Glu298Asp Polymorphism Of eNOS Gene Research Articles

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.

ENOS gene Glu298Asp variant confer risk in sudden sensorineural hearing loss

Background: Sudden sensorineural hearing loss (SSNHL) causes the loss of hearing of 30 dB or greater on at least three contiguous frequencies. It is known to be a multifactorial disease which the exact cause is unknown, rendering it as an idiopathic disorder of patients.Aims/objectives: This study aims to shed further light on pathogenesis of this disease by studying the association between eNOS gene Glu298Asp polymorphism and VDR gene FokI polymorphism with SSNHL in Iranian population.Material and methods: This study involves a total of 77 cases and 100 controls, with patients inflicted with SSNHL categorized in case group and healthy subjects as control group. Genotyping of the VDR and eNOS genes was conducted by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.Results: Our results showed a statistically significant association between genotype frequencies of eNOS gene Glu298Asp polymorphism in case group compared to healthy individuals in the control group (p = .01). Also, TT genotype was significantly the most prevalent genotype in case group in comparison to control group (TT vs GT + GG, OR = 3.5; 95% CI = 1.18–11.79). On the other hand, analysis of VDR gene FokI polymorphism frequencies showed no statistically significant association with SSNHL.Conclusions and significance: Our findings showed a significant association between the eNOS gene Glu298Asp polymorphism and SSNHL in the Iranian population; and “TT” genotype might be considered as a risk factor for SSNHL.

Prevalence of common polymorphisms of AT-rich interaction domain 1A and endothelial nitric oxide synthase in patients with endometriosis compared to control group

Introduction: Endometriosis is a common gynecologic disorder defined as ectopic presence of endometrial tissue in extrauterine sites. Endometriosis is associated with infertility and risk of malignancy. Identification of genetic factors responsible for development and malignant transformation of endometriosis can improve therapeutic approaches. In this study, we investigated the association of AT-rich interaction domain 1A ( ARID1A) and endothelial nitric oxide synthase ( eNOS) polymorphisms with endometriosis and staging of the disease. Methods: A total of 100 women with laparoscopy-confirmed diagnosis of endometriosis were included and compared with 100 women without endometriosis as the control group. Genotypes of patients regarding Gln920Ter polymorphism of ARID1A gene and Glu298Asp polymorphism of eNOS gene were determined by polymerase chain reaction techniques on blood samples from the study population. The prevalence of each genotype in endometriosis patients was compared with healthy controls using the chi-square test. Results: Significantly higher prevalence of non-CC genotype for ARID1A Gln920Ter polymorphism and non-GG genotype for G894T polymorphism of the eNOS gene was detected in the endometriosis group. There was no significant relationship between these polymorphisms and staging of endometriosis. Discussion: Significant variation of prevalence of Gln920Ter polymorphism of the ARID1A gene and Glu298Asp polymorphism of the eNOS gene among the two groups can indicate a causative effect of these genetic alterations on the development of endometriosis.

Lack of role of endothelial nitric oxide synthase gene Glu298Asp polymorphism in rheumatoid arthritis among Asian Indians

Aim: The aim of this study was to investigate the association of Glu298Asp polymorphism in the endothelial nitric oxide synthase (eNOS) gene with rheumatoid arthritis (RA) in Asian Indians. Methods: We conducted a case control study in which 100 patients diagnosed with RA and 100 healthy controls were enrolled. DNA was extracted from peripheral blood and eNOS polymorphism was detected by PCR-RFLP. Plasma samples from the subjects were screened for nitric oxide (NO). Results: There was a trend of increase of GG genotypic and G allelic frequencies of the eNOS gene Glu298Asp in patients when compared with controls. GT genotype emerged as major genotype in both controls and patients. Genotypes disobeyed Hardy-Weinberg equilibrium. Reduced NO levels was detected in patients as compared to controls. Patients with GG genotype and GT genotypes were found to have significantly low level of plasma NO as compared to controls with GG and GT genotypes. Conclusions: eNOS gene Glu298Asp polymorphism is not associated with the susceptibility of rheumatoid arthritis in Asian Indians.

Association of endothelial nitric oxide synthase gene polymorphisms with classical risk factors in development of premature coronary artery disease

Genetic polymorphism of the endothelial nitric oxide synthase (eNOS) affects the pathogenesis of atherosclerosis and associated with premature coronary artery disease (PCAD). We aimed to explore the association between Glu298Asp polymorphism of the eNOS gene and premature CAD in Egyptians, and the possible interaction between this polymorphism and other risk factors. The study population consisted of 116 patients with PCAD, and 119 controls. Glu298Asp polymorphism (rs1799983) of the eNOS gene was analyzed by polymerase chain reaction (PCR). We found that the TT genotype of the eNOS gene increased the risk of PCAD by 2.6. Hypertension, diabetes, smoking, total cholesterol, triglycerides, LDLc, HDLc and TT genotype of the eNOS gene were independent risk factors for the development of PCAD. We conclude that, the TT genotype of Glu298Asp polymorphism of eNOS gene is an independent risk factor of PCAD in Egyptians. The association of smoking, obesity, dyslipidemia and/or metabolic syndrome with the TT genotype increased the risk of the development of PCAD.

ASSOCIATION OF CLINICAL AND GENETIC FACTORS WITH LEFT VENTRICLE HYPERTROPHY IN ARTERIAL HYPERTENSION

Aim. To evaluate association of clinical and genetic factors with left ventricle hypertrophy (LVH) in patients with arterial hypertension (HT). Materials and methods. 672 patients with HT were involved, aged 50,6 y.o. in average, men 67%. Laboratory assays, ECG, echocardiography were performed. Control group included 184 healthy per???sons. Genotyping with single-nucleotide substitutions of the endothelial NO synthase (eNOS) Glu298Asp gene, the C242T of the NADPH oxidase p22phox subunit and the angiotensin 2 receptor type 1 А1166С gene was carried out using a polymerase chain reaction (PCR) with evaluating of restriction fragments length polymorphism, while with substitutions of the angiotensinogen М235Т, G(-6)A gene allele-specific PCR “in real time” was applied. Results. LVH was found in 39% of patients. It was more frequent in persons above 50 years old (OR 2,8, р<0,0001), in men (OR 1,43, p=0,035), in HT of degree 2-3 (OR 3,35, р<0,0001), HT duration more than 5 years (OR 2,52, р<0,05), in obesity (OR 1,57, р=0,005) or diabetes (OR 3,33, р<0,0001) presence. At genetic factors evaluation decrease of LVH risk was revealed in persons with the MM polymorphism of the angiotensinogen М235Т gene (OR 0,506, р=0,0187). Association of the MM genotype with LVH risk lowering was more obvious at the young age (OR 0,31, р=0,018). The A allele of the eNOS gene Glu298Asp polymorphism increased risk of LVH development when HT was diagnosed in the young age (OR 1,98, р=0,037) and in women up to 50 years old (OR 2,34, р=0,027). The T allele of the p22phox NADPH oxidase gene С242Т polymorphism correlated with LVH risk reduction in HT patients up to 50 years old (OR 0,6, p=0,01), the C allele – with increase of it (OR 1,66, р=0,01), this influence was more noticeable in women up to 50 years old (T allele – OR 0,21; C allele – OR 4,57, p=0,001). Conclusion. Hypertensive LVH correlates with age, male gender, HT degree and duration, obesity and diabetes mellitus. Genetic factors were less associated with LVH.

Endothelial nitric oxide synthase gene polymorphism is associated with Behçet's disease in Tunisian population

Nitric oxide (NO) is a molecule that plays a key role in many physiologic and pathologic processes. It is produced in vivo from the aminoacid l-arginine by a family of nitric oxide synthases (NOS). Endothelial NOS (eNOS) is a constitutively expressed isoform of NOS. The eNOS gene entails several polymorphisms, of which certain were investigated in Behçet's disease (BD). We sought to establish the association of eNOS gene Glu298Asp polymorphism in exon 7 with susceptibility to BD. In this study, 135 Tunisian patients with BD and 157 healthy blood donor controls from the same geographic area were genotyped by polymerase chain reaction technique for eNOS polymorphism in exon 7. Our results showed that the distribution of the Glu298Asp genotype differed between BD patients and controls but did not reach statistical significance (p = 0.06). Allele Asp298 was significantly more frequent in healthy controls than in BD patients (p = 0.037, chi(2) = 4.33, OR = 1.01, 95% CI = 1.41-1.99). A significant difference was found (p = 0.004, OR = 1.26, 95% CI = 2.13-3.62) between BD patients with skin lesions and patients without this manifestation. Our findings suggest that Glu298Asp polymorphism of eNOS gene is associated with BD susceptibility as well as skin lesions.

Endothelial nitric oxide synthase gene polymorphism (Glu298Asp) and development of pre-eclampsia: a case-control study and a meta-analysis

BackgroundPre-eclampsia is thought to have an important genetic component. Recently, pre-eclampsia has been associated in some studies with carriage of a common eNOS gene Glu298Asp polymorphism, a variant that leads to the replacement of glutamic acid by aspartic acid at codon 298.MethodHealthy women with singleton pregnancies were recruited from 7 district general hospitals in London, UK. Women at high risk of pre-eclampsia were screened by uterine artery Doppler velocimetry at 22–24 weeks of gestation and maternal blood was obtained to genotype the eNOS Glu298Asp polymorphism. Odds ratios (OR) and 95%CI, using logistic regression methods, were obtained to evaluate the association between the Glu298Asp polymorphism and pre-eclampsia. A meta-analysis was then undertaken of all published studies up to November 2005 examining the association of eNOS Glu298Asp genotype and pre-eclampsia.Results89 women with pre-eclampsia and 349 controls were included in the new study. The Glu298Asp polymorphism in a recessive model was not significantly associated with pre-eclampsia (adjusted-OR: 0.83 [95%CI: 0.30–2.25]; p = 0.7). In the meta-analysis, under a recessive genetic model (1129 cases & 2384 controls) women homozygous for the Asp298 allele were not at significantly increased risk of pre-eclampsia (OR: 1.28 [95%CI: 0.76–2.16]; p = 0.34). A dominant model (1334 cases & 2894 controls) was associated with no increase of risk of pre-eclampsia for women carriers of the Asp298 allele (OR: 1.12 [95%CI: 0.84–1.49]; p = 0.42).ConclusionFrom the data currently available, the eNOS Glu298Asp polymorphism is not associated with a significant increased risk of pre-eclampsia. However, published studies have been underpowered, much larger studies are needed to confirm or refute a realistic genotypic risk of disease, but which might contribute to many cases of pre-eclampsia in the population.