C242T Polymorphism Research Articles

Brain Abscess Risk Associated with Genotypic Polymorphism of the Matrix Metalloproteinase-1, -2, -3, and -9 in North Indian Population

BackgroundBrain abscess develops in response to a parenchymal infection due to pyogenic bacteria. MMPs (matrix metalloproteinases) play vital role in many infectious and central nervous system (CNS) diseases. The present study evaluated the association of specific alleles/ genotypes of MMP-1, -2, -3, and -9 with brain abscess.MethodsA total of 100 brain abscess patients and 100 healthy controls were included in the study. Predisposing factors were identified in 70 brain abscess patients. Out of 100 brain abscess samples, 66 were culture positive. MMP-1-1607 1G/2G, MMP-2- C-1306-T, MMP-3 -1171 5A/6A, and MMP-9 C-1562Tgenotypes were detected by PCR-RFLP. Levels of these MMPs were determined in patients’ sera by ELISA and correlated with different genotypes.ResultsThe genotypic distributions of MMP-1-1607 1G/2G, MMP-2- C-1306-T, MMP-3 -1171 5A/6A, and MMP-9 C-1562T were significantly different between patients and controls. Homozygous genotype of MMP-1, -3, and -9 (P < 0.001, P = 0.04, and P = 0.03, respectively) and heterozygous genotype of MMP-2 (P < 0.001) showed significant association with brain abscess. Individuals with mutant genotypes had elevated levels of these MMPs. Furthermore, heterozygous (5A/6A and C/T, respectively) genotypes of MMP-3 and -9 also showed significant association with brain abscess patients having predisposing factors. When comparison was made between culture positive and culture negative results, of MMP-1 2G/2G and MMP-9 T/T, C/T genotype showed significant association with culture positive patientsConclusionPolymorphism of MMP-1-1607 1G/2G, MMP-2- C-1306-T, MMP-3 -1171 5A/6A, and MMP-9 C-1562T polymorphisms lead to increased production of these molecules, which appear to be a risk for the development of brain abscess in North Indian population.Disclosures All authors: No reported disclosures.

C-1562T polymorphism of matrix metalloproteinase-9 (MMP-9) gene associated with elevated level of plasma MMP-9 concentration in patient with acute myocardial infarction (AMI) in Denpasar-Bali

C-1562T polymorphism of matrix metalloproteinase-9 (MMP-9) gene associated with elevated level of plasma MMP-9 concentration in patient with acute myocardial infarction (AMI) in Denpasar-Bali

Endothelial nitric oxide synthase gene (T786C and G894T) polymorphisms in Egyptian patients with type 2 diabetes.

BackgroundGenetic factors play important role in the development of type 2 diabetes and diabetic nephropathy. Endothelial nitric oxide synthase (eNOS) gene is responsible for the bioavailability of nitric oxide and endothelial function.AimTo assess the association of the endothelial nitric oxide synthase (eNOS) (T786C and G894T) single nucleotide polymorphisms with Egyptian type 2 diabetes mellitus and diabetic nephropathy.Patients and methodsA total of 200 type 2 diabetic patients and 100 apparently healthy volunteers as controls were included in the study. They were subjected to clinical examination and laboratory tests: fasting blood glucose, HBA1C, lipid profile, serum creatinine, blood urea and albumin creatinine ratio (ACR). Assessment of the T786C and G894T polymorphisms in the eNOS gene was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThere was no significant difference in distribution of eNOS T-786C polymorphism between patients and controls; TT genotype of eNOS G894T was more frequent in diabetic patients with and without albuminuria compared to controls. Patients were divided into 3 groups according to ACR. Normoalbuminuria: 37 patients with ACR ≤ 30 mg/g, microalbuminuria: 96 patients with ACR > 30 mg/g and ≤ 300 mg/g, and macroalbuminuria: 67 patients with ACR > 300 mg/g. There was no significant difference in genotype distribution of eNOS T-786C between the 3 groups of diabetic patients. The prevalence of TT genotype of eNOS G894T was higher in microalbuminuria patients compared to other groups.ConclusioneNOS G894T variant may increase risk of type 2 diabetes with lack of association between eNOS T786C, eNOS G894T and DN in Egyptians.

