C242T Polymorphism Research Articles

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.

Specific features of arterial stiffness and endothelial vasomotor dysfunction in patients with joint hypermobility syndrome

Introduction. Joint hypermobility syndrome (JHS) is characterized by a multisystem lesion of organs, including the cardiovascular system, which determines the presence of cardiovascular risks in this pathology. Aim. Studying of arterial stiffness and endothelial dysfunction parameters in patients with JHS. Material and methods. Study population included 105 adults with JHS (90 women and 15 men) and 57 healthy controls (49 women and 8 men) aged 20 to 28 years (mean age 22 [21; 23] years). All persons underwent a general clinical examination; examination of endothelial vasomotor function (EVF) and pulse wave velocity at the carotid-radial segment (PWVcr) by rheography (IMPECARD-M, Belarus); investigation of arterial stiffness parameters: cardio-ankle vascular index (CAVI), cardio-ankle pulse wave velocity (PWVha), ankle-brachial index (ABI), augmentation index (AI) by sphygmography (VaSeraVS-1500N Fukuda Denshi, Japan); determination of T786C polymorphism of the eNOS gene by polymerase chain reaction (Litech, Russia), determination of endothelin-1 and transforming growth factor beta-1 (TGF-β1) levels by enzyme immunoassay (Fine Test, Wuhan Fine Biotech Co., China). Results. According to the main clinical and laboratory indicators, the groups were matched. In patients with JHS, the values of PWV at the carotid-radial and cardio-ankle segments were higher, in other parameters (EVF, CAVI, ABI, AI) the groups were matched. In the group with JHS, pathological values of EVF, PWVcr, CAVI, AI were more often determined. Among patients with JHS, an excess of vascular age over the passport age is detected 8.6 times more often (95% CI from 1.103 to 67.321). These changes are not associated with mutations of the eNOS T786C gene and changes in endothelin-1 and TGF-β1 concentrations. Conclusion. These data indicate the importance of further study of the mechanisms of early vascular changes in the arteries in JHS, in order to develop optimal methods of therapy and improve the cardiovascular prognosis of patients with this pathology

The investigation of the association of alleles and genotypes of the polymorphic marker T786C of the eNOS gene at various stages of primary open-angle glaucoma

Purpose: to study the association of the polymorphic marker T786C of the eNOS gene with various stages of primary open-angle glaucoma (POAG).Materials and methods. Peripheral blood of 90 patients aged 56 to 89 yrs (ave. 71 yrs) with POAG stages I, II, III was tested. DNA was isolated using a set of ribosorbents (Synthol company); subsequently, a real-time PCR reaction was performed on a DT-96 amplifier using the set to determine the polymorphic marker T786C in the eNOS gene.Results. For all groups of patients, the frequency of occurrence of alleles and genotypes was calculated, and the relationship between the emergence of POAG and the presence of an unfavorable polymorphic marker was determined. The main changes were revealed at POAG stages II and III, whilst at stage I no effect of polymorphism T786C of the eNOS gene was observed.Conclusion. For the first time, a comparative assessment was made of the distribution of alleles and genotypes by the polymorphic marker T786C in the eNOS gene of patients with various POAG stages.

The Role of the Vegfa C936t Polymorphism in the Development of Chronic Venous Insufficiency of the Legs And Its Analysis

In 98 patients, an analysis of the genetic risk factor for the development of chronic venous insufficiency was carried out by studying the frequency of distribution of alleles and genotypes of the C936T polymorphism in the VEGFA gene. In both groups, the actual distribution of C807T polymorphism genotypes corresponded to those expected under the Hardy-Weinberg equilibrium (p
 <0.05). A significant relationship was established between the risk of developing chronic venous insufficiency and the distribution of predisposing/protective variants of the C807T polymorphism genotypes in the VEGFA gene. These data allow us to suggest testing this locus to predict the risk of occurrence and progression of chronic venous insufficiency>

Effectof the CYBA C242T Polymorphism on Preeclampsia Pathogenesis in the Chinese Population.

