eNOS G894T Research Articles

Features of prooxidant/antioxidant balance disorders in patients with diabetic nephropathy — carriers of different genotypes of G894T polymorphism of eNOS gene

Objective — to determinate the state of prooxidant‑antioxidant balance in patients with type 2 diabetes mellitus with nephropathy — carriers of different genotypes of G894T (rs 1799983) polymorphism of eNOS gene. Materials and methods. 126 patients with diabetic nephropathy (DN) were examined. The control group included 20 healthy individuals. Patients with type 2 diabetes mellitus (DM) were divided into two groups depending on the eNOS rs 1799983 gene polymorphism: group I — patients with DN and G/G genotype eNOS G894T gene (n=80); group II — patients with DN and G/T and T/T genotypes eNOS G894T gene (n=46). Results. The distribution of genotypes of the rs1799983 polymorphism of the eNOS gene corresponded to the Hardy‑Weinberg equilibrium. Data analysis demonstrated a significant difference in the frequency of occurrence of genotypes and alleles of the studied polymorphism in the group of patients with DN compared with controls, which corresponds to the dominant model of inheritance (odds ratio 0.31 (95% confidence interval 0.09—0.99), p=0.045). There were significant gender differences in the frequency of genotypes and alleles of the studied polymorphism in the group of patients with type 2 DM with DN: women had a significantly lower risk of the G/T polymorphism genotype than men. The study of total antioxidant activity (TAA) revealed significantly lower values of this parameter in patients with G/G genotype of the rs1799983 polymorphism of the eNOS gene compared to carriers of the T allele (G/T+T/T genotypes). In diabetic patients with different genotypes of the rs1799983 polymorphism of the eNOS gene, the levels of total hydroperoxides (THP) did not differ significantly. Homozygous and heterozygous carriers of the T allele of the rs1799983 polymorphism of the eNOS gene had a significant increase in the prooxidant‑antioxidant balance. Conclusions. In patients with DN, the distribution of genotypes of the G894T polymorphism (rs 1799983) of the eNOS gene corresponds to the Hardy‑Weinberg equilibrium in all studied groups and does not differ significantly from European populations. In men, the risk of having a heterozygous G/T genotype of the G894T (rs 1799983) polymorphism of the eNOS gene is 3 times higher than in women (according to the dominant model of inheritance, odds ratio 0.41 (95% confidence interval 0.20—0.83), p=0.013). In carriers of G/T and T/T genotypes, a significant increase in prooxidant‑antioxidant balance was observed against the background of a decrease in total antioxidant activity, compared with carriers of G/G genotype (p<0.05).

Genetic polymorphisms associated with preeclampsia risk in Nigerian women

BackgroundPreeclampsia, a complex hypertensive disorder unique to pregnancy, significantly impacts maternal and fetal health worldwide, with a prevalence of 2–8%. This condition results from a complex interplay of genetic, environmental, and immunological factors.Aim and objectivesThis study aims to investigate the genetic predispositions to preeclampsia, focusing on specific gene polymorphisms among pregnant women at Central Hospital Auchi, Nigeria.Materials and methodsWe examined the endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), angiotensin-converting enzyme (ACE), and tumor necrosis factor-alpha (TNF-α) genes in 200 pregnant women, equally divided between preeclamptic patients and normotensive controls.ResultsThe eNOS G894T polymorphism was significantly associated with preeclampsia, with the T allele nearly doubling the risk. The VEGF C936T polymorphism's T allele also indicated a higher risk. The D allele in the ACE gene's insertion/deletion (I/D) polymorphism significantly increased the risk, as did the A allele in the TNF-α G308A polymorphism.ConclusionsThese findings highlight the importance of genetic factors in preeclampsia and suggest that genetic screening could improve risk stratification and early detection. Future research should integrate genetic, epigenetic, and environmental data to understand preeclampsia's multifaceted nature and develop targeted therapies. This study underscores the potential of personalized medicine in managing and reducing the risks associated with preeclampsia.

Investigation of the relationships between eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations and prostate cancer development and progression