Association of T-786C polymorphism of endothelial nitric oxide synthase 3 gene with the functional state of the myocardium in patients with ischemic heart disease combined with type 2 diabetes mellitus

The association of polymorphism T-786C of the endothelial NO-synthase gene NOS3 with the functional state of the left ventricle (LV) was studied among residents of the West Siberian region with ischemic heart disease (IHD), including that combined with diabetes mellitus type 2 (DMT2). Carriers of genotype–786TT had the greatest ejection fraction of the left ventricle in the group of patients without DMT2 (p = 0.012). This dependence was not revealed in the group of patients with IHD combined with DMT2. In the group with genotype–786TC, the frequency of left ventricular hypertrophy was higher among patients with DMT2 than patients without it (p = 0.025). There was no association between NOS3T–786C polymorphism and the severity of functional class of heart failure in both the groups.

Is the C242T Polymorphism of the CYBA Gene Linked with Oxidative Stress-Associated Complications of Prematurity?

The C242T polymorphism of CYBA (cytochrome B-245 alpha chain), the gene encoding the p22phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, has been linked to several conditions in which oxidative stress plays a pathogenic role. We investigated in a cohort of 451 preterm infants [gestational age (GA) ≤30 weeks] the association of the polymorphism with the risk of developing neonatal respiratory distress syndrome (RDS), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, patent ductus arteriosus, or intraventricular hemorrhage. We observed a significant association of the TT/CT genotype with RDS [odds ratio (OR) 2.34, 95% confidence interval (95% CI) 1.28-3.90], ROP (OR 1.72, 95% CI 1.05-2.80), and BPD (OR 1.60, 95% CI 1.05-2.43). When this dominant model was adjusted to account for GA, birth weight, and sex, it remained significant for the three outcomes. This study is the first to address the association of a polymorphism related to the NADPH family with oxidative stress-related complications of prematurity. Since p22phox is essential for reactive oxygen species production by NADPH oxidase, we hypothesize that genetic variations in the protein may lead to differences in susceptibility to oxidative stress-induced damage in preterm infants. Antioxid. Redox Signal. 27, 1432-1438.

Association of R279Q and C1562T polymorphisms of matrix metalloproteinase 9 gene and increased risk for myocardial infarction in patients with premature coronary artery disease.

A number of matrix metalloproteinase (MMP) gene polymorphisms has been identified which may be probably related to premature myocardial infarction (MI). We assessed the relationship between the two polymorphisms of the MMP9 gene including R279Q and C1562T and occurrence of premature MI. The study has two phases including a case-control study as the first phase and cohort study as the second phase. Initially, 1000 patients with premature coronary artery disease were classified into MI and non-MI groups. Genotyping of the polymorphism was conducted by PCRRFLP and high-resolution melting techniques. Given the two conditions of patients residing in Tehran and faced with their first episode of MI, 640 of 1000 study samples previously followed up with a median follow-up time of 45.74months were assessed in a retrospective cohort phase regarding long-term major adverse cardiac events (MACE). The prevalence of wild, heterozygous, and mutant genotypes of R279Q polymorphism in MI group was 14.5%, 57.3%, and 28.2% and in non-MI group was 36.9%, 38.4%, and 24.7%, respectively, with a considerable difference (P<.001). There was a significant difference in the prevalence of wild, heterozygous, and mutant genotypes of C1562T polymorphisms in MI group (12.4%, 41.2%, and 46.4%, respectively) and in non-MI group (46.8%, 38.6%, and 14.7%, respectively; P<.001). No difference was found in total MACE-free survival rate between genotypes of R279Q and C1562T polymorphisms. C1562T and R279Q polymorphisms are associated with the susceptibility to premature MI, but cannot predict long-term cardiac events in these patients.

NADPH oxidase p22phox C242T polymorphism is associated with macroalbuminuria in diabetic patients: A meta-analysis

