Association of Glu298Asp Polymorphism of eNOS Gene with Cardiovascular Diseases

Molecular-genetic diagnostics of polygenic diseases is a new and interesting area in laboratory diagnostics, especially in the area of cardiovascular diseases, as one of the leading causes of mortality in the world population. Aims: The aim of the paper was to analyse variants of the endothelial nitric oxide synthase gene (NOS3) (Glu298Asp/G894T) in the human population of Tuzla Canton in relation to cardiovascular diseases. Study Design: The study included 112 respondents of both sexes over 18 years old. The experimental group for the analysis of the polymorphism (Glu298Asp) of the endothelial nitric oxide synthase gene included 56 respondents of both sexes with cardiovascular disease (hypertension), while the control group comprised 56 healthy respondents of both sexes without a prior history of cardiovascular disease (sample/control). Place and Duration of Study: Blood sampling was performed at Medical Center "Plava Poliklinika", “Plava Medical Group”, Department of Biochemistry, Microbiology and Genetics, Tuzla. DNA isolation and molecular-genetic analysis of the samples were performed in Laboratory for scientific research at the Department of Biology, Faculty of Natural Sciences and Mathematics in Tuzla. Methodology: The genotyping of eNOS Glu298Asp polymorphism for all respondents was determined by an optimized method based on PCR-RFLP reaction. Results: In the total sample of respondents, the highest genotype frequencies of the eNOS gene were recorded for the GG genotype (53.5%) and the GT genotype (35.7%). The lowest frequency was recorded for the TT genotype, which was 10.8%. Conclusion: The results obtained in the study provide good guidelines for further study of a molecular-genetic association between a high number of gene candidates and cardiovascular diseases, which will contribute to the incorporation of these results into the existing regional and European genetic database.

Polimorfismo da região codante do gene NOS3 em idosos com Síndrome Metabólica / Polymorphism of the codante region of the NOS3 gene in the elderly with Metabolic Syndrome / Polimorfismo de la región codante del gen NOS3 en ancianos con Síndrome Metabólico

Objetivo: O presente estudo analisou se a presença do polimorfismo VNTR localizado no íntron 4 do gene NOS3 na região codante difere nos pacientes com Síndrome Metabólica e portadores de Hipertensão Arterial e/ou Diabetes Mellitus dos controles normotensos. Método: Neste estudo caso-controle, foi executada a técnica de PCR para identificar a presença dos genótipos em 94 pacientes idosas residentes do Distrito Federal. As associações com as manifestações clínicas foram feitas no programa SPSS. Foi analisada a probabilidade de equilíbrio de Hardy-Weinberg e Odds Ratio, considerando um intervalo de confiança de 95% e nível de significância de 5%. Resultados: Verificou-se que das 94 pacientes, 71 evidenciaram a presença de hipertensão e 23 a ausência da doença, o valor de p obtido foi de 0,218. Em relação a Diabetes Mellitus, 49 idosas possuem o problema e 45 não possuem, o valor de p obtido foi de 0,372. Conclusão: Não há associação entre os genótipos do polimorfismo do gene NOS3, e a manifestação de Hipertensão Arterial e Diabetes Mellitus em idosas portadoras da SM.

Objective: The present study analyzed whether the presence of VNTR polymorphism located in intron 4 of the NOS3 gene in the codante region differs in patients with Metabolic Syndrome and patients with Hypertension and/or Diabetes Mellitus from normotensive controls. Method: In this case-control study, the PCR technique was performed to identify the presence of genotypes in 94 elderly patients living in the Federal District. Associations with clinical manifestations were made in the SPSS program. The probability of Hardy-Weinberg equilibrium and Odds Ratio was analyzed, considering a confidence interval of 95% and significance level of 5%. Results: we found that of the 94 patients, 71 showed the presence of hypertension and 23 the absence of the disease, the p-value obtained was 0.218. Regarding Diabetes Mellitus, 49 old women have the problem and 45 do not have the p value obtained was 0.372. Conclusion: There is no association between nos3 gene polymorphism genotypes, and the manifestation of Arterial Hypertension and Diabetes Mellitus in elderly patients with MS.

Objetivo El presente estudio analizó si la presencia de polimorfismo VNTR localizado en el intrón 4 del gen NOS3 en la región codante difiere en pacientes con Síndrome Metabólico y pacientes con Hipertensión y/o Diabetes Mellitus de controles normotensos. Método: En este estudio de casos y controles, se realizó la técnica de PCR para identificar la presencia de genotipos en 94 pacientes ancianos residentes en el Distrito Federal. Las asociaciones con manifestaciones clínicas se realizaron en el programa SPSS. Se analizó la probabilidad de equilibrio de Hardy-Weinberg y Odds Ratio, considerando un intervalo de confianza del 95% y un nivel de significancia del 5%. Resultados: Se encontró que de los 94 pacientes, 71 mostraron la presencia de hipertensión arterial y 23 la ausencia de la enfermedad, el valor de p obtenido fue de 0,218. En cuanto a la Diabetes Mellitus, 49 ancianas tienen el problema y 45 no tienen el valor de p obtenido fue de 0,372. Conclusión: No existe asociación entre los genotipos de polimorfismo del gen nos3 y la manifestación de Hipertensión Arterial y Diabetes Mellitus en pacientes ancianos con SM

The Polymorphism of Regulatory Region of NOS3 Gene (rs2070744, Genotype CC) Protect Patients from Chronic Migraine.