BackgroundThis study aimed to investigate the relationships between eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations and prostate cancer development and progression. Materials and methodsThis study included 88 patients diagnosed with prostate cancer and 91 healthy controls. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were used to determine the genotype distributions of eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations. ResultsIn our study, the CC homozygous genotype of eNOS T786C gene variation was determined to be significantly higher in the prostate cancer patient group compared to the healthy control group (OR: 2.343, 95%Cl: 0.990–5.544, p = 0.026), while the CT heterozygous genotype was found to be significantly higher in the healthy control group compared to the prostate cancer patient group was found to be significantly higher (OR: 0.589, 95%Cl: 0.325–1.068, p = 0.041). In addition, while the TT homozygous genotype of the eNOS G894T gene variation was found to be significantly higher in the prostate cancer patient group compared to the healthy control group (OR: 9.068, 95%Cl: 4.396–18.777, p < 0.001), the GT heterozygous genotype was found to be significantly higher in the healthy control group compared to the prostate cancer patient group was determined significantly higher (OR: 0.227, 95%Cl: 0.121–0.427, p < 0.001). For eNOS (4VNTR (4a/b) - G894T) gene variations, aa-TT (p = 0.042) and bb-TT (p < 0.001) haplotype frequencies were significantly higher in the prostate cancer patient group, while aa-GT (p = 0.017), bb-GG (p = 0.049) and bb-GT (p < 0.001) haplotype frequencies were found to be significantly higher in the healthy control group. For eNOS (4VNTR (4a/b) - T786C) gene variations, the bb-CC haplotype frequency was determined to be significantly higher in the patient group (p = 0.049), while the bb-CT haplotype frequency was determined to be significantly higher in the control group (p = 0.008). For eNOS (T786C -G894T) gene variations, TT-TT (p < 0.001) and CC-TT (p = 0.025) haplotype frequencies were found to be significantly higher in the patient group. On the other hand, TT-GT (p = 0.002) and CT-GT (p < 0.001) haplotype frequencies were determined to be significantly higher in the control group. The aa genotype of the intron 4 VNTR (4a/b) gene variation was determined to be significantly higher at Gleason score ≥7 compared to Gleason score <7 (OR: 0.184, 95%Cl: 0.050–0.677, p = 0.005). PSA levels were determined significantly higher in patients with Gleason score 7 and above (p = 0.008). The risk of developing prostate cancer was found to be significantly higher in patients carrying the CC homozygous mutant genotype of the eNOS T786C gene variation (p = 0.024) and in patients carrying the TT homozygous genotype of the G894T gene variation (p = 0.021). ConclusionsIn our study, the CC homozygous genotype of the eNOS T786C gene variation was determined as a genetic risk factor for the development of prostate cancer, while the CT heterozygous genotype was determined as a protective factor against prostate cancer. For the eNOS G894T gene variation, the TT homozygous genotype was determined as a genetic risk factor for the development of prostate cancer, while the GT heterozygous genotype was determined as a protective factor against prostate cancer. Additionally, for eNOS (4VNTR (4a/b) - G894T) gene variations, aa-TT and bb-TT haplotypes have been identified as genetic risk factors for the development of prostate cancer, while aa-GT, bb-GG and bb-GT haplotypes have been identified as protective factors against the disease has been determined. For eNOS (4VNTR (4a/b) - T786C) gene variations, the bb-CC haplotype was determined as a genetic risk factor in the development of prostate cancer, while the bb-CT haplotype was determined as a protective factor against the disease. TT-TT and CC-TT haplotypes for eNOS (T786C -G894T) gene variations have been identified as genetic risk factors for the development of prostate cancer. In contrast, TT-GT and CT-GT haplotypes were found to be protective factors against the disease. The aa genotype of the intron 4 VNTR (4a/b) gene variation has also been identified as an important genetic risk factor in prostate cancer progression. Significantly increased PSA levels in patients with Gleason score 7 and above, and significantly increased PSA levels in patients carrying the CC and TT homozygous mutant genotype for T786C and G894T gene variations were determined as important risk factors. It is thought that the genetic biomarkers in our study may play a role as personalized therapeutic agents in slowing down the development of prostate cancer, increasing the effectiveness of treatment in prostate cancer, affecting the responses to drugs that regulate NO signaling, predetermining genetic predisposition to prostate cancer, and risk assessment in patients with prostate cancer.

The association of rs4646994 ACE and rs1799983 eNOS gene polymorphisms with metabolic effects of dapagliflozin in patients with diabetic nephropathy and essential hypertension