AimsPrevious studies suggested an association between C242T polymorphism in NADPH Oxidase p22phox and diabetic nephropathy (DN) risk, but the results were inconsistent. To obtain a more precise estimation, we carried out a meta-analysis to analyze the effect of C242T polymorphism in NADPH Oxidase p22phox on DN risk. MethodsWe searched PubMed, ISI Web of Science, and China National Knowledge Infrastructure for all eligible case–control studies through May 2016. The odds ratios (ORs), together with the 95% confidence intervals (CIs), were calculated to evaluate the strength of association between C242T SNP in NADPH Oxidase p22phox on DN risk. ResultsOverall, ten eligible studies involving a total of 1894 cases and 1746 controls were included in our meta-analysis. The results showed that there was no statistical evidence of association between NADPH oxidase p22phox C242T polymorphism and DN in all genetic models (T vs. C: OR 1.16, 95% CI 0.85–1.59, p=0.34; TT vs. CC: OR 1.49, 95% CI 0.80–2.76, p=0.21; TT/CT vs. CC: OR 1.18, 95% CI 0.81–1.72, p=0.40; TT vs. CT/CC: OR 1.31, 95% CI 0.82–2.11, p=0.26). However, significant association was found in diabetic patients with macroalbuminuria. ConclusionThis meta-analysis indicates that NADPH oxidase p22phox C242T polymorphism is associated with macroalbuminuria in diabetic patients. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous patients and well-matched controls are required.

Adverse prognostic impact of TGFB1 T869C polymorphism in non-small-cell lung cancer.

Previously, several polymorphisms in TGFB1 have been identified in non-small-cell lung cancer (NSCLC), and the variants, C-509T, T869C, and G915C, have been demonstrated to associate with higher circulating levels of TGF-β1. However, little is known about the prognostic value of TGF-β1 polymorphisms in cancers. In this study, by genotyping the TGF-β1 T869C polymorphism in a total of 261 patients with NSCLC using DNA from blood lymphocytes, we first found that NSCLC patients, especially those with allele C carriers, had significantly higher serum TGF-β1 levels than healthy individuals. By using chi-square (χ2) test and Fisher’s exact test, we noticed that TC/CC genotypes were positively correlated with smoking, clinical TNM stage, lymph node, and distant metastasis in NSCLC patients. Kaplan–Meier analysis showed that patients with TT genotype had a better overall survival than the allele C carriers (TC + CC). Finally, multivariate analysis confirmed histology, lymph node, and distant metastasis but not T869C polymorphism as independent prognostic factors for NSCLC. Taken together, our data, as a proof of principle, suggest that T869C polymorphism in TGFB1 may act as a genetic modifier in NSCLC progression and a promising prognostic marker of survival in NSCLC patients.

Association of MMP-9 gene polymorphisms with nephrolithiasis patients.

Nephrolithiasis is one of the causes which lead to chronic kidney disease (CKD). Matrix metalloproteinases (MMPs) are endopeptidases degrading extracellular matrix which correlate with the pathogenesis of atherosclerosis. The current study was designed to analyze the association of (R279Q, C1562T) polymorphism of MMP-9 with nephrolithiasis patients. Genotyping of MMP-9/R279Q and of MMP-9/C1562T polymorphism were carried out by PCR-based restriction digestion method. Serum level of MMP-9, oxidative stress marker, MDA, and uric acid were measured in patients and control. Allele frequencies of the MMP-9/C1562T polymorphism for C and T allele were 71.25% and 28.75% in patients, 87.08% and 12.92% in control respectively. The homozygote TT was more frequent in the nephrolithiasis patients group, while T allele frequency was significantly higher in the nephrolithiasis patients group than in the control group. The patients with CT and TT genotype showed a significant increase in serum MMP-9, Total Oxidant Status (TOS), Oxidative Stress Index (OSI), Malondialdehyde (MDA), and uric acid when compared to CC genotype in patients with nephrolithiasis. The R279Q polymorphism site with regard to the relationship with nephrolithiasis was not significant. The result indicates that patients with TT genotype had an increased risk of stones. Also, the results demonstrate that TT allele of the C1562T polymorphism in the MMP-9gene is related with an increase of oxidative stress in nephrolithiasis patients and may possibly impose a risk for cardiovascular diseases in patients with TT genotype of MMP-9.

The Endothelial Nitric Oxide Synthase Gene T-786C Polymorphism Increases Myocardial Infarction Risk: A Meta-Analysis.

