The role of ENOS polymorphism (C774T) in the progression of acute peritonitis and the formation of complications

In order to determine the role of ENOS (C774T) gene polymorphism in the progression of acute peritonitis and the formation of complications, a clinical and biochemical study of 40 patients with acute peritonitis was conducted. As a result of the study, it was proved that the early period of acute peritonitis is characterized by the development of endogenous intoxication, intensification of oxidative phenomena, hypercoagulation of the homeostasis system and inhibition of fibrinolysis, and in patients with acute peritonitis, carriers of the pathological TT genotype of the endothelial nitric oxide synthase gene, more pronounced deviations of homeostatic parameters are observed. Key words: acute peritonitis, genotype, DNA diagnostics, genetic testing of genotypes.

Recent Updates and Advances in Winiwarter-Buerger Disease (Thromboangiitis Obliterans): Biomolecular Mechanisms, Diagnostics and Clinical Consequences

Thromboangiitis obliterans (TAO) or Buerger’s disease is a segmental inflammatory, thrombotic occlusive peripheral vascular disease with unknown aetiology that usually involves the medium and small-sized vessels of young male smokers. Due to its unknown aetiology and similarities with atherosclerosis and vasculitis, TAO diagnosis is still challenging. We aimed to review the status of biomolecular and laboratory para-clinical markers in TAO compared to atherosclerosis and vasculitis. We reported that, although some biomarkers might be common in TAO, atherosclerosis, and vasculitis, each disease occurs through a different pathway and, to our knowledge, there is no specific and definitive marker for differentiating TAO from atherosclerosis or vasculitis. Our review highlighted that pro-inflammatory and cell-mediated immunity cytokines, IL-33, HMGB1, neopterin, MMPs, ICAM1, complement components, fibrinogen, oxidative stress, NO levels, eNOS polymorphism, adrenalin and noradrenalin, lead, cadmium, and homocysteine are common markers. Nitric oxide, MPV, TLRs, MDA, ox-LDL, sST2, antioxidant system, autoantibodies, and type of infection are differential markers, whereas platelet and leukocyte count, haemoglobin, lipid profile, CRP, ESR, FBS, creatinine, d-dimer, hypercoagulation activity, as well as protein C and S are controversial markers. Finally, our study proposed diagnostic panels for laboratory differential diagnosis to be considered at first and in more advanced stages.

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

Background 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. Method 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). Results 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]. Conclusion 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.

T786C eNOS polymorphism as risk factor for recurrent myocardial infarction in young and middleaged patients

Objective. To determine the possible role of the endothelial nitric oxide synthase (eNOS) polymorphism T786C (rs 2070744) in developing of recurrent myocardial infarction (MI) in young and middle-aged patients. Materials and methods. 114 patients with acute MI treated with percutaneous coronary intervention and thrombolysis that were admitted to Clinical cardiologic dispensary (Perm city, Russia) were enrolled into a study. Among them there were 28 patients with recurrent MI. The eNOS T786C polymorphism were determined by real-time PCR. Results. In T786C polymorphism of eNOS, compared with the T/T genotype, it was determined that those with T/C has 2,27 fold (95 % CI: 1.01–5.49), and those with the CC genotype has 2.22 times (95 % CI: 1.30–8.53) (p = 0.034) greater risk of developing recurrent MI. Patients with severe coronary arteries atherosclerosis more frequently had eNOS T786C polymorphism of T/C genotype (OR = 4,67; 95 % CI: 1,38–15,37; p = 0,031). Conclusion. The eNOS T786C variants could be evaluated as recurrent MI risk factor in young and middle-aged patients.

GENES and In-Stent Restenosis: Review

The initiation of coronary stents is a vast landmark in the practice of interventional cardiology. The vascular injury sustained during the percutaneous coronary intervention (PCI) leads to a complicated inflammatory and repairing process. Therefore, stent restenosis arises. Diabetes mellitus is the highest-risk clinical predictor of ISR. Genetics has an important role in the development of ISR. There is a suggested association between the appearance of stent restenosis and certain genetic polymorphisms. Examples of these single nucleotide polymorphisms are endothelial nitric oxide synthase gene (eNOS), the angiotensin converting enzyme gene (ACE), the angiotensin II type 1 receptor gene (AT1R), TGF-β, and VEGF. CYP2C19 variants can help change the medical strategy to a more individualized therapeutic regimen either by altering the therapeutic dose depending on the genotype or using an alternative drug that does not worsen the patient’s case. However, eNOS polymorphism produces gene expression alteration leading to ISR following stent placement. In addition, the deletion-allele of the ACE genotype increases the risk of ISR; however, the I allele decreases the risk. Moreover, the D/I polymorphism is not an independent factor of ISR in patients administering ACE inhibitors or angiotensin receptor antagonists. Furthermore, studies on large sample sizes are required to decrease the harmful adverse effects of stent restenosis by detecting these allele gene polymorphisms.