Objective — to establish possible associations of rs4646994 ACE and rs1799983 eNOS gene polymorphisms with metabolic effects of dapagliflozin in patients (pts) with diabetic nephropathy (DN) and essential hypertension (EH).&#x0D; Materials and methods. Clinical investigation and examinations involved 171 pts, from them 85 (49.7%) females and 86 (50.3%) males with DN of I—IV stages and EH of II—III stages, aged 31 to 82 years old (an average age was 59.38±1.58 years). They were also genotyped for rs4646994 (I/D) ACE and for rs1799983 (G894T) eNOS gene polymorphisms with the use of polymerase chain reaction. Among the patients with I/D polymorphism of ACE gene there were 24 (14.0%) pts with genotype II, 32 (18.7%) pts with genotype ID and 26 (15.2%) subjects with genotype DD. Among the participants with G894T eNOS gene polymorphism GG genotype was revealed in 29 (16.9%) pts, GT genotype was found in 33 (19.3%) cases and 27 (15.8%) examined persons had TT genotype. Standard parameters of lipid profile were measured in all included pts with a use of an immune enzyme method. Glucose oxidase and immune enzyme methods were used to define serum glucose and insulin levels; level of glycosylated hemoglobin (HbA1C) was detected by fluid chromatography method. Insulin resistance (IR) indices such as HOMA‑IR, triglyceride‑glucose index (TGGI), METS‑IR (metabolic score for insulin resistance) index were calculated by known formulas. Cardiometabolic risk (CMR) of the pts was estimated by ­METS‑IR index. Body mass index (BMI), body fat percentage (BFP), total fat mass (TFM) and fat mass index (FMI) in all the pts were calculated by standard known formulas. Serum uric acid concentration was measured with phosphovolframic method. Dapagliflozin 10 mg/daily was added for 24 weeks to the basic standard antidiabetic therapy including gliclazide or glimepiride and metformin combined with lipid lowering therapy containing atorvastatin. The standard therapy was not changed during the whole period of observation.&#x0D; Results. No association has been revealed between I/D ACE and G894T eNOS gene polymorphisms in pts with DN and EH, with a noted improvement of lipid blood spectrum due to administration of dapagliflozin in a dose of 10 mg/daily for 24 weeks. It has been established that allele D was associated with a reduction of dapagliflozin efficacy in the correction of carbohydrate metabolism disorders in pts with DN and EH. At presence of allele D (ID and DD) in genotype, the levels of glycemia, insulinemia, HbA1C, IR indices such as HOMA‑IR, TGGI, METS‑IR decreased less effective than in the case of allele D absence (genotype II). In pts with DN and EH who had G894T eNOS gene polymorphism, dapagliflozin 10 mg/daily improved muscle sensitivity to insulin and decreased CMR depended on genotype in the following order: GT &gt;TT &gt;GG, whereas the intensity of glycemia, insulinemia, HbA1C and HOMA‑IR index reduction was found to be associated with genotype as follows: GG &gt;GT &gt;TT. Allele I compared with allele D of I/D ACE gene polymorphism in pts with DN and EH was revealed to be associated with more significant reduction of BFP, TFM and FMI due to dapagliflozin administration. In pts with DN and EH who had G894T eNOS gene polymorphism dapagliflozin 10 mg/daily reduced a body mass due to its influence on fat accumulation but not on muscle tissue both in phenotype of visceral obesity (genotype GG) and in phenotype of sarcopenic obesity (genotype GT). In the realization of hypouricemic effects of dapagliflozin in patients with DN and EH, both genetic factors (D and T alleles of I/D ACE and G894T eNOS gene polymorphisms correspondingly), and metabolic factors (initial levels of HbA1C and UA together with anthropometric parameters characterized visceral obesity phenotype such as BMI, TFM and FMI) were involved.&#x0D; Conclusions. In pts with DN and EH, the association of I/D ACE (rs4646994) and G894T eNOS (rs1799983) gene polymorphisms with metabolic effects of dapagliflozin 10 mg/daily has been established. A presence of allele D of I/D ACE and allele T of G894T eNOS gene polymorphisms in genotype was concluded to be associated with less significant metabolic effects of dapagliflozin compared with an absence of these alleles in genotype.&#x0D;

The relationship between polymorphic variants of the endothelial NO-synthase gene and the course of diabetic nephropathy in patients with type 2 diabetes mellitus

Objective — to identify a possible association between the endothelial nitric oxide synthase (eNOS) gene G894T (rs1799983) polymorphism and the markers of renal function and glucose metabolism in patients with type 2 diabetes mellitus (DM2) with diabetic nephropathy (DN).&#x0D; Materials and methods. Examinations 126 patients with diabetic nephropathy (DN). The control group included 20 healthy individuals. Patients with DM2 were divided into two groups depending on the eNOS rs1799983 gene polymorphism: group I — patients with DN and G/G genotype eNOS G894T gene (n=80); group II — patients with DN and G/T and T/T genotypes eNOS G894T gene (n=46). Genotyping of the of the eNOS rs1799983 gene polymorphism was performed by the Taq‑Man® Fast Universal PCR Master Mix (Applied Biosystems, USA) and TaqMan® SNP Assay (Applied Biosystems, USA).&#x0D; Results. It has been established that in patients with DN, the distribution of genotypes of the G894T polymorphism of the eNOS gene corresponded to the Hardy‑Weinberg equilibrium in all groups and does not differ significantly from European populations. In diabetic patients with DN the 3 times higher total frequency of G/T and T/T genotypes eNOS G894T gene was established when compared to the control group. These findings prove the undoubted influence of the T allele on the development of DN in this group of patients. DN patients with genotypes G/T and T/T had significantly higher blood glucose and HOMA index (p &lt;0.05) than G homozygotes (genotype G/G). Patients with DN and G/G genotype eNOS G894T gene had better glomerular filtration rate and lower albuminuria compared to patients with G/T and T/T genotypes (p &lt;0.05).&#x0D; Conclusions. The establishing of association of eNOS gene polymorphism with the disease and further assessment of individual genetic risk is important for the development of a differentiated approach to the prevention and treatment of DN in patients with DM2 depending on the hereditary predisposition of an individual patient. Therefore, currently one of the most progressive approaches is to develop a strategy for early diagnosis, prognosis and preventive therapy of the disease using genetic markers.