Aims: There is evidence that endothelial nitric oxide synthase has a role in migraine pathophysiology. In our research, the role of SNP rs2070744 (c.-813C>T) in promoter region of NOS3 gene in the episodic and chronic forms of migraine is considered. Place and Duration of Study: University Headache Clinic between June 2012 and November 2014 and Department of Genetics, Faculty of Biology of Lomonosov Moscow State University between October 2013 and March 2016. Methodology: The study included 138 patients with migraine (44 with chronic and 96 with episodic migraine). The control group included 348 unexamined subjects. Genotypes were determined using real-time PCR with allelic discrimination test. Statistical processing was performed using Fisher test and Pearson's chi-squared test. Results: Our study evaluated the link of CC genotype of rs2070744 with migraine (Fisher’s p=0.026) and episodic migraine (Fisher’s p=0.022). Conclusion: Genotype CC of SNP rs2070744 in the regulatory region of NOS3 gene is more specific for episodic migraine and may prevents the chronification of migraine.

Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

A Meta analysis on NOS3 G894T polymorphism and cancer susceptibility / 重庆医学

Objective To investigate the relation between polymorphism of NOS3 G894T and susceptibility of cancer .Methods Literatures under the inclusion and exclusion criteria about relation between polymorphism of NOS 3 G894T and susceptibility of cancer were collected by computer -based retrieval and manual retrieval .The pools ORs with 95% CI were calculated to assess the association strength between polymorphism of NOS 3 G894T and cancer risk by Meta methods .Sensitivity and publication bias were evaluated .Results 19 literatures with 7679 cases of cancer and 8180 cases as control group were included .The pooled result indica-ted that no significant association between its polymorphism and cancer (ORT versus G=1 .030 ,95% CI=0 .964 -1 .101 ;ORTT versus GG=1 .056 ,95% CI=0 .895-1 .245 ;ORTG versus GG=1 .045 ,95% CI=0 .977-1 .119 ;ORTT/TG versus GG=1 .047 , 95% CI=0 .981-1 .117 ;ORTT versus TG/GG=1 .005 ,95% CI=0 .900-1 .123) .No significant association was observed in sub-group analysis based on ethnicity ,cancer type ,and source of control group .Conclusion There was no relationship between NOS3 G894T polymorphism and cancer susceptibility .

Association between 894G>T endothelial nitric oxide synthase gene polymorphisms and metabolic syndrome / Associação entre o polimorfismo 894g>T do gene óxido nítrico sintetase endotelial e síndrome metabólica

Metabolic syndrome (MS) is a cluster of cardiovascular risk factors such as hypertension, dyslipidemia, obesity and type II diabetes. Here, we performed a case-control study analyzing the association between 894G>T endothelial nitric oxide synthase gene polymorphism (NOS3) and MS in 616 subjects. Genotype frequencies were TT= 9.3 percent, GG= 37.2 and TG= 53.6 percent and the allelic frequencies were T=0.36 and G= 0.64. We observed a higher TT genotype frequency in the male MS group than control subjects (p=0.02), independent of other variables. We found an association between hypertension and TT genotype in females. Our data suggests that 894G>T plays a significant role in the mechanistic interaction between metabolic risk such as hypertension and MS, although sex-related differences may exist.

A síndrome metabólica (SM) é um agrupamento de fatores de riscos cardiovasculares, tais como hipertensão, dislipidemia, obesidade e diabetes tipo 2. Realizou-se um estudo caso-controle para analisar a associação entre o polimorfismo (894G>T do gene da enzima endotelial oxido nítrico sintetase (NOS3) e a SM em 616 voluntários. As freqüências genotípicas foram: TT = 9,3 por cento, GG = 37,2 por cento e TG = 53,6 por cento, e as freqüências alélicas T = 0,36 e G = 0,64. Observou-se freqüência mais alta do genótipo TT em homens com SM do que nos controles, independentemente de outros fatores (p = 0,02). Também observou-se associação entre hipertensão e o genótipo TT nas mulheres. Os dados do estudo sugerem que o polimorfismo 894G>T pode ter papel significativo na interação entre riscos metabólicos, tais como a hipertensão e a SM, ainda que existam diferenças relacionadas ao sexo.

