Endothelial Nitric Oxide Synthase T-786C Research Articles

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.

Investigation of the relationship between endothelial nitric oxide synthase T786C polymorphism and PSA, PSA derivatives, and prostate cancer in the Turkish population.

Prostate cancer is a slowly progressing cancer. However, it has remained a major medical problem for affected men. Risk factors of prostate cancer include age, race, and prostate cancer family history. Prostate cancer may occur at different frequencies between ethnic populations and countries. Currently, studies on genetic risk factors in prostate cancer aetiology have been increasing. Due to the importance of changes in endothelial nitric oxide synthase in carcinogenesis, we aimed to reveal whether eNOS T786C polymorphism is associated with prostate cancer. Archival samples included in this study were whole blood samples taken from patients who were grouped according to prostate biopsy pathology results (BPH, n: 42; PCa, n: 48) and from healthy participants (controls, n:27). DNA was isolated from these whole blood samples and real-time polymerase chain reaction analysis was performed for endothelial nitric oxide synthase T786C polymorphism with LightCycler 480 II. Measured free and total prostate-specific antigen serum levels were evaluated retrospectively. There was a statistical difference between patient-healthy control and control-healthy control groups regarding genotype distributions for eNOS T786C hism. Controls were more likely to have TC and CC genotypes and C alleles than the other two groups. Compared to other groups, the percentage of the eNOS786C allele in the control group was found to be higher. As a result of these data, it can be thought that carrying the allele may be protective against the disease.

The endothelial nitric oxide synthase T-786c mutation, a treatable etiology of Prinzmetal's angina

We assessed to what degree the endothelial nitric oxide synthase (eNOS) T-786C polymorphism, leading to reduced nitric oxide (NO) production-coronary artery spasm, was reversibly associated with Prinzmetal's variant angina (PVA). ENOS T-786C PCR analyses were done in 19 women, 8 men, 26 Caucasian, 1 African-American, median age 53, with well-documented PVA and in 72 healthy controls who did not differ by race or gender. Of the 27 cases, 7 (26%) were homozygous for wild-type normal eNOS (CC), 13 (48%) were T-786C heterozygotes (CT), and 7 (26%) were T-786C homozygotes (TT) vs controls, 44 (61%) CC, 27 (38%) TC, and 1 (1%) TT, P<0.0001. The mutant eNOS T-786C allele frequency in PVA patients was 27/54 (50%) vs 29/144 (20%) in controls, P < 0.0001. On oral L-arginine (9.2 g/d) to increase production of NO for a median of 4.7 months in 16 PVA patients with symptomatic angina despite conventional nitrate-calcium channel blockers, using the Seattle Angina Questionnaire, satisfaction with symptom remission rose (median) from 50% to 100% (P = 0.004), satisfaction with angina frequency reduction rose from 65% to 80% (P = 0.02), satisfaction with treatment for symptoms rose from 38% to 88% (P=0.001), and perception of overall life status rose from 25 to 71% (P = 0.0002). On L-arginine (median 4.7 months), in 20 patients, none had worsening of angina, and of 7 patients whose angina totally resolved, eNOS T-786C homozygosity was over-represented, P = 0 .04. The eNOS T-786C mutation appears to be a reversible etiology of PVA in patients whose angina may be ameliorated by L-arginine.

Polymorphism of endothelial nitric oxide synthase T786C in patients with normal tension glaucoma and primary open angle glaucoma

AbstractPurpose Comparison of allelic variant frequency of eNOS gene T786C in patients with normal tension glaucoma and primary open angle glaucoma.Methods The studied group constituted 97 patients with NTG and 49 patients with POAG. DNA was isolated from peripheral blood and T786C polymorphism was studied by RT‐PCR method.Results In NTG patients TT genotype was present in 36% patients, TC in 52.6% and CC in 11.3%. In POAG patients genotype TT was detected in 42.9% persons, TC in 48.9% and CC in 8.2%. The difference in allelic frequency was not statistically significant (p=0.75). In women with NTG the allelic frequency was similar to men (respectively, in women: TT‐35.9%, TC‐48.4%, CC‐15.6% and men TT‐36.4%, TC‐60.6%, CC‐3%; p=0.92). In group of women with POAG the allelic frequency was also similar to men (in women: TT‐41.2%, TC‐50%, CC‐8.8% and men: TT‐46.7%, TC‐46.7% a CC‐6.7%; p=0.09). Comparing the difference in genotype frequencies between both glaucoma types no significant difference was detected in women (p=0.9) and men (p=0.7). The CC genotype was most frequently present in NTG women (15.6%), comparing to NTG men (3%) and POAG women (8.8%).Conclusion The frequency of particular genotypes of T786C polymorphism of eNOS gene did not significantly differ in patients with NTG and POAG, yet the mutated allelic form is most frequent in NTG women.