Endothelial Nitric Oxide Synthase T-786C and G-894T Gene Polymorphisms: A Risk Assessment of Coronary Heart Disease.

The polymorphism of the endothelial nitric oxide synthase (eNOS) gene is thought to enhance the risk of coronary heart disease (CHD). The most protruding reason for endothelial dysfunction is the diminished production of NO. In the eNOS encoding gene, a number of mutations were associated with decreased NO effect promoting the presence of CHD. This study aims to look at the role of polymorphisms in the eNOS genes G-894T and T-786C in young South Indians. From January 2022 to May 2022, 91 angiographically proven CHD subjects attending the Department of Cardiology and Medicine and 91 controls from a master health checkup in the age group of 45 years participated in this observational cross-sectional study at SRM Medical College Hospital and Research Centre in Chennai, Tamil Nadu, India. Overnight fasting plasma samples were taken for analysis of the lipid profile as well as NO by Griess reaction utilizing an enzyme-linked immunosorbent assay (ELISA) technique. Polymerase chain reaction (PCR) and restricted fragment length polymorphism (RFLP) were used to amplify the T-786C and G-894T eNOS genes. When compared to controls, the mean level of serum NO in CHD patients was considerably lower. For eNOS T-786C polymorphism, the distribution of TC genotype (p = 0.017), odds (OD) ratio = 2.1, CC genotype (p = 0.011), OD ratio = 3.75, and minor C allele frequency (p = 0.001). And for eNOS G-894T polymorphism, the distribution of GT genotype (p = 0.01), TT genotype (p =0.02) with OD ratio and minor T allele frequency (p = 0.002) with OD ratio = 1.07 and 0.83. Our study concludes that the polymorphism of eNOS T-786C and G-894T genes may be the main causative association for the presence of CHD. How to cite this article: Jaishankar T, Shivasekar M, Vinodhini VM. Endothelial Nitric Oxide Synthase T-786C and G-894T Gene Polymorphisms: A Risk Assessment of Coronary Heart Disease. J Assoc Physicians India 2023;71(9):45-50.

Determination of the Roles of Endothelial Nitric Oxide Synthase 4VNTR (4a/b), G894T, T786C Gene Variations in the Bladder Cancer Development.

The aim of this study is to determine the roles of eNOS gene variations in BCA development. Our study included 91 patients diagnosed with BCA and 91 healthy controls. eNOS 4VNTR (4a/b), T786C and G894T gene variations genotype distributions were determined by PCR and RFLP methods. The significant difference was determined between these groups in terms of eNOS T786C and eNOS G894T gene variations genotype distributions (p < 0.05). TT genotype for G894T gene variation and CC genotype for T786C gene variation were detected higher in patients. The CC genotype of T786C gene variation was detected significantly higher in male patients than in male controls (p < 0.05). In addition, aa-TT, ab-TT, bb-TT haplotypes of 4VNTR (4a/b)-G894T gene variations, aa-CC, ab-CC, bb-CC haplotypes of 4VNTR (4a/b)-T786C gene variations and TT-TT, TT-CC, TT-CT, GG-CC, GT-CC haplotypes of G894T-T786C gene variations were observed in patient group more than control group. The significant difference was detected between these groups in terms of eNOS (G894T-T786C) haplotypes (p < 0.05). In our study, eNOS T786C and eNOS G894T gene variations were determined important genetic risk factor in the Thrace population of Turkey.

The role of eNOS gene polymorphisms on contrast induced nephropathy development in chronic kidney disease patients.

Contrast nephropathy is a result of contrast media given through intravascular routes. Nitric oxide gene polymorphisms may alter the hemodynamic stability resulting in medullary ischemia Nitric oxide gene polymorphisms may have an enhancing role in contrast media related renal injury. The aim of this study was to investigate the role of eNOS intron 4a/b, T786C, and G894T gene polymorphisms on contrast-nephropathy risk. Ninety-four chronic kidney disease patients with contrast nephropathy and 120 chronic kidney disease patients without contrast nephropathy were included. DNA isolation was performed and specific regions of DNA for eNOS G894T, T786C, and intron 4a/b genes were amplified by polymerase chain reaction technique. TT polymorphism of T786C gene and GG polymorphism of G894T gene were detected to be possibly protective from contrast induced nephropathy. Endothelial nitric oxide synthase G894T gene polymorphisms, older age, and presence of diabetes mellitus may influence contrast nephropathy development.