BackgroundPolymorphisms of the endothelial nitric oxide synthase (eNOS) gene are reportedly associated with myocardial infarction (MI) risk. However, definitive evidence of this association is lacking. In this study, we investigated the potential association of eNOS gene polymorphisms with MI risk by conducting a meta-analysis of studies evaluating this association.Material/MethodsPubMed, Web of Knowledge, ScienceDirect, China National Knowledge Infrastructure (CNKI), WanFang, and Database of Chinese Scientific and Technical Periodicals (VIP) were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated to evaluate the association of eNOS gene T-786C and 4b4a polymorphisms with MI risk.ResultsFifteen studies with 8,067 controls and 4,923 MI cases were included in the final meta-analysis. In the overall analysis, T-786C (rs2070744) polymorphism was associated with MI risk (p<0.05, OR=1.69, 95% CI: 1.53–1.86 for T vs. C; p<0.05, OR=2.76, 95% CI: 2.03–3.75 for TT vs. CC; p<0.05, OR=1.74, 95% CI 1.56–1.95 for TT vs. (CT + CC); p<0.05, OR=2.43, 95% CI: 1.79–3.30 for (CT + TT) vs. CC). In addition, a significant association between 4b4a VNTR polymorphism and MI risk was observed. On sub-group analyses by ethnicity, a significant increase in MI risk was observed separately for Asian and Caucasian populations for T-786C polymorphism, but not for the 4b4a polymorphism.ConclusionsIn this meta-analysis, T-786C polymorphism of the eNOS gene was associated with the risk of MI, especially in the Asian populations.

Association of the Endothelial Nitric Oxide Synthase Gene T786C Polymorphism with In-Stent Restenosis in Chinese Han Patients with Coronary Artery Disease Treated with Drug-Eluting Stent.

Background and aimMany studies have reported that genetic variants correlate with higher risk for coronary artery disease (CAD) or in-stent restenosis (ISR) after bare metal stent (BMS) implantation. However, there is limited data assessing the impact of these variants on ISR in patients treated with drug-eluting stent (DES). The purpose of this study was to investigate the effects of genetic risk factors on ISR in Chinese Han patients treated with DES.MethodsA total of 425 patients with a diagnosis of CAD who underwent successful revascularization in native coronary arteries with DES were included in this retrospective study. Genotyping was performed on six single nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase gene (eNOS), the angiotensin converting enzyme gene (ACE), the angiotensin II type 1 receptor gene (AT1R), the transforming growth factor beta gene (TGF-β), and the vascular endothelial growth factor gene (VEGF). Quantitative coronary angiography (QCA) was performed during the follow-up period to detect ISR. Logistic regression models were used to test for association.ResultsFifty-four patients (12.7%) developed ISR during the follow-up period. Of the six analyzed SNPs, the frequency of the C allele of T786C polymorphism in eNOS was significantly higher in the ISR group (22.2%) compared to the non-ISR group (12.7%) (p<0.01). In the ISR group, the frequency of the TT, TC, and CC genotypes was 61.1%, 33.3%, and 5.6%, respectively, and in the non-ISR group, the frequencies were 76.8%, 21.0%, and 2.2%, respectively. The multivariable analysis adjusted for potential confounders and revealed that the T786C polymorphism increased the risk of ISR in both additive and dominant models with odds ratios of 1.870 (95% confidence interval [CI]: 1.079–3.240, p = 0.03) and 2.045 (95% CI: 1.056–3.958, p = 0.03), respectively.ConclusionThe eNOS T786C polymorphism was associated with ISR in Chinese Han patients treated with DES. Genotyping may be helpful to identify patients with higher risks of ISR after DES implantation.

Atherosclerosis: analysis of the eNOS (T786C) gene polymorphism.

The coronary arteriosclerotic disease is the most common cardiovascular disease. Atherosclerosis affects large- and medium-sized arteries leading to severe thrombosis or artery stenosis that could evolve to myocardial infarction, ischemic stroke, ischemic injury of kidneys and intestines, and several other life-threatening clinical manifestations. Nitric oxide has been shown to be a promising therapeutic agent against cardiovascular diseases. The eNOS gene assumes several important functions, including regulation of vascular tone and regional blood flow, the suppression of vascular smooth muscle cell proliferation, and modulation of leukocyte-endothelium interactions. The T786C polymorphism is an important point mutation, where thymine is changed to cytosine. T786C significantly reduces the activity of the eNOS promoter gene. Two hundred and ninety-seven peripheral blood samples were collected from patients with the previous diagnosis of atherosclerotic disease based on clinical examination and confirmed by imaging methods. Results were compared using the chi-square test and the G-test. In the present study, the TC genotype was more frequent in both case and control groups with no statistically significant difference. Comparing the relation TC/TT and CC genotypes in the case and control groups, there was no statistically significant difference. No significant difference was found when genotypes were analyzed regarding gender and smoking. Our results suggest a strong tendency of the T allele, in single or double dose, to be associated with atherosclerosis that was not confirmed by the scientific data.