Association of plasma nitric oxide concentration and endothelial nitric oxide synthase T-786C gene polymorphism in coronary artery disease

Nitric oxide (NO) is synthesized from l-arginine by endothelium nitric oxide synthase (NOS3) and plays important roles in many physiologic and pathologic processes. NO involved in the pathogenesis of coronary atherosclerosis. In the present study we hypothesized that polymorphisms of NOS gene might be associated with increased risk of coronary artery disease (CAD) and plasma NO concentrations. The eNOS gene polymorphism was investigated in 241 unrelated CAD patients with positive coronary angiograms and 261 ages matched control subjects without a history of symptomatic CAD. The NOS3 gene polymorphisms were analyzed by RFLP. Plasma NO, lipid profile and other risk factors were also assessed. The genotype frequencies for T-786C polymorphism differed significantly between CAD patients and controls (p=0.041). The mean plasma NOx concentrations showed significant differences according to genotypes of T-786C polymorphism in total population only. The mean plasma NOx increased in those individuals that are homozygote for C allele in promoter compared with those individuals are heterozygote for this allele and homozygote for T allele in total population and Controls, but no in CAD patients. The present study provides evidences that T-786C polymorphism of the NOS3 gene is associated with CAD. T-786C polymorphism was not associated with increased plasma NO in CAD patients.

Improved prediction of early-onset coronary artery disease using APOE ε4, BChE-K, PPARγ2 Pro12 and ENOS T-786C in a polygenic model

Objectives: Coronary artery disease (CAD) is often polygenic due to multiple mutations that contribute small effects to susceptibility. Since most prior studies only evaluated the contribution of single candidate genes, we therefore looked at a combination of genes in predicting early-onset CAD [apolipoprotein E ( APOE) ε4, butyrylcholinesterase ( BChE) K, peroxisome proliferator-activated receptor γ2 (PPARγ2) Pro12Ala and endothelial nitric oxide synthase ( ENOS) T-786C]. Design and methods: We examined the frequencies, individually and in combination, of all four alleles among patients with early-onset CAD ( n = 150; <50 years), late-onset CAD ( n = 150; >65 years) and healthy controls ( n = 150, age range 47–93 years). Differences in the proportion of subjects in each group with the given gene combination were assessed and likelihood ratios (LR) were calculated using logistic regression to combine the results of multiple genes. Results: Early-onset CAD patients had increased, but non-significant, frequencies of PPARγ2 Pro12/Pro12 ( P = 0.39) and ENOS T-786C ( P = 0.72), while BChE-K was only significantly higher in early-onset CAD patients compared to controls ( P = 0.03). There were significantly more APOE ε4 alleles alone ( P = 0.02) or in combination with BChE-K ( P = 0.02) among early-onset CAD patients compared to late-onset CAD ones or controls. When combined, there was a higher prevalence of all four alleles in early-onset CAD (early-onset CAD patients: 10.7%, late-onset CAD patients: 3.3% and controls: 2.7%, P = 0.01). LR for early-onset CAD for a single allele was relatively small (1.08 for PPARγ2 to 1.70 for APOE ε4). This increased to 2.78 (1.44–5.37) when combining all four alleles, therefore increasing the pre-test probability of CAD from 5% to a post-test probability of 12.7%. Conclusions: While any single mutation causes only a mildly increased LR (none > 1.7), in combination, the likelihood of early-onset CAD increased to 2.78 with four mutations. The genetics of early-onset CAD appear to be multifactorial, requiring polygenic models to elucidate risk.

Influence of endothelial nitric oxide synthase T-786C single nucleotide polymorphism on aneurysm size

Among patients with aneurysms, those with heterozygous (T/C) endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), a mutation reducing endothelial nitric oxide synthesis, are reported to have larger ruptured intracranial aneurysms (IAs) than those with homozygous (C/C or T/T) genotype. The authors tested patients harboring aneurysms for eNOS T-786C SNP in two populations--Japanese and Korean. The eNOS T-786C SNP was genotyped through direct sequencing in genomic DNA obtained from 336 Japanese and 191 Korean patients with lAs and 214 Japanese and 191 Korean control volunteers. Differences in genotype frequencies among the various aneurysm sizes were evaluated using the Fisher exact test. There was no significant difference in heterozygous (T/C) eNOS T-786C SNP between aneurysms 5 mm or smaller and those from 6 to 9 mm, and between lesions 5 mm or smaller and those 10 mm or larger in 336 Japanese patients harboring aneurysms--220 with ruptured and 116 with unruptured lesions--and in 191 Korean patients with ruptured aneurysms. The eNOS T-786C SNP genotype does not influence the size of aneurysms.