ENOS Gene Variants and Their Genetic Susceptibility Associated with Coronary Heart Disease

Objective: Gene variations in the gene encoding endothelial nitric oxide synthase (eNOS) may impact the initiation of coronary heart disease (CHD). Insufficient production of nitric oxide (NO) is the most obvious cause of endothelial dysfunction. The aim of this study was to investigate polymorphisms in the eNOS genes G894T and T786C that influence the development of CHD.Material and Methods: A total of 91 angiographically proven CHD subjects at the Department of Cardiology and Medicine and 91 controls at master health check, in the age group of 30-45 years were evaluated in this cross-sectional study. After overnight fasting blood samples were collected for evaluation of lipid profile by using Auto analyzer AU 480 and NO by Griess reaction, using Enzyme linked Immunosorbent assay. Polymerase Chain Reaction and Restriction Fragment Length Polymerization were used to amplify the eNOS gene, T786C, and G894T, respectively.Results: A significant decrease in the serum level of NO was observed in CHD subjects compared to controls. In eNOS T786C polymorphism, the distribution of TC genotype (p-value=0.017) odds ratio (OR)=2.1 and minor C allele frequency (p-value=0.001). Additionally, for eNOS G894T polymorphism, the distribution of GT genotype (p-value=0.014) OR=2.03 and minor T allele frequency (p-value=0.001).Conclusion: This study concludes that polymorphisms of the eNOS genes G894T and T786C could increase the risk of CHD.

Association of polymorphisms in genes encoding prothrombotic and cardiovascular risk factors with disease severity in COVID-19 patients: A pilot study.

The present study aimed to assess the association of 16 polymorphisms in genes encoding prothrombotic and cardiovascular risk factors with COVID‐19 disease severity: FV G1691A, FV H1299R, FII G20210A, MTHFR C677T, MTHFR A1298, factor XIII V34L, PAI‐1 4G/5G, EPCR haplotypes (A1/A2/A3), eNOS −786 T > C, eNOS G894T, LTA C804A, ACE I/D, ITGB3 PIA1/A2, ITGA2B Baka/b, β‐Fbg −455 G > A and ApoB R3500Q. The study included 30 patients with severe COVID‐19 and 49 non‐severe COVID‐19 patients. All studied polymorphisms except ITGA2B Baka/b were determined using multilocus genotyping assays CVD StripAssays (ViennaLab Diagnostics), while ITGA2B was genotyped using a real‐time PCR method based on TaqMan technology. A higher frequency of carriers of at least one ITGB3 PIA2 allele was found in severe COVID‐19 patients (p = 0.009). The distribution of genotypes was significantly different for ß‐Fbg −455 G > A (p = 0.042), with only three homozygous AA genotypes found among severe COVID‐19 patients. The association with an increased risk for severe COVID‐19 was found for ITGB3, with carriers of at least one ITGB3 PIA2 allele having a 3.5‐fold greater risk of severe COVID‐19 (p = 0.011). Genotype distribution differences were obtained for the combinations of FV H1299R and FXIII V34L (p = 0.026), ITGB3 PIA1/A2 and ITGA2B Baka/b (p = 0.024), and ACE I/D and PAI‐1 4G/5G (p = 0.046). ITGB3 polymorphism emerged as an independent risk factor for severe COVID‐19 and homozygosity for ß‐Fbg −455 G > A mutation could contribute to disease severity. The combined effect of polymorphisms in genes encoding prothrombotic and cardiovascular risk factors could further contribute to disease severity.

Endothelial nitric oxide synthase G894T, intron 4 VNTR, and T786C polymorphisms in retinopathy of prematurity

Our objective in this study was to assess the association between eNOS gene, that achieves synthesis of nitric oxide especially in the endothelial cells known to have an important role in angiogenesis and vasculogenesis, G894T, intron 4 VNTR (27-bp repeat) and T786C functional polymorphisms and retinopathy of prematurity (ROP), which is an important cause of morbidity in premature or low birth weight babies. A total of 139 babies who were followed up in our neonatal intensive care unit because of premature birth in our hospital or admitted to our unit. 69 of them had retinopathy of prematurity and comprised the patients group. The remaining 70 babies who did not have ROP comprised the control group. An additional of 1 ml of blood samples were drawn from babies who were in the study groups during routine laboratory analysis. eNOS gene polymorphisms were determined by using polymerase chain reaction method. eNOS G894T, intron 4 VNTR and T786C gene polymorphisms did not differ between the patient and control groups (p > 0.05). Using logistic regression analysis; while gender did not differ between two groups; gestational age, birth weight, time on mechanical ventilation differ between two groups. After adjustment for variables other than eNOS gene polymorphisms, we found no significant difference in the genotype distribution of eNOS G894T, intron 4 VNTR and T786C polymorphisms (p > 0.05). We observed no association between ROP and eNOS gene polymorphisms but needs more investigation.

Investigation of eNOS G894T Gene Polymorphism in Patients with Pseudoexfoliation Syndrome: A Preliminary Study.