ПОЛИМОРФИЗМ ГЕНА ЭНДОТЕЛИАЛЬНОЙ СИНТАЗЫ МОНООКСИДА АЗОТА. ЧАСТЬ 2. ПОЛИМОРФНЫЕ ВАРИАНТЫ T786C, 4A/B

Background. The T786C polymorphism as well as polymorphism of the variable number of tandem repeats in the&nbsp;4th intron (4a/b) of the endothelial nitric oxide synthase gene are important for the processes of NO formation in the&nbsp;organism.The aim. To analyze the literature and our own data on the distribution of allele frequencies and genotypes, as well&nbsp;as physiological and pathogenetic features of the T786C and 4a/b polymorphisms.Material and methods. To analyze the literature 41 scientific publications (2 native and 39 foreign ones) for the&nbsp;period from 2009 to 2016 have been selected.Results. The polymorphic variants T786C and 4a/b of the endothelial nitric oxide synthase gene are associated&nbsp;with the development of a number of pathologies and manifestation of physiological functions in the body.Conclusions. Certain distribution of allele frequencies and genotypes of the T786C and 4a/b polymorphisms&nbsp;accounts for a number of diseases. Studying the T786C and 4a/b polymorphisms is important for understanding themechanisms of oxygen homeostasis in the body.

Assessment of the role of plasma nitric oxide levels, T-786C genetic polymorphism, and gene expression levels of endothelial nitric oxide synthase in the development of coronary artery disease.

Background:Reduced bioavailability of nitric oxide (NO) and the T-786C polymorphism of endothelial nitric oxide synthase (eNOS) gene have been reported as risk factors for the development of coronary artery disease (CAD) with conflicting results. We investigated the association of plasma NO levels, T-786C genetic polymorphism, and gene expression levels of eNOS with CAD risk in an Iranian subpopulation.Materials and Methods:Studied population included 100 patients with angiographically verified CAD and 100 ethnically matched controls. Analysis of T-786C genetic polymorphism and gene expression levels of eNOS was conducted by polymerase chain reaction (PCR) restriction fragment length polymorphism and real-time reverse transcription-PCR methods, respectively. Plasma levels of NO were measured using Griess method.Results:The CC genotype distribution (15% vs. 6%, P = 0.011) and minor C allele frequency (36.5% vs. 21.5%, P = 0.001) of eNOS T-786C polymorphism differed significantly between CAD patients and control. Furthermore, eNOS T-786C polymorphism was more common among smoker than nonsmoker CAD patients (27.7% vs. 7.8%, P = 0.044). The association of the eNOS T-786C polymorphism with the severity of CAD (number of diseased vessel) was significant (P < 0.05). The gene expression levels of eNOS were significantly lower in the heterozygote (0.49 ± 0.1, P = 0.023) and mutant homozygote (0.36 ± 0.09, P = 0.011) genotypes than that of wild-type genotype (P < 0.05). In addition, NO levels were significantly lower in CAD patients compared with control subjects (42.62 ± 12.26 vs. 55.48 ± 16.57, P = 0.002) and showed intergenotypic variation in the CAD patients.Conclusion:Our study indicated that reduced NO levels and eNOS T-786C genetic polymorphism are significant risk factors for the development and severity of CAD in the Iranian population.

Genetic Contributions to Childhood Obesity: Association of Candidate Gene Polymorphisms and Overweight/Obesity in Korean Preschool Children.

This study was aimed to investigate the association of candidate gene polymorphisms and obesity or overweight in young Korean children. A total of 190 Korean preschool children (96 control, 48 overweight, and 46 obese children) were genotyped for the angiotensin converting enzyme (ACE) insertion (I)/deletion (D), angiotensin II type 2 receptor (AT2) C3123A, transforming growth factor (TGF)-β1 T869C, vascular endothelial growth factor (VEGF) T460C, and tumor necrosis factor (TNF)-α G308A polymorphisms. No differences were found among the groups with respect to age, sex, birth weight, blood pressure levels, and serum concentrations of glucose and total cholesterol. Obese children showed a higher incidence of ACE DD genotype and D allelic frequency compared to the controls (odds ratio [OR], 2.7, 95% confidence interval [CI], 1.01–7.21; OR, 2.5, 95% CI, 1.49–4.19; all P < 0.05). The frequency of TC genotype and C allele in the TGF-β1 T869C polymorphism (OR, 2.08, 95% CI, 1.01–4.27; OR, 1.93, 95% CI, 1.15–3.21) and that in the VEGF T460C polymorphism (OR, 2.5, 95% CI, 1.19–5.28; OR, 2.15, 95% CI, 1.26–3.68) was also higher in obese children than in control subjects (all P < 0.05). Overweight children exhibited a higher frequency of the A allele in the AT2 C3123A polymorphism compared to the controls (OR, 1.72, 95% CI, 1.03–2.88, P < 0.05). There were no differences in the TNF-α G308A polymorphism among the groups. The ACE I/D, AT2 C3123A, TGF-β1 T869C, and VEGF T460C polymorphisms can affect susceptibility to obesity or overweight in Korean children.