Although the mechanisms responsible for the pathogenesis of preeclampsia (PE) have not been entirely clarified, oxidative stress is thought to be its leading cause. As a major component responsible for reactive oxygen species (ROS) production during oxidative stress, p22phox, encoded by CYBA, is an essential subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The aim of this study was to investigate whether CYBA expression and its polymorphism are associated with PE. Expression of CYBA was analysed in placentas from PE and control groups, as well as in HTR-8/SVneo cells stimulated with CoCl2 and TNF-α. Then, the CYBA C242T polymorphism in 1184 patients with PE and 1421 healthy controls was genotyped using the TaqMan probe, and the different distributions identified were confirmed by a case‒control association study. Expression of CYBA mRNA and protein in the placenta of pregnant women with PE was significantly increased compared to controls. Expression of CYBA mRNA was also increased in HTR-8/SVneo cells collected after 24h of separate stimulation with cobalt chloride and TNF-α. There was no significant difference in the distribution of the C242T locus genotype and CYBA allele frequency between the case group and control group (P > 0.05). CYBA may play a role in the pathogenesis of oxidative stress in PE, in which it may function by cooperating with the TNF-α-related inflammatory pathway. Although no discrepant distribution of the CYBA C242T polymorphism in the Chinese population was detected, it is necessary to examine multiple CYBA SNPs in diverse populations and perform functional experiments to gain further insights into its pathogenesis.

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.

Structural and functional condition of the heart in patients with arterial hypertension depending on A1166C-gene polymorphism of angiotensin II type 1 and T786C-promoter of endothelial NO-synthase gene

It's known that pathological changes in structural and functional condition of the heart, which are caused by arterial hypertension, trigger development of chronic heart failure and disablement of population. Nowadays, it proven that candidate genes, expression products of which participate in regulating vascular tone, have considerable influence upon development of arterial hypertension, however their role in pathogenesis of arterial hypertension has not been fully clarified, and results of the respective researches significantly vary among different populations. To determine the structural and functional state of the heart in patients with hypertension depending on the polymorphism of the A1116C gene of the angiotensin II receptor type I and the T786C promoter of the endothelial NO-synthase gene we examined 86 patients, aged from 45 to 76 years. 30 people without signs of hypertension were in the control group. The structural and functional state of the heart was assessed by cardiac ultrasound according to standard methods. Studies of the A1166C allelic polymorphism of the angiotensin II receptor gene type 1 and the T786C promoter of the eNOS gene were performed by polymerase chain reaction with electrophoretic detection of results. Analysis of cardiac ultrasound showed, that in the patients – carriers of C-allele of both studied genes (AС+СС and TC+CC) left ventricular ejection fraction tended to decrease. We found a bigger thickness of the posterior wall of the left ventricle in patients with CC genotype compared to carriers of AA genotype A1166C – (1.3±0.07) cm vs. (1.1±0.05) cm (p<0.005). The mass of the left ventricular myocardium index in the group of patients with the genotype AC and CC was (157.5±7.3) g/m2 and (161.5±7.1)) g/m2, respectively, being by 16.7% and 19.6% more than in carriers of AA genotype of the AGTR1 gene. In the groups of patients-carriers of C-allele (TC+CC) of the eNOS gene the mass of the left ventricular myocardium index values were (155.2±11.4)) g/m2 and (158.4±7.9)) g/m2, respectively, which is by 5.4% and 7.5% more than in carriers of TT genotype. The mean size of the left atrium was significantly higher in patients who had AC and CC genotype of the AGTR1 gene, as well as TC and CC genotype of the eNOS gene compared with the control group. Carriers of C-allele (AC+CC genotype) of AGTR1 gene polymorphism had clearly bigger sizes of the left atrium, as compared to homozygotes by A-allele. The severity of diastolic dysfunction was higher in carriers of the CC genotype of the AGTR1 gene and the eNOS gene than in heterozygotes of the studied genes by 4.3% and 3.3%, respectively. The research shows that inheritance of CC genotype for A1166C polymorphism of the the angiotensin II type 1 receptor gene and of CC T786C polymorphism in the promoter of eNOS gene is associated with more noticeable changes in structural and functional heart condition among patients with arterial hypertension.