Expression Pattern of Nitric Oxide Synthases in Rat Skeletal Muscle after Cyclic Episodes of Short Ischemia and Reperfusion / 체질인류학회지

The ischemic preconditioning was initially identified as a protective maneuver induced by brief periods of ischemia followed by reperfusion. Although ischemic preconditioning can reduce ischemic injury of heart, skeletal muscle and neuronal tissue, it's protective mechanism remains elusive. Recently, several investigations suggest the associations of nitric oxide with protection from ischemic injury. Nitric oxide synthesized by a member of nitric oxide synthase (NOS) family has been known to increase or decrease the ischemic injury. The purpose of this study was to observe the expression patterns of NOS 1, NOS 2 and NOS 3 in the rat skeletal muscle after cyclic episodes of short ischemia and reperfusion. Nine and thirty-five weeks-old male Sprague-Dawley rats were divided into control and cyclic short ischemia and reperfusion groups. The experimental group was further divided into 3 groups based on cycles of short ischemia and reperfusion. For cyclic short ischemia and reperfusion, left commom iliac artery was occluded 3, 6 and 10 times for 5 minutes ischemia followed by 5 minutes reperfusion using rodent vascular clamps. The animals were sacrificed at hours 0, 3, 6, 24 and 72 after reperfusion and the left rectus femoris muscles were removed. The expression profiles and distribution of NOS 1, NOS 2 and NOS 3 were examined with immunohistochemical staining. The results were as follows; In the cyclic of short ischemia and reperfusion groups, the mortality was increased with increasing of cyclic episodes at 72 hours after reperfusion, and aging. In the control group, NOS 1, NOS 2 and NOS 3 immunoreactivities showed no differenes with aging. In the 9 weeks-old rats, NOS 1 immunoreactivities were observed moderate at 24 hours after 6 times of short ischemia and reperfusion, and moderate and strong at 24 hours after 10 times of short ischemia and reperfusion. In the 35 weeks-old rats, NOS 1 immunoreactivities were observed trace or mild at 24 hours after 6 and 10 times of short ischemia and reperfusion. At 3 hours after 3 times of short ischemia and reperfusion, NOS 2 immunoreactivities were observed moderate or strong, and trace in the 9 and 35 weeks-old rats, respectively. At 3 hours after 10 times of short ischemia and reperfusion, NOS 3 immunoreactivities were observed mild or moderate, and trace or negative in the 9 and 35 weeks-old rats, respectively. In summary, the expression profile of NOS 1, NOS 2 and NOS 3 were observed differently with increasing episodes of short ischemia and reperfusion. The alteration was the most prominent in NOS 3 than in NOS 1 and NOS 2. These results suggest that the alteration of NOS 3 known to protect tissue against ischemic injury may be associated with increasing mortality after multiple episodes of short ischemia and reperfusion.

Expressions of NOS2 and NOS3 in human non-small cell lung cancer and the relationship with tumor angiogenesis and lymph node metastasis / 医学研究生学报

Objective: To investigate the expression and distribution of NOS2 and NOS3 in human non-small cell lung cancer (NSCLC),and to evaluate the relationship between their expression and tumor angiogenesis and lymph node metastasis. Methods: the expression of NOS2, NOS3 and IMVD in 95 patients with NSCLC were examined using immunohistochemical methods (S-P), and the relationship between them and many clinicopathological parameters was analyzed. Results: The positive expression of NOS3 was associated with histological subtype, IMVD and lymph node metastases of NSCLC(P

Expressions of VEGF, b-FGF,NOS_2 and NOS_3 in human non-small cell lung cancer and the relationship between them and tumor angiogenesis and lymph node metastasis / 中国癌症杂志

Purpose:To investigate the expression and distribution of VEGF, b FGF, NOS 2 and NOS 3 in human non small cell lung cancer (NSCLC),and to evaluate the relationship between their expression and tumor angiogenesis and lymph node metastasis.Methods:The expression of VEGF, b FGF, NOS 2, NOS 3 and IMVD in 95 patients with NSCLC were examined using immunohistochemical methods (SP), and the relationship between them and many clinicopathological parameters was analyzed.Results:The positive expression of VEGF and b FGF was associated with intratumor microvessel density(IMVD), TNM stage and lymph node metastases of NSCLC, respectively( P

Effect of insulin on expression of VEGF receptor (flt-1、flk-1/KDR) protein in serum-free cultured bovine thoracic aortic endothelial cells and its relation to the NOS_3 activation of endothelium / 中国介入心脏病学杂志

0 05) between the insulin incubation groups both with and without L NAME incubations Conclusion Insulin has no direct effect on the expression of VEGF receptor (flt 1? flk 1/KDR) protein in bovine thoracic aortic endothelial cells The NOS 3 activation of endothelium is not the main cause that could affect the expression of VEGF receptor (flt 1?flk 1/KDR) protein of endothelium