effects in patients with drug-induced LQTS, which will lead to a decrease in the number of cardiovascular events in this category of patients.

ENOS polymorphisms on male infertility: An updated systematic review and meta-analysis.

This meta-analysis was performed to examine the association of 3 endothelial nitric oxide synthase (eNOS) gene polymorphisms with male infertility. The literature on the relation between the mutant of eNOS and male infertility before July 1, 2022, was conducted in Pubmed, Medline, and Web of Science. The search strategy is as follows: (eNOS OR ECNOS OR nitric oxide synthase 3 OR NOS3) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (male infertility). Statistical analysis was performed with the web of MetaGenyo, Stata 12, trial sequential analysis 0.9Beta, and the web of GTEx. Overall, 13 studies (26 case-controls) were included involving 6518 cases and 5461 controls for 3 polymorphisms (rs2070744, rs1799983, rs61722009) of eNOS. We found that eNOS rs2070744 was correlated with an increased risk of male infertility (C vs. T: odds ratio [OR], 1.48; 95% confidence interval [CI], [1.19-1.85]; CC vs. TT: OR, 2.59; 95% CI, [1.40-4.80]; CT vs. TT: OR, 1.17; 95% CI, [1.00-1.38]; CC vs. CT + TT: OR, 2.50; 95% CI, [1.35-4.62]; CC + CT vs. TT: OR, 1.41; 95% CI, [1.21-1.64]). And eNOS rs1799983 was correlated with an increased risk of male infertility (allele contrast T vs. G: OR, 1.41; 95% CI, [1.01-1.96]; P = .043; recessive model TT vs. TG + GG: OR, 2.00; 95% CI, [1.03-3.90]; P = .042). In the stratified analysis of rs61722009, we found Asians might be correlated with an increased risk of male infertility (4a vs. 4b: OR, 1.50; 95% CI, [0.94-2.38]; 4a4a vs. 4b4b: OR, 2.56; 95% CI, [0.70-9.38]; 4a4b vs. 4b4b: OR, 1.36; 95% CI, [0.87-2.13]; 4a4a vs. 4a4b + 4b4b: OR, 2.57; 95% CI, [0.91-7.30]; 4a4a + 4a4b vs. 4b4b: OR, 1.44; 95% CI, [0.87-2.40]). The eNOS rs2070744 polymorphism and rs1799983 are associated with the risk of male infertility, and rs61722009 might be a risk factor for Asians.

Association of endothelial nitric oxide synthase (Glu298Asp) gene polymorphism with radial artery spasm during cardiac catheterization in Egyptians

BackgroundNitric oxide (NO) exerts diverse effects on the cardiovascular system. Impairment of NO production plays a key role in cerebral and coronary artery spasm. We aimed to explore the predicting factors of radial artery spasm (RAS) and the association of eNOS gene polymorphism (Glu298Asp) with RAS during cardiac catheterization.Methods and results200 patients underwent elective coronary angiography through a trans-radial approach. The subjects were genotyped to the Glu298Asp polymorphism (rs1799983) on the eNOS gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results showed that the subjects with the TT genotype and T allele were significantly more likely to develop radial artery spasms (OR = 12.5, 4.6, P < 0.001 respectively). TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, radial tortuosity, and right radial access are independent predictors of radial spasm.ConclusionThe eNOS (Glu298Asp) gene polymorphism is associated with RAS during cardiac catheterization in Egyptians. TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, right radial access, and tortuosity are independent predictors of RAS during cardiac catheterization.