#3145 ASSOCIATION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE POLYMORPHISM WITH ENDOTHELIAL DYSFUNCTION IN DIABETIC NEPHROPATHY AMONG AZERBAIJANIS

Abstract Background and Aims Vascular endothelial dysfunction resulting from impaired nitric oxide synthase (NOS) activity in the endothelial cells of blood vessels has been suggested as playing an important role in the pathogenesis of Diabetic nephropathy (DN). It regulates endothelial function and maintains endothelial-dependent vasodilation in multiple organs, including the kidney. The study was carried out to investigate the association of T-786C single nucleotide polymorphisms with the flow mediated dilation (FMD) in DN among type 2 diabetic subjects. Method 90 patients (45 male and 45 female) with diabetic nephropathy were recruited from Nephrology and Endocrinology departments of the Azerbaijan Medical University hospital. As a control group the results were compared with the findings in 100 healthy Azerbaijani individuals (50 males and 50 females). The study was approved by ethics committee and informed consent was obtained from all patients in written form. Brachial endothelial function was determined by brachial artery vasodilator response or brachial FMD in the dominant arm according to previously validated techniques. T786C polymorphism was detected using polymerase chain reaction-restriction fragment length polymorphism analysis. Results The results showed significant differences between DN group and control group regarding the genotype and allele distributions of the T786C single nucleotide polymorphisms. The CC genotype was significantly more frequent in diabetics nephropathy patients than in control group (42% vs. 8%, p = 0.01). FMD in allele homozygote T786C(TT), T786C(CC) and heterozygote T786C(CT) were respectively 13.5 ±0.16%, 12.3±0.19%,13.9 ±0,28%. In the study groups, Azerbaijani patients showed dominance of the C allele and a mutant homozygous genotype CC of the T786C gene of eNOS. Subjects with the 786C(CC) (n = 48) showed significantly reduced FMD with those with T786C (TT) (n = 7) (p = 0.021) and T786C (CT) (n = 35) (p = 0.023), whereas there was no significant difference in endothelial-independent vasodilation between these groups. Although subjects with homozygote T786C(TT), did not show significantly reduced levels of FMD. Who were carriers of the T786C allele demonstrated markedly reduced levels of FMD compared with noncarriers (p = 0.019). Conclusion The data suggest that in diabetic nephropathy, the eNOS T786C allele may be involved in endothelial dysfunction. Azerbaijani patients showed dominance of the C allele and a mutant homozygous genotype CC of the T786C gene of eNOS.

Effect of treatment on genetic predictors and quality of life in rheumatoid arthritis patients with type 2 diabetes, hypertension, and obesity

Background. Connective tissue disease, in particular rheumatoid arthritis (RA), is characterized by a progressive joint damage and polymorphism of extra-articular lesions that affect the patient’s quality of life. Although the widespread implementation of basic therapy through the use of disease-modifying antirheumatic drugs has a positive effect on social consequences, the experience gained shows the impossibility of achieving a stable remission of the disease or reducing the activity of autoimmune inflammation against the background of using these medicines in all patients for a number of reasons. One of these reasons is the presence of comorbid pathology, which requires a personalized approach to each person. The objective was to study the quality of life of patients with RA in combination with type 2 diabetes mellitus (T2DM), hypertension and obesity depending on the T-786C polymorphism of the endothelial nitric oxide synthase gene promoter. Materials and methods. A laboratory and instrumental examination involved 110 patients who were treated at the clinical base of the Department of Internal Medicine of Bukovinian State Medical University, Chernivtsi Regional Endocrinology Center, Chernivtsi Regional Clinical Hospital, and Reference Center for Molecular Genetic Research of the Ministry of Health of Ukraine. Results. When assessing the quality of life in the studied groups, a decrease in indicators on all scales was detected. Thus, in RA combined with hypertension and obesity, PF was 1.73 times lower, RP— 1.97 times, BP— 1.44 times, SF— 1.46 times, MH— 1.26 times , RE— 1.66 times, GH— 1.35 times (p<0.05) lower than in patients with isolated RA. Taking into account the T-786C polymorphism of the eNOS gene, it can be asserted that all indicators of quality of life were reduced in the carriers of the СС genotype, in contrast to the carriers of the T-allele: PF— by 2.06 (pTT<0.05) and 2.46 times (pTС<0.05); RP— by 2.0 (pTT<0.05) and 2.87 times (pTС<0.05); BP— by 1.86 (pTT<0.05) and 2.52 times (pTС<0.05); SF— by 1.55 and 2.07 times (рTС<0.05); MH— by 1.42 (pTT<0.05) and 1.53 times (pTС<0.05); RE— by 1.30 (pTT<0.05) and 1.54 times (pTС<0.05); VT— by 3.34 (pTT<0.05) and 3.72 times (pTС<0.05); GH— by 2.32 (pTT<0.05) and 2.38 times (pTС<0.05), respectively. Conclusions. When comparing the quality of life in the studied groups, it can be stated that the lowest indicators on all scales were in patients with RA combined with hypertension, obesity and T2DM and in carriers of the СС genotype of the analyzed gene, which reflected the worst physical condition and psychosocial status.