Objectives:The aim of this study is to investigate the relationship between pseudoexfoliation syndrome (XFS) and pseudoexfoliative glaucoma (XFG) and endothelial nitric oxide synthase (eNOS) G894T polymorphism.Methods:Seventy-eight eyes of 78 patients who had undergone uncomplicated cataract surgeries for senile cataract were included in this study. Forty patients with XFS were included in the study group, and 38 patients without XFS constituted the control group. Patients with XFS were divided into two subgroups according to their XFG development, and subgroup analysis was performed. Venous blood samples were taken from all patients before surgery and 894 G>T (rs1799983) polymorphism on the eNOS gene was evaluated by RT-PCR.Results:While the mean age in the control group was 65.97±10.64 years (23 males and 15 females), the mean age in the study group was 73.05±6.79 years (30 males and 10 females), (p<0.001). Regression analysis of the risks caused by the genotype and alleles between the control and study groups revealed that the homozygous alleles were more common in the study group, and heterozygous or mutant alleles have reduced the development of XFS approximately 2-folds. However, this was not statistically significant (p=0.11). Similarly, when subgroup analysis was performed, it was found that there was no significant relationship between XFG in patients with XFS and gene polymorphism.Conclusion:In this study, it was observed that there was no relationship between the G894T polymorphism in the eNOS gene and the development of XFS/XFG.

Endothelial Nitric Oxide Synthase 4a/B Polymorphism and Its Interaction with Enos G894T Variants in Type 2 Diabetic Patients: Modifying the Risk of Diabetic Nephropathy.

The article's abstract is not available.

The association of T786C and G894T polymorphisms of eNOS gene with diabetic retinopathy in Greece.

To investigate whether eNOS T786C (rs2070744) and G894T (rs1799983) gene polymorphisms are associated with diabetic retinopathy in Greek diabetic patients. 271 patients with type-2 diabetes mellitus participated in our study; 130 suffered from diabetic retinopathy and 141 not. All the patients underwent a complete ophthalmological examination, while clinical and demographic data were assessed. Furthermore, they were genotyped for rs2070744 and rs1799983 single nucleotide polymorphisms of eNOS gene. Regarding the clinical and demographic data, no significant differences were detected between the studied groups, except for hemoglobin A1c levels and the frequency of insulin treatment (higher in patients with diabetic retinopathy). The frequency of rs1799983 GT genotype was significantly elevated in patients with diabetic retinopathy (55% vs. 40%, P = 0.011) and was associated with a 2-fold increased risk of developing retinopathy (OR 1.92, 95% CI 1.16-3.17). Furthermore, we demonstrated that the aforementioned genotype was significantly and independently associated with increased odds for retinopathy onset in diabetic subjects (OR 2.23, 95% CI 1.28-3.90, P = 0.005), regardless of the impact of other confounders. We documented that rs1799983 GT genotype could be recognized as an independent risk factor of retinopathy in Greek patients with type-2 diabetes mellitus, while no role for rs2070744 polymorphism was identified. Further research in different ethnic groups will clarify the exact association of these polymorphisms with the risk for diabetic retinopathy development.

Endothelial nitric oxide synthase polymorphism and venous thromboembolism: A meta-analysis of 9 studies involving 3993 subjects.

Endothelial nitric oxide synthase (eNOS) polymorphism may influence the risk of venous thromboembolism (VTE). However, data from published studies with low statistical power are inconclusive. The present meta-analysis aimed to assess the relationship between eNOS polymorphism and the risk of VTE. Case-control studies evaluating the association between the eNOS polymorphism and VTE were searched in PubMed, Embase, Web of Science, Google Scholar, Wanfang, Chinese National Knowledge Infrastructure (CNKI), the Chongqing VIP Chinese Science and Technology Periodical Database (VIP), and Chinese Biomedical Literature Database (CBM). A total of 1588 cases and 2405 controls from 9 studies were included in the analysis. The results showed that eNOS G894T polymorphism was related to VTE susceptibility and the difference was statistically significant [T vs G: OR = 1.41, 95% CI (1.13, 1.75), P = 0.002; TT + GG vs TG: OR = 0.71, 95% CI (0.60, 0.84), P = 0.000; TT + TG vs GG: OR = 1.45, 95% CI (1.23, 1.70), P = 0.000]. Additionally, eNOS Intron 4 VNTR polymorphism was related to VTE susceptibility and the difference was statistically significant [4b4b vs 4a4a + 4a4b: OR = 2.77, 95% CI (1.01, 7.61), P = 0.048]. ENOS G894T and eNOS Intron 4 VNTR polymorphisms were associated with VTE susceptibility, especially in Asian populations. However, multicenter studies with larger samples should be conducted to further clarify this association and verify our findings.