The Influence of C936T Gene in Wild of the Vascular Endothelial Growth Factor and Biochemical Variants Analysis for Alpha-Fetoprotein in Hepatocellular Carcinoma Patients in Egypt

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors. It is important to detect disease and recurrence at its earlier period. The aim of this study was to evaluate the influence of the C936T polymorphism of the VEGF and Alfa feto-Protein (AFP) on Hepatocellular carcinoma (HCC), Hepatitis C Virus (HCV) and control groups. Also, estimation of serum AFP and correlation with other parameters was studied. In this study was included 75 subjects, 25 patients with HCV, 25 patients with confirmed HCC and 25 healthy volunteers were subjected to abdominal ultrasonography, AFP and VEGF were assessed. The statistical analysis will include the Fisher exact test, T test and the multivariate regression, with significance level P<0.05 (AU). The result has showed that Serum level of AFP was significantly higher in HCC group when compared with control group and There was a nonsignificant increase in serum (AFP) level in the untreated HCV infected group compared to control group and also there was a nonsignificant increase in serum (AFP) activity in the HCC group compared to untreated HCV infected group with a (P value = 0.203). the influence of the C936T polymorphism of the VEGF distribution of the studied groups showing that Positive gene have higher incidence of HCV and HCC infection than Negative gene, when compared to control group. Sensitivity and specificity of markers in diagnosis of HCC were 52% and 40% respectively for AFP using a cutoff value of 3.39 ng/ml. VEGF may be useful marker for detection of HCC in addition to traditional markers.

T-786C variation in the promoter sequence of human eNOS gene markedly influences its expression level.

This study investigated the role of the T-786C polymorphism (SNP) in the 5'-flanking sequence of the endothelial nitric oxide synthase gene (eNOS) on its expression level in vascular endothelium with the ultimate goal of shedding more light on the mechanisms by which genetic variations of eNOS might affect the vascular level of nitric oxide (NO). Sequences in the 5'-flanking region of eNOS gene were PCR-amplified using genomic DNA templates isolated from blood samples collected from cardiovascular disease (CVD) patients. Two sequence-versions carrying the same SNP site were used; a short (345 bp) and an extended one (1,594 bp), numbered relative to the translational start site. All sequences were cloned into a promoter-less vector (pGL3-basic), which carries the firefly luciferase gene as a reporter. Genotyping of the T-786C polymorphism was performed using Sanger sequencing of the insert region. Luminescence levels were then recorded 24-48 h after transfecting human endothelial cell line (EA.hy926). Three genotypes were identified in the subject samples; TT, TC, or CC. The highest expression levels associated with the TT genotype, followed by the TC genotype, then the CC genotype. The extended sequence version produced higher expression levels compared to the shorter version. Our results provide evidence that the T allele at the T-786C SNP site of the eNOS gene results in increased expression of the enzyme, and consequently might provide a protective mechanism from CVD. The extended promoter sequence of eNOS resulted in higher expression of the gene, suggesting the presence of some essential binding sites for transcription enhancing proteins.

Association between endothelial nitric oxide synthase gene polymorphisms and risk of ischemic stroke: A meta-analysis.