Association of osteoporosis risk and polymorphisms of osteoprotegerin gene T950C in postmenopausal Chinese women: A PRISMA-compliant meta-analysis.

This study aimed to assess the association between the T950C polymorphism and osteoporosis in postmenopausal Chinese women to further reduce the influence of different genetic backgrounds by meta-analysis and subgroup analysis. Through November 2022, a systematic online investigation was performed with the aid of the Cochrane Library, EMBASE, PubMed, Web of Science and the Chinese National Knowledge Infrastructure to find case-control studies looking into the correlation between the osteoprotegerin gene (OPG) T950C polymorphism and postmenopausal osteoporosis susceptibility. This study included 6 studies with a total of 1669 postmenopausal osteoporosis cases and 2992 controls. In the recessive model, postmenopausal women with the CC genotype (mutant homozygote at the T950C locus) had a lower risk of osteoporosis, indicating that the CC genotype of OPG T950C might show a preventive effect on osteoporosis after menopause. In a stratified analysis by geographic area, the population from South China had a significantly higher risk under the dominant model [CC + TC (heterozygote at the T950C locus) vs TT (wild-type homozygotes at the T950C locus): odds ratio = 1.34, 95% confidence interval = 1.17-1.54, P < .01], while the population from South China had a significantly lower risk under the recessive model (CC vs TC + TT: odds ratio = 0.79, 95% confidence interval = 0.69-0.95, P = .02). Together, the OPG T950C polymorphism may be associated with osteoporosis risk in postmenopausal Chinese women, according to this meta-analysis. Because of the study's limitations, more large-scale research is needed to corroborate these findings.

The association between C509T, T869C, G915C gene polymorphisms of transforming growth factor-β1 and systemic lupus erythematosus risk: A meta-analysis.

The relationship between transforming growth factor-β1 (TGF- β1) gene polymorphisms and systemic lupus erythematosus (SLE) has been reported in many studies, but there were still controversies with regard to their conclusions. Relevant documents were retrieved from 5 electronic databases such as PubMed, Embase, Cochrane Library, Wanfang, and China national knowledge infrastructure. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to assess the relationship between TGF-β1 genetic variation and SLE. The present meta-analysis included 12 case-control studies with 1308 SLE patients and 1714 healthy controls. The results of the combined analyses showed that TGF-β1 C509T polymorphism showed no association with SLE risk (TC vs CC: OR = 1.16, 95% CI = 0.91-1.48, PHeterogeneity (PH) = 0.579; TT vs CC: OR = 1.15, 95% CI = 0.63-2.09, PH = 0.003; T vs C: OR = 1.08, 95% CI = 0.8-1.45, PH = 0.003; TC/TT vs CC: OR = 1.17, 95% CI = 0.93-1.46, PH = 0.133; and TT vs TC/CC: OR = 1.06, 95% CI = 0.64-1.76, PH = 0.004). TGF-β1 G915C and T869C polymorphisms were not linked with SLE risk. Moreover, subgroup analysis stratified by ethnicity and Hardy-Weinberg equilibrium revealed no significant correlation of TGF-β1 T869C, C509T, G915C polymorphisms with SLE risk. TGF-β1 T869C, C509T, G915C polymorphisms might not be associated with the development of SLE.

Metalloproteinases as biomarkers of chronic obstructive pulmonary disease progression