Medication-related osteonecrosis of the jaw (MRONJ) and eNOS Polymorphisms in multiple myeloma patients: a single center experience

BackgroundMultiple myeloma (MM) constitutes approximately 10% of hematological malignancies. Bisphosphonates have established themselves in solid organ metastasis and multiple myeloma lytic bone lesions by inhibiting osteoclast activation. Medication-related osteonecrosis of the jaw (MRONJ) emerges as an important complication. Investigating host-based factors, and developing personal risk factors gain importance in the development mechanism of MRONJ. We aimed to reveal the different genotype polymorphisms, and clinical effects of eNOS in patients with a diagnosis of MRONJ in MM patients.MethodsMedical records and blood samples were collected from 60 MRONJ patients with MM and 60 healthy controls. Inclusion criteria was having an exposed maxillofacial bone for more than eight weeks, a history of bisphosphonates, and no history of radiation therapy for the jaws. eNOS G894T and intron 4 VNTR were calculated by polymerase chain reaction and/or restriction fragment length polymorphism.ResultseNOS G894T and VNTR genotypes and alleles were compared statistically with the healthy control group. There was no significant difference between the two groups. In comparison between G894T and clinical parameters, aphthous stomatitis was more common in TT genotype, while DMFT > 3 was more common in TG-GG genotype (p = 0.035, 0.023).ConclusionseNOS induces osteogenesis in bone metabolism, with its regulatory effects on bone remodeling and also NO induced angiogenesis takes place indirectly with its protective effect on endothelial functions. We see that these polymorphisms affecting the entire process of bone remodeling and angiogenesis, especially mucosal damage, which is the triggering factor of MRONJ pathology, have been revealed in the MM patient group. Considering the MRONJ initiating factors, it is necessary to emphasize the importance of our study results. It should be seen as an important step for new studies towards MRONJ and its treatment.

The role of caveolin-1 and endothelial nitric oxide synthase polymorphisms in susceptibility to prostate cancer.

Caveolin-1(cav-1) is overexpressed in prostate cancer (PC) and is associated with progression of the disease. We investigated the effects of CAV1-T29107A and endothelial nitric oxide synthase (eNOS) G894T polymorphisms on the serum levels of testosterone, NO and prostate-specific antigen (PSA) in patients with PC. We genotyped cav-1 and eNOS genes in 112 PC patients and 150 healthy controls by PCR-RFLP. Serum levels of and were measured using spectrophotometry, and serum levels of testosterone and PSA were measured by ELISA. The frequencies of CAV1 genotypes A/T vs. A/A according to the dominant model AT+TT vs. AA genotype and T allele were significantly higher in PC patients in comparison with the control group and considerably increased the risk of disease by 2.19-, 1.44- and 1.6-fold, respectively. AT+TT genotypes were associated significantly with the increased risk of PC in those with smoking or diabetes by 3.08-fold (P=.004). Individuals carrying concurrently the T allele of CAV1 A29107T and the T allele of eNOS G894T genes had a significantly increased risk of PC by 2.52-fold (P=.009). We did not find any significant relationship between eNOS G894T genotypes and alleles with susceptibility to PC. Our results highlighted the significance of CAV1-T29107A SNP but not (eNOS) G894T in the susceptibility to PC in our the population that we have studied.

Genetic associations of the origin and predictive estimation of the acute non-ST segment elevation myocardial infarction in patients with metabolic syndrome