Association between inducible nitric oxide synthase-954-G&gt;C and Ex16+14-C&gt;T gene polymorphisms and susceptibility to psoriasis and psoriatic arthritis

Background Psoriasis is a prevalent disorder of primarily skin and joint affection with a well-known genetic background and a sophisticated pathogenesis. The inducible nitric oxide synthase (iNOS) gene polymorphisms are unexplored areas of research when it comes to psoriasis. Objectives The aim of the study was to investigate the probable link between iNOS gene polymorphisms (-954 G/C and Ex 16+14C/T) and susceptibility to psoriasis and psoriatic arthritis (PsA). Patients and methods We included three groups of participants: 100 participants each of psoriasis, PsA and healthy controls. Genetic polymorphism analysis was performed utilizing the PCR with the restriction fragment length polymorphism method. Results Genetic analysis of iNOS polymorphism at Ex 16+14C/T revealed significantly increased CT genotype frequency and significantly lower CC genotype frequency in psoriasis (P=0.0011, 0.003, respectively) and PsA patients (P=0.001, P&lt;0.0001, respectively) in comparison to controls. Genetic analysis of iNOS polymorphism at −954 G/C revealed insignificant difference in genotype distribution between psoriasis patients and controls, whereas significantly increased GC genotype frequency (P=0.038) and significantly decreased GG genotype frequency (P=0.038) were detected in PsA patients versus healthy controls. Conclusions iNOS polymorphism at Ex 16+14C/T, particularly the CT genotype, is associated with psoriasis in Egyptians, whereas PsA is associated with polymorphism at Ex 16+14 and −954G/C.

Effect of nitric oxide synthase gene polymorphism on inflammatory response in patients with chronic obstructive pulmonary disease

This study aimed to investigate the association between nitric oxide synthase gene polymorphisms and the inflammatory responses in patients with ‘fast-’ and ‘slow-’ developing chronic obstructive pulmonary disease (COPD). In the main process, 190 patients with slow-developing COPD, 94 patients with fast-developing COPD and 105 healthy volunteers were selected for inclusion. Endothelial nitric oxide synthase (eNOS) was detected using western-blot eNOS sites, and inducible nitric oxide synthase (iNOS) was detected through SNPshot. T helper 17 cells (Th17) and regulator T (Treg) cells were detected via flow cytometry, and interferon-gamma, tumour necrosis factor-alpha, interleukin (IL)-17, IL-10, IL-6, IL-4 and IL-2 were detected using a cytometric bead array. The final results and conclusions drawn from the tests suggest that Th17/Treg-mediated immune inflammation plays an important role in the pathogenesis of COPD, but whether it affects the development of COPD needs further investigation. Overall, COPD patients with a young age of onset, young age of smoking initiation and small body mass index, as well as COPD patients with CC at rs3729508 in the iNOS gene and non-GG at rs7830 in the eNOS gene, may be more likely to contract fast-developing COPD.

Association of nitric oxide synthase gene polymorphism with asthma: A systematic review and meta-analysis.

This study examines the associations between asthma and nitric oxide (NO) synthase (NOS) gene polymorphisms. After a systematic literature search in electronic databases, studies were selected based on eligibility criteria. Data were extracted from research articles and were synthesized and tabulated. Where a particular polymorphism data were reported by multiple studies, meta-analyses of odds ratios were performed, or odds ratios reported by individual studies were pooled. Twenty studies (4450 asthma patients and 5306 non-asthmatic individuals) were identified. Many studies did not find any association between CCTTT repeat polymorphism in NOS2 gene and asthma. However, a study reported that pretreatment mean exhaled NO levels in asthmatics were found to be significantly higher in genotypes with higher number of CCTTT repeats. Also, alleles with <11 CCTTT repeats were associated with poor asthma treatment outcomes. A single nucleotide polymorphism, G894T, in NOS3 gene was not found to be significantly associated with asthma by at least four studies. However, a T allele at this locus was associated with lower NO levels. Also, G894T frequency was significantly higher in asthmatic children who responded to inhaled corticosteroids along with long-lasting beta2-agonists. A T allele of NOS3 786C/T polymorphism increased the probability of bronchial asthma with comorbid essential hypertension in asthma patients. Asthma severity also differed for different Ser608Leu exon 16 variants of NOS2 gene. Several polymorph NOS gene variants are identified, some of which appear to have influence on asthma prevalence or outcomes. However, data are varying depending on the nature of variant, ethnicity, study design, and disease parameters.

Polymorphism of NOS3 gene and its association with essential hypertension in Guizhou populations of China.