According to the World Health Organization, chronic obstructive pulmonary disease is the third leading cause of death in 2020, accounting for approximately 6% of all deaths.Aim. We studied how matrix metalloproteinases affect the likelihood and severity of chronic obstructive pulmonary disease.Methods. The study included 60 patients aged 40 to 85 years with chronic obstructive pulmonary disease (7 women and 53 men). The average age of the patients was 63.2 ± 8.3 years. The smoker index ranged from 10 to 118 pack/years. We divided all examined patients into two groups by the severity of the disease, by age, by the duration of the disease, and by the clinical forms.Results. Among the 60 examined patients, we did not identify a single patient with polymorphic variant C536T of TIMP-1 gene. All patients were homozygous and had the CC genotype. We found that only C-1562T polymorphism of MMP-9 gene is associated with severe COPD (p = 0.014), out of all studied variants of MMP-1, MMP-9, and MMP-12 genes. We did not find a reliable relationship between polymorphic variant C-1562T of MMP-9 gene and emphysematous changes in the lungs. We did not find a significant effect of polymorphic variants of MMP-1 and MMP-12 genes on the severity of COPD and the nature of structural changes in the lung tissue. As a result, we can assume that future studies should focus more on the relationship between the dominant pathogen and the level of matrix metalloproteinases. Understanding this relationship will allow us to influence the course and prognosis at an earlier stage of the disease. Our data on the leading role of polymorphism of MMP-1, MMP-9, and MMP-12 genes and other candidate genes are also confirmed by other recently published scientific papers.Conclusion. This study established the presence of genetic markers for a poor prognosis of COPD. Smokers and people subject to occupational hazards are most susceptible to these factors.

Polymorphisms of the Matrix Metalloproteinase Genes are Associated with Acute Ischemic Stroke in Chinese Han Population.

Studies have shown that matrix metalloproteinase (MMP-2,3,9) plays an important role in the pathologic process of ischemic stroke (IS). The aim of this study was to investigate the relationship between C1306T, 1612-5A/6A, C-1562T polymorphisms of MMP-2,3,9 genes and IS in Chinese Han population. The polymorphisms of MMP-2(C1306T), -3(1612-5A/6A), -9(C-1562T) gene were detected by PCR-RFLP and SNaPshot sequencing. Then, stratified analysis was used to study the relationship between IS subtypes and MMP-2,3,9 polymorphisms. For the MMP-2 gene C1306T polymorphism, TT genotype and T allele were significantly associated with a reduced risk of IS (P = 0.015, P = 0.003, respectively). T allele was significantly associated with a reduced risk of small artery occlusion (SAO) subtype compared with the control group (P = 0.012, OR = 0.550, 95% CI = 0.065-1.291). For the MMP-3 gene-1612 (5A/6A) polymorphism, 5A/5A genotype was significantly increased in the IS group (P = 0.011, OR = 0.370, 95% CI = 0.168-0.814), especially in the large-artery atherosclerosis (LAA) subtype (P = 0.001, OR = 2.345) as compared to the control group. Our study suggested that the T allele of MMP-2 may be a protective factor of IS, especially in SAO subtype, while the 5A/5A gene of MMP-3 may increase the risk of IS, especially in LAA subtype in Chinese Han population.

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.

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.

Association between OPG polymorphisms and osteoporosis risk: An updated meta-analysis.

Background: Numerous studies have demonstrated an association between osteoprotegerin (OPG) polymorphisms (A163G (rs3102735), T245G (rs3134069), T950C (rs2073617), G1181C (rs2073618)) and osteoporosis risk. However, their conclusions are inconsistent. In addition, some new studies have been updated, and more importantly, previous meta-analyses have not tested for false-positive results. In order to further explore these associations, we recently conducted a meta-analysis. Objectives: To study the relationship between OPG polymorphisms A163G, T245G, T950C, G1181C and the risk of osteoporosis. Methods: PubMed, Medline, International Statistical Institute (ISI), China National Knowledge Infrastructure (CNKI) and China Wanfang Database were used for research searches. Associations were assessed with five genetic models using odds ratios (ORs) with 95% confidence intervals (CIs). In addition, confidence in statistically significant associations was assessed using false-positive report probability (FPRP), Bayesian probability of False discovery (BFDP), and Venice criteria. Results: On the whole, the OPG A163G polymorphism was not significantly associated with risk of osteoporosis. However, in a subgroup analysis, we found that the OPG A163G polymorphism increased the risk of osteoporosis in Caucasians (AG + GG vs AA: OR = 1.35, 95% CI = 1.06-1.73; AA + GG vs AG: OR = 0.64, 95% CI = 0.49-0.82) and the female (G vs A: OR = 1.30, 95% CI = 1.03-1.64; AG + GG vs AA: OR = 1.42, 95% CI = 1.18-1.71). At the same time, the OPG G1181C polymorphism reduces the risk of osteoporosis (C vs G: OR = 0.84, 95% CI = 0.74-0.95; CC vs GG: OR = 0.75, 95% CI = 0.60-0.93; GC + CC vs GG: OR = 0.80, 95% CI = 0.67-0.95; CC vs GG + GC: OR = 0.84, 95% CI = 0.70-1.00). Moreover, a significantly decreased risk of osteoporosis was also discovered in Asian (C vs G: OR = 0.80, 95% CI = 0.66-0.98; CC vs GG: OR = 0.67, 95% CI = 0.47-0.95; GC + CC vs GG: OR = 0.74, 95% CI = 0.58-0.95) and the female (C vs G: OR = 0.85, 95% CI = 0.75-0.97; CC vs GG: OR = 0.77, 95% CI = 0.61-0.96; GC + CC vs GG: OR = 0.79, 95% CI = 0.66-0.95). Finally, we did not find a close association between OPG T245G and T950C polymorphisms and osteoporosis risk. However, when we retained only studies in the control group that was consistent with Hardy-Weinberg equilibrium (HWE) and high-quality scores, we observed that the OPG A163G polymorphism increased the risk of osteoporosis in the overall analysis (G vs A: OR = 1.40, 95% CI = 1.16-1.68; GG vs AA: OR = 1.96, 95% CI = 1.20-3.21; AG + GG vs AA: OR = 1.45, 95% CI = 1.22-1.72). Finally, after the credibility assessment, we concluded that all statistically significant association results in the meta-analysis in this study and those in the previous study were 'positive results with low confidence'. Conclusion: In conclusion, our study concluded that all meaningful results between OPG A163G and G1181C polymorphisms and osteoporosis risk were false-positive results rather than true associations.