Abstract Background and introduction Metabolic syndrome (MS) is a baseline condition that influencesthe management of patients with coronary heart disease (CHD). The assessment of genotyping characteristics in patients with MS with non-ST segment elevation myocardial infarction (nSTEMI) remains a challenge. Purpose To define characteristics of G Protein β3 subunit gene C825T polymorphism; T786C in the eNOS gene and G894T in the eNOS gene in patients with MS after nSTEMI, evaluate the prognostic specificity of genotypes in a study population. Methods The study included 150 patients with CHD and MS. The main group included 99 patients (69.7% males, a mean age of (67.4±0.7 y))with nSTEMI, preserved left ventricular systolic function who underwent urgent percutaneous coronary intervention. The control group included 51 patients with a mean age of (64.6±1.3 y) without the history of previous myocardial infarction and acute cerebrovascular disease. There was no statistically significant difference between gender and age in two groups (p&amp;gt;0.05). The predictive significance of the main group genotypes was estimated with odds ratio and risk ratio of “cumulative point of undesirable effects” (CPUE) and included: cardiovascular death, acute coronary syndrome, repeat revascularization, hospitalization for congestive heart failure. The accuracy of the genotype distribution corresponded to the Hardy-Weinberg equilibrium (p&amp;gt;0.05). The accuracy of the results was analyzed using Student, χ2, Fisher's criteria. Results We received high patient numbers with CC genotype of eNOS:786 gene in the main group (n=19 (19.2%)) as compared with the controls (n=3 (6.2%)) (p&amp;lt;0.05, φ=0.03), with GG genotype of eNOS:894 (p&amp;lt;0.01, χ2=8.0) in the main group (n=59 (59.6%)) as compared with the controls (n=18 (35.3%)), with CC genotype of eNOS:894 in the control group (n=40 (78.4%)) as compared with the main group (n=56 (56.6%)) (p&amp;lt;0.05; χ2=7.0). Patients who were heterozygous for eNOS:894 gene prevailed in the main group (n=30 (30.3%)) as compared with the controls (n=27 (52.9%)) (p&amp;lt;0.01, χ2=7.3). The statistically significant CPUE was more frequent diagnosed in patients with TT genotype of GNβ3:825 (OR=12.00, 95% confidence interval ((CI): 2.8–51.7, p&amp;lt;0.05), CC genotype of eNOS:786 (OR=5.1, 95% CI: 1.3–20.0, p&amp;lt;0.05) and TT genotype of eNOS:894 (OR=8.0, 95% CI: 1.8–35.2, p&amp;lt;0,05). Conclusions 4 practically applicable categories of reviewed genotypes were found: 1) nSTEMI - -protective: CC genotype for GNβ3:825 gene, GT – eNOS:894, 2) nSTEMI – unfavorable: CT–GNβ3:825, CC – eNOS:786 and GG – eNOS:894, 3) CPUE – unfavorable: TT – GNβ3:825, CC – eNOS:786, TT – eNOS:894, and 4) nSTEMI, CPUE-neutral: TT and TC – eNOs:786. CC – eNOS:786 genotype is separated as unfavorable for the development of both nSTEMI and CPUE. More studies are necessary for a personified approach, taken into account the obtained features of genetic associations. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Scientific Research Institute - S.V. Ochapovsky Clinic Regional Hospital #1, Krasnodar

Genetic association between eNOS gene polymorphisms and risk of carotid atherosclerosis : Ameta-analysis.

Endothelial nitric oxide synthase (eNOS) has been reported to be involved in the atherosclerotic process. Anumber of studies have investigated the association between eNOS gene polymorphisms and the risk of carotid atherosclerosis (CAS). However, the results are conflicting and inconclusive. The aim of this study was to evaluate precisely the association between the eNOS T786C, G894T, and 4a/4b polymorphisms and CAS risk. Ameta-analysis was carried out by retrieving relevant studies from PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Cochrane databases without arestriction on publication year. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of the association with CAS. Data were obtained from eight case-control studies comprising 2975cases and 2624 controls. Significant associations were detected between the allelic and recessive models of the eNOS T786C polymorphism (allelic: p = 0.04; OR, 95% CI = 1.57 [1.01, 2.44]; recessive: p = 0.03; OR, 95% CI = 1.53 [1.04, 2.24]), as well as the allelic and dominant models of the eNOS 4a/4b polymorphism, and CAS risk in an Asian subgroup (allelic: p = 0.02; OR, 95% CI = 1.49 [1.07, 2.07]; dominant: p = 0.01; OR, 95% CI = 1.50 [1.09, 2.05]), but not in aCaucasian subgroup (p > 0.05). No association was observed between the eNOS G894T polymorphism and CAS risk (p > 0.05). Our study provides evidence that the allelic and recessive models of the eNOS T786C polymorphism and the allelic and dominant models of the eNOS 4a/4b polymorphism may increase the risk of CAS in Asian populations.

A Relationship between Endothelial Nitric Oxide Synthetase Gene Variants and Substance Use Disorder.

Addictive substances are known to result in oxidative stress (OS). OS enhances the generation of free radicals and reactive oxygen species (ROS) and reduces antioxidant capacity. Peroxides and oxygen radicals, including hydrogen peroxide and superoxide and radical nitrogen species, including nitric oxide (NO), are parts of the ROS. Gene variants of the endothelial nitric oxide (eNOS) affect the plasma levels of NO. This study aimed to investigate whether there was an association between eNOS variants and substance use disorders (SUDs) risk in the Turkish population. Two eNOS variants (G894T and 27 bp VNTR 4b/a in intron 4) were examined in 216 SUD patients and 140 healthy controls. The eNOS variants were assessed with the PCR based on the RFLP analysis. Since the patient group consisted only of men, the control group was examined as a mixed and male-only. The eNOS G894T homozygous T/T genotype revealed a significant association with susceptibility to SUD. The patients carrying T/T genotype had SUD risk 1.054 times as much as the controls and male controls had (p=0.004 and p=0.038, respectively). eNOS 4a/4a genotype increased in patients as compared to male controls (p=0.048). The homozygous 4b/4b genotype was higher in the male control group than in SUD patients (p=0.029). eNOS VNTR 4a allele was more prevalent in the patients than in both controls and male controls (p=0.026 and p=0.0033, respectively). This study is one of the first studies investigating the relationship between two eNOS gene variants and SUD in our country. Our findings show that eNOS G894T and VNTR variants may be the significant risk factor for SUDs in Turkish subjects.