Previously published studies that have examined whether the three polymorphisms, G894T, T786C, and 4b/a in the endothelial nitric oxide synthase (eNOS) gene, are associated with ischemic stroke (IS) have reported conflicting results. Thus, we performed a meta-analysis to examine the potential association between these three single nucleotide polymorphisms (SNPs) of the eNOS gene and IS risk. A literature search was carried out for eligible candidate gene studies published before August 05, 2015 in the PubMed, Embase, and Google Scholar databases. The following combinations of main keywords were used in our study: ('endothelial nitric oxide synthase') or ('eNOS') and ('G894T, 4b/a, and T786C') and ('polymorphism') or ('polymorphisms') and ('Ischemic Stroke' or 'IS') and ('Cerebral Infarction' or 'CI') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using fixed or random effects model. Meta-regression analysis was used to investigate the potential sources of heterogeneity. Begg's funnel plots were used to explore the publication bias, and heterogeneity was assessed by I2 test. Twenty seven case-control studies involving 6733 cases and 7305 controls were analyzed in our meta-analysis. Significant association was observed for G894T (OR = 1.17; 95% CI: 1.08 to 1.28; P< 0.001) and 4b/a (OR = 1.25; 95% CI: 1.13 to 1.39; P < 0.001) whereas a non-significant association was observed for T786C (OR = 1.11; 95% CI: 0.98 to 1.26; P =0.109) eNOS gene polymorphisms and IS. Our meta-analysis establishes that the G894T and 4b/a polymorphisms of eNOS gene are significantly associated with the risk of IS. However, a non-significant association was found between T786C polymorphism of the eNOS gene and IS risk. Further prospective large epidemiological studies need to be done to confirm these findings.

GENOTYPE -786CC OF THE ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE NOS3 AS A FACTOR OF ADVERSE CORONARY HEART DISEASE COURSE AND INCREASED ON-TREATMENT PLATELET AGGREGATION

Aim. To assess the associations of polymorphism T-786C gene NOS3 with the severity of clinical course of coronary heart disease (CHD) and platelet aggregatability in the selection of patients receiving clopidogrel and acetylsalicylic acid (ASA) compounds after selective coronary intervention. Material and methods. In the study, 203 CHD males included, taking ASA and clopidogrel as double antiplatelet therapy for coronary intervention. The test performed, of induced platelet aggregation with adenosine diphosphate (ADP) (2,5 mcM and 5,0 mcM) and epinephrine (0,2 mcM). Genotyping was done with the allele specific polymerase chain reaction (“SNP-express”, SPF Litekh, Russia). Statistics was done with Mann-Whitney test, Kruskal-Wallis test and Pearson chisquare or bi-test by Fisher. Differences were taken as significant at p<0,05. Results. In the studied group, genotypes -786TT, -786TC, -786CC were found with the prevalences 72 (35,4%), 99 (48,8%), 32 (15,8%), respectively. For the carriers of -786CC there was found highest grade of platelet aggregation with ADP 2,5 mcM (p=0,047) and with epinephrine (p=0,008). Carriers of -786TC had the highest left ventricle ejection fraction (p=0,035). Conclusion. In the selection of CHD males taking ASA and clopidogrel, carriage of -786CC polymorphism T-786C gene NOS3 was related to higher platelet aggregation in response to ADP and epinephrine. For these patients, the carriage of genotype -786CC gene NOS3 might be a predictor of thrombotic complications after coronary stenting and more adverse outcome of CHD.

Polymorphisms of TGFβ1T+869C and C-509T with Lung Cancer Risk: A Meta-analysis.

Lung cancer is the most common malignancy worldwide. A better understanding of the mechanisms may contribute to early diagnosis and establishment of new therapeutic targets. A meta-analysis was performed to investigate the association of transforming growth factor-beta 1 (TGFβ1) T+869C and C-509T polymorphisms with lung cancer susceptibility. Relevant studies were identified through PubMed, Medline, Embase and CNKI databases. The pooled odds ratios (ORs) with its 95% confidence intervals (CIs) were employed to assess these associations in a fixedor random-effects model. For the TGFβ1 T+869C polymorphism, 5 published case-control studies with 1167 cases and 1365 controls were included. Overall, no significant association was found between the TGFβ1 T+869C polymorphism and lung cancer susceptibility under any genetic models in the total population (p > 0.05). A subgroup analysis by ethnicity showed no significant association among the Asian population as well, while a significant association was observed in Caucasian descendants. For the TGFβ1 C-509T polymorphism, 4 studies were considered, including 1029 cases and 1133 controls. However, this polymorphism also did not increase the risk of lung cancer in all genetic comparison models. This meta-analysis suggests that TGFβ1 T+869C and C-509T polymorphisms may not contribute to lung cancer risk in the total population, while the T+869C polymorphism may increase the risk of lung cancer in the Caucasian population. However, many studies are still required to evaluate these associations in large populations.