A case-control study was conducted to evaluate the relationship between endothelial nitric oxide synthase (NOS3) gene polymorphism and essential hypertension in the Han, Miao, and Buyi populations in Guizhou China. DNA was collected from the blood samples of 353 essential hypertension patients and 342 healthy controls from Guizhou province of China. Eight polymorphisms of the NOS3 gene were genotyped using the Sequenom MassARRAY platform. For genetic analysis, SPSS 26.0, Haploview, SNPStats, SHEsis, and MDR were utilized. All SNPs (rs11771443, rs1808593, rs753482, rs3918186, rs3918188, rs3918227, rs7830, and rs891512) satisfied the Hardy-Weinberg equilibrium test (P > 0.05). The allele and genotype frequencies of rs7830 and rs1808593 in case-control groups demonstrated significant differences (P < 0.05). Compared to the TT genotype of rs1808593, the TG or GG genotype reduced the risk of hypertension in the Miao population (OR = 0.410, 95% CI: 0.218-0.770, P = 0.006). Compared to the GG or GT genotype of rs7830, the TT genotype increased the risk of hypertension in the overall populations (OR = 1.716, 95%CI: 1.139-2.586, P = 0.010). The CATT (rs3918227-rs391818186-rs1808593-rs7830) haplotype was a risk factor for hypertension in the Miao and Han populations (OR = 1.471, 95%CI: 1.010-2.143, P = 0.044 and OR = 1.692, 95%CI: 1.124-2.545, P = 0.011). The CAGG haplotype in the Miao population was a protective factor against hypertension (OR = 0.555, 95%CI: 0.330-0.934, P = 0.025). The rs3918188, rs1808593, and rs7830 in the Miao population showed an interaction effect on hypertension (P < 0.001). The rs11771443, rs3918188, and rs7830 in the Buyi and Han populations showed an interaction effect on hypertension (P = 0.013 and P < 0.001). The single nucleotide polymorphisms rs1808593 and rs7830 of NOS3 gene are associated with essential hypertension in Guizhou ethnic populations.

Association of eNOS gene 4a/4b VNTR and T786C polymorphism with Crimean-Congo hemorrhagic fever

The most common viral hemorrhagic fever is Crimean-Congo hemorrhagic fever (CCHF). Endothelial nitric oxide synthase (eNOS) gene polymorphisms have been linked to both hemorrhagic fevers and viral diseases. The study’s goal is to evaluate if the eNOS gene 4a/4b and T786C polymorphisms are related to CCHF. The study included 54 CCHF RNA-positive patients and 60 control subjects. The Bosphore CCHF virus Quantification Kit v1 was used to obtain CCHF RNA, and the Magnesia 16 isolation device was used to isolate DNA (Anatolia Gene works, Turkey). Polymerase chain reaction and restriction fragment length polymorphism were used to genotype the samples. The frequency of the eNOS 4a/4a, 4a/4b, and 4 b/4b genotypes in patients and the control was 6.6% versus 1.7%, 37.0% versus 43.3%, and 57.4% versus 55%, respectively. 4a: 24.07% of patients and 23.33% of controls; and 4 b: 75.92% of patients and 76.66% of controls. The frequency of the eNOS-786 T/C, T/T, T/C, and C/C genotypes in patients and the control group was 35.2% versus 68.3%; 51.9% versus 26.73%; and 13.0% versus 5.0%, respectively. The allele and genotype frequencies of the eNOS T786C variant differ statistically between patients and the control (p < 0.05). The eNOS T786C variant could be a genetic determinant for susceptibility to CCHF. To our knowledge, this is the first study to figure out the association between eNOS gene T786C polymorphisms and CCHF disease.

Endothelial nitric oxide synthase gene polymorphism (786T/C) in childhood acute lymphoblastic leukemia survivors

Objectives to detect eNOS gene polymorphism and its relation to cardiovascular complications in pediatric acute lymphoblastic leukemia (ALL) survivors. Methods CBC, renal and liver function tests, lipid profile, Carotid artery Intima Media Thickness (CIMT) and Brachial artery Intima Media Thickness (BIMT). eNOS gene polymorphism were done in 40 childhood ALL survivors and 40 controls. Results there was no significant difference between survivors and control groups regarding 786T/C polymorphism. There was significant increase in serum Cholesterol, TGs, LDL, VLDL and HbA1c in the TC and CC group more than the TT group while there was significant decrease in serum HDL in the TC and CC group more than the TT group. There was no significant difference as regards echocardiography findings between different polymorphism of 786T/C but there was a significant difference between 786T/C groups as regard to the carotid and brachial arteries intima media thickness (IMT) measurements being significantly higher in the TC and CC group more than the TT group. Conclusion : Carotid and brachial arteries intima media thickness measurements were higher in the survivors when compared to healthy controls. eNOS gene polymorphism may play a role in modifying or developing CVD in pediatric ALL survivors.

Patients with Invasive Tumors and eNOS Gene Polymorphisms with Subarachnoid Hemorrhage Tend to Have Poorer Prognosis.

Context Endothelial nitric oxide synthase ( eNOS) gene polymorphisms are found to predict predisposition to aneurysmal rupture and development of vasospasm in a patient of subarachnoid hemorrhage (SAH). eNOS gene polymorphisms are also found to predict invasiveness of malignant cells. Studies are not available in literature to describe the effect of eNOS gene polymorphisms and correlation between aneurysm and carcinoma. This study aims to investigate whether positive cancer history influences clinical outcome following SAH and eNOS gene polymorphisms. Materials and Methods The eNOS gene polymorphisms were analyzed in seven consecutive patients (mean age, 52.28 ± 20 years) with a diagnosis of invasive systemic tumors from 2011 to 2017. The eNOS 4a/4b eNOS -786T> eNOS 894G > T polymorphisms of the eNOS gene were determined by polymerase chain reaction and restriction fragment length polymorphism. Results Seven patients of aneurysmal SAH in association with malignancies were studied for eNOS polymorphisms expression and outcome. Three patients had carcinoma cervix: one patient of carcinoma breast and one each of transitional cell carcinoma of urinary bladder, spindle cell carcinoma of left kidney, and untreated patient of atypical pituitary (adenoma). A genotype study of eNOS gene polymorphisms in these patients shows common polymorphisms are involved in the determination of disease progression in malignancies and aneurysmal SAH. Conclusion Patients who expressed 4ab, eNOS -786T > TT/CC/TC, eNOS 894G > T GG/GT polymorphisms did better than patients who expressed only 4bb, though both were associated with poor prognosis.

Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms with Coronary Artery Disease in North Indian Punjabi Population.

Nitric oxide (NO) a potent vasodilator synthesized by endothelial cells has anti-atherosclerotic properties and maintains vascular tone. It has been documented that its reduced bioavailability in vascular endothelium plays an important role in the development and progression of coronary artery disease (CAD). Therefore, we aimed to investigate the association of -786T > C and 894G > T polymorphisms of eNOS with CAD. This study included 211 CAD patients and 260 controls of North Indian Punjabi population. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis revealed that the TC and CC genotypes of -786T > C were significantly associated with the higher risk of CAD (OR: 2.00, p = 0.001: OR: 4.63, p = 0.001, respectively). Similarly, the GT and TT genotypes of 894G > T were found to be significantly associated with the higher risk of CAD (OR: 1.96, p = 0.001; OR: 4.54, p = 0.005, respectively). Moreover, the recessive model in -786T > C (OR: 3.58, p = 0.002) and 894G > T (OR: 3.62, p = 0.009) polymorphisms provided 3.6-fold increased risk for CAD. Furthermore, the CG, TT, and CT haplotypes were also associated with the increased risk of CAD (OR: 2.1, p = 0.001; OR: 2, p = 0.002; OR: 3.1, p = 0.001, respectively). In addition, the CC genotype of -786T > C and GT genotype of 894G > T were significantly associated with higher levels of triglycerides (TG) and very low-density lipoproteins cholesterol (VLDL-C). The present study reported the association of -786T > C and 894G > T polymorphisms of eNOS with CAD and abnormal lipid levels in North Indian Punjabi population.

Endothelial Nitric Oxide Synthase Gene Polymorphisms Increase Risk of Deep Vein Thrombosis by Altering Homocysteine Levels.

Deep Vein Thrombosis (DVT) is a multicausal disease involving both acquired as well as genetic factors. Nitric oxide is an influential endogenous factor having its role in the development of deep vein thrombosis. It maintains the vascular integrity and any alterations in its levels may lead to a thrombotic event. It may also modulate homocysteine metabolism to cause hyperhomocysteinemia, which is a prominent risk factor for thrombosis. The objective of the study was to study if endothelial nitric oxide gene polymorphisms, 894G/T, and 2479G/A alter the plasma nitric oxide and homocysteine levels which may eventually increase the risk of deep vein thrombosis. One hundred Doppler ultrasonography and computerized tomography confirmed (for cerebral venous thrombosis), non-related DVT patients (M:F = 58:42; age range = 18 to 61 years) served as the study population. Two hundred hospital staff and their relatives or unrelated attendants of the patients served as the controls. Nitric oxide levels were determined by measuring its metabolites (NOx), and EIA was used to measure homocysteine levels. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for detecting the eNOS polymorphisms 894G/T and 2479G/A. In total, DVT subjects have 25% higher plasma levels of homocysteine and 37% lower levels of NOx in their circulation when compared to controls. In tertile analysis of nitric oxide and homocysteine levels, 894G/T and 2479G/A polymorphisms were associated with plasma nitric oxide and homocysteine levels. The increased risk of deep vein thrombosis was associated with endothelial nitric oxide gene polymorphisms and nitric oxide levels, but homocysteine levels were not a risk for deep vein thrombosis. The present study demonstrates that 894G/T and 2479G/A polymorphisms interact with lower levels of nitric oxide and higher levels of homocysteine that may possess the risk of deep vein thrombosis.

Evaluation of Endothelial Nitric Oxide Synthase Gene Polymorphism (T-786 C) in Patients with Slow Coronary Flow

Giriş ve Amaç: Yavaş koroner akım (YKA), koroner anjiyografide tıkayıcı lezyon yokluğunda koroner arterlerde opak maddenin gecikmesiyle karakterizedir. Patofizyolojik mekanizmaları belirsizdir. YKA için çeşitli hipotezler sürülmüştür; aterosklerozun erken fazının bir formu, mikrovasküler disfoksiyon, inflamasyon, vazokonstriktör ve vazodilatör faktörler arasındaki dengesizlik ve tromobist fonksiyon bozukluğudur. Endotelyal nitrik oksit sentaz (eNOS) geni T-786C polimorfizminin birçok damarsal hastalıkla ilişkisi bildirilmiştir. Bu çalışmanın amacı YKA ile eNOS gen T-786C polimorfizmi arasındaki ilişkiyi araştırmaktır.&#x0D; Gereç ve Yöntemler: Koroner arterleri normal ancak YKA olan 40 hasta (ortalama yaş 52 ± 9 yıl), koroner arter hastalığı (KAH) olan 35 hasta (ortalama yaş 55 ± 9 yıl) ve koroner anjiyografisi normal olan 30 hasta (ortalama yaş 51 ± 8 yıl) çalışmaya alındı. Sol ön inen arterde, TIMI kare sayısı 40 ve üzeri olması YKA olarak kabul edildi. eNOS geni T-786C polimorfizmleri polimeraz zincir reaksiyonu ile analiz edildi. Çalışma gruplarının demografik özellikleri ve ateroskleroz için major risk faktörleri değerlendirildi. YKA ve KAH ciddiyeti etkilenen damar sayısına göre değerlendirildi.&#x0D; Bulgular: Gruplar arasında yaş ve cinsiyet açısından anlamlı fark yoktu. Sigara içme yüzdesi, KAH grubunda diğer gruplardan daha yüksekti. Gruplar arasında genotip dağılımında istatiksel olarak anlamlı fark yoktu. YKA grubunda genotip dağılımı; TT genotip sıklığı 25 (%62,5), TC genotip sıklığı 12 (%30) ve CC genotip sıklığı 3’tü (%7,5). KAH grubunda genotip dağılımı; TT genotip sıklığı 16 (%45,7), TC genotip sıklığı 16 (%45,7) ve CC genotip sıklığı 3’tü (%8,5). Kontrol grubunda genetip dağılımı; TT genotip sıklığı 17 (%56,6), TC genotip sıklığı 10 (%33,3) ve CC genotip sıklığı 3’tü (%10). Dominat ve resesif modellerin istatiksel analizinde gruplar arasında anlamlı bir fark yoktu.&#x0D; Sonuç: Bulgularımız eNOS gen T-786C polimorfizmi ile YKA arasında anlamı bir ilişki olmadığını göstermektedir.

Effect of endothelial nitric oxide synthase gene polymorphism on cardiovascular death and nonfatal myocardial infarction in Japanese general population

Abstract Introduction Single nucleotide polymorphisms (SNP) of endothelial nitric oxide synthase (NOS3) have been reported to be associated with diabetes mellitus and myocardial infarction. However, few reports have prospectively investigated the effects of NOS3 SNP on cardiovascular death and nonfatal myocardial infarction. Purpose The purpose of this study was to investigate the impact of NOS3 SNP on cardiovascular death and the development of nonfatal myocardial infarction. Methods This prospective cohort study included 2,752 subjects (aged ≥40) who participated in a community based health checkup. We genotyped two SNPs within NOS3 (rs1808593, rs1799983). All subjects were prospectively followed during the median follow-up period of 15.4 years with the end point of cardiovascular death and nonfatal myocardial infarction. Results The homozygous G-allele (GG), heterozygous (GT), and homozygous T-allele (TT) carriers of rs1808593 were identified in 60 (2%), 706 (26%), and 1,986 (72%) subjects, respectively. Kaplan-Meier analysis demonstrated that homozygous G-allele carriers of rs1808593 had the greater risk than those without. Multivariate Cox proportional hazard regression analysis revealed that the homozygous G allele of rs1808593 was associated with cardiovascular death and the development of nonfatal myocardial infarction after adjusting for confounding risk factors. Conclusions NOS3 gene polymorphism could be a genetic risk factor for cardiovascular death and nonfatal myocardial infarction in the Japanese general population. Funding Acknowledgement Type of funding sources: None. Figure 1

Асоціація окремих показників ендотеліальної функції з T894G поліморфізмом гена ендотеліальної синтази монооксиду азоту у хворих на гіпотиреоз і супутній хронічний холецистит

Досліджено асоціацію T894G поліморфізму гена eNOS з окремими показниками ендотеліальної функції у хворих на гіпотиреоз і супутній хронічний некалькульозний холецистит. У пацієнтів із Т-алеллю відзначено вірогідне зростання на 33,1 % (P = 0,01) кількості десквамованих ендотеліоцитів у крові порівняно з такою в обстежених носіїв GG-генотипу. Також встановлено на 10,4 % (P = 0,04) вищу концентрацію загальних стабільних метаболітів монооксиду азоту та на 10,8 % (P = 0,02) більший рівень нітрат-аніонів у крові щодо групи порівняння. У хворих на гіпотиреоз із супутнім хронічним холециститом вміст судинного ендотеліального фактора росту в носіїв T-алелі на 27,7 % (P = 0,03) переважав такий у пацієнтів із GG-генотипом.

Endothelial Nitric Oxide Synthase Gene Polymorphism (T786C) among Sudanese Sickle Cell Disease Patients : Disease Prognostics and Response to Hydroxyurea

Endothelial Nitric Oxide Synthase Gene Polymorphism (T786C) among Sudanese Sickle Cell Disease Patients : Disease Prognostics and Response to Hydroxyurea