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.

ENOS T786C (rs2070744) Gene Polymorphism and Its Underlying Mechanism Associated with Coronary Heart Disease

The study aims to examine plasma nitric oxide concentration and its relationship to T-786C gene polymorphism levels in the development of coronary heart disease in young people. Reduced nitric oxide (NO) bioavailability and endothelial nitric oxide synthase (eNOS) T786C gene polymorphism have been identified as risk factors for the development of coronary heart disease. This cross-sectional study was conducted in SRM Medical College Hospital and Research Centre on 200 angiographically proven CHD subjects attending the Department of Cardiology and medicine and 100 controls from MHC in the age group of ≤ 45 years. Overnight fasting plasma samples were obtained to evaluate lipid profile and nitric oxide by Griess reaction in UV spectrophotometry utilizing the ELISA technique. Polymerase Chain Reaction and Restricted fragment length polymerase amplify the eNOS gene T-786C. As a result, NO levels in plasma were significantly lower in CHD patients than in controls. In addition, C allele carriers of the eNOS T786C polymorphism showed significantly lower mean plasma NO levels than T allele carriers (P &lt; 0.001). Our findings suggest that a lower plasma NO level is related to an increased risk of CHD. Furthermore, the eNOS T786C polymorphism is a significant risk factor for CHD development by lowering NO levels in the plasma. However, the eNOS T786C polymorphism influences the severity of CHD.

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.

Влияние полиморфизмов 894G/T и Т786С гена эндотелиальной синтазы оксида азота на уровень продуктов их экспрессии — eNOS и NOу детей с артериальной гипертензией

The purpose — to study the effect of the polymorphic variants 894G/T and T786C of NOS3 gene of the endothelial nitric oxide synthase gene on the levels of their expression products — eNOS and NO in children with arterial hypertension. Material and methods. We examined 111 children, including 51 patients with arterial hypertension, 30 patients with high-normal blood pressure and 30 healthy children. The polymorphism of the study genes was studied using a real-time polymerase chain reaction. Determination of plasma concentrations of eNOS was performed with enzyme immunoassay. NO metabolites, nitrateandnitrite (NOx) production were determined using the Griess reaction. Results. Among the children of the Grodno region, the homozygous GG genotype and the G-allele of the polymorphic locus 894G/T of the NOS3 gene and the heterozygous TC genotype and the T-allele of the T786C polymorphic variant of the NOS3 gene predominate. The presence of the T allele 894G/T of the NOS3 gene in children with arterial hypertension is associated with a decrease eNOS expression and NOx levels compared with T allele carriers among healthy children. Heterozygous genotype 786TC and allele C of T786C polymorphism of the NOS3 gene in children with arterial hypertension are characterized by a low level of NOx compared with healthy children.