Association of Common Variants in eNOS Gene with Primary Open Angle Glaucoma: A Meta-Analysis.
ABSTRACT: Purpose. To clarify the association of endothelial nitric oxide synthase (eNOS) polymorphisms and primary open angle glaucoma (POAG). Methods. After a systematic literature search in the MEDLINE, EMBASE, and ISI Web of Science databases, all relevant studies evaluating the association between the polymorphisms (rs2070744 and rs1799983) of eNOS gene and POAG were screened and included. The pooled odds ratios (ORs) and the 95% confidence interval (CI) of each single-nucleotide polymorphism (SNP) in five genetic models were estimated using fixed-effect model if I (2) < 50% in the test for heterogeneity; otherwise the random-effects model was used. Results. Thirty-one records were obtained, with five being suitable for meta-analysis. The overall results showed that both TT genotype in rs2070744 and GG genotype in rs1799983 are associated with decreased risk of POAG susceptibility. Stratified analysis based on ethnicity showed that the association of rs2070744 with POAG remained only in Caucasians. Results of subgroup analysis by sex indicated association between both polymorphisms and POAG in female group, but not in male group. Conclusions. TT genotype and/or T-allele in rs2070744, as well as GG genotype and/or G-allele in rs1799983, was associated with decreased risk for POAG overall and in female group.
Project description:Background:Physiological pathways such as bradykinin, renin-angiotensin, neurohormones and nitric oxide have been shown to play an important role in the regulation of cardiovascular function. Genetic variants of these pathways may impact blood pressure and left ventricular (LV) mass in different populations. To evaluate associations of genetic polymorphisms of bradykinin B2 receptor (BDKRB2), alpha-adrenergic receptors (ADRA) and endothelial nitric oxide synthase (eNOS) on the modulation of the blood pressure and the left ventricular mass. Methods:We enrolled 758 individuals without overt heart disease. Blood pressure was estimated by auscultatory method during the clinical examination. Left ventricular (LV) mass was assessed by echocardiography. Genotypes for ADRA1A rs1048101, ADRA2A rs553668, ADRA2B rs28365031, eNOS rs2070744, eNOS rs1799983, and BDKRB2 rs5810761 polymorphisms were assessed by high-resolution melting analysis. Results:BDKRB2 polymorphism rs5810761 was associated with blood pressure. Carriers of DD genotype had higher levels of SBP and DBP than carrier of II genotype (p?=?0.013 and p?=?0.007, respectively). eNOS polymorphism rs1799983 was associated with DBP. Carriers of GT genotype had lower levels of DBP than carriers of GG genotype (p?=?0.018). eNOS polymorphism rs2070744 was associated with LV mass. Carriers of TC genotype had higher LV mass than carriers of TT genotype (p?=?0.028). Conclusions:In a cohort of individuals without overt heart disease, the BDKRB2 rs5810761 polymorphism (DD genotype carriers) were associated higher systolic and diastolic blood pressures, and the eNOS rs1799983 polymorphism (T allele carriers) were associated with lower diastolic blood pressure. The eNOS rs2070744 polymorphism (C allele carriers) was associated with higher left ventricular mass. These data suggest that eNOS and bradykinin receptor genetic variants may be potential markers of common cardiovascular phenotypes.
Project description:AIM:To investigate the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms in patients with primary open-angle glaucoma (POAG) of Saudi origin. METHODS:This case-control study included 173 patients with POAG (94 men and 79 women) and 171 controls (98 men and 73 women). Genotyping of rs2070744 (T-786C) and rs1799983 (G894T) variants of the NOS3 gene was performed using TaqMan® assay. RESULTS:Rs1799983 genotypes showed a significant association with POAG but did not survive Bonferroni correction (pcorrection = 0.01). The minor 'T' allele was significantly associated with the risk of POAG among men (p = 0.025, odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.07-2.94). Likewise, the genotypes were significantly associated with POAG among men in dominant (p = 0.030, OR = 1.92, 95% CI = 1.06-3.48) and log-additive models (p = 0.022, OR = 1.82, 95% CI = 1.08-3.07), and after adjustment for age and smoking. Genotype and allele frequencies of rs2070744 were not significantly different between POAG cases and controls, and after sex stratification. CG haplotype was significantly protective (p = 0.011, OR = 0.52, 95% CI = 0.32-0.87) and CT haplotype conferred significantly increased risk of POAG (p = 0.016, OR = 2.60, 95% CI = 1.16-5.82) among men. Rs1799983 showed trend (p = 0.054) towards risk of POAG independent of age, gender, smoking, and rs2070744 polymorphism in logistic regression analysis. Both the polymorphisms showed no association with POAG phenotypes such as intraocular pressure and cup/disc ratio. CONCLUSION:Our results suggest that the polymorphism rs1799983 and the haplotypes of rs20707440 and rs1799983 in the NOS3 gene may significantly modulate the risk of POAG in Saudi's, particularly among men. Further larger studies are needed to confirm these findings.
Project description:We aimed to identify specific polymorphisms of genes encoding for vascular endothelial growth factor A (VEGFA), endothelial nitric oxide synthase (eNOS), renin-angiotensin system (angiotensinogen gene [AGT], angiotensinogen type 1 receptor [AGTR1], angiotensin-converting enzyme [ACE]), and heme oxygenase-1 (HMOX-1) in a cohort of preterm infants and correlate their presence with the development of respiratory distress syndrome (RDS) requiring mechanical ventilation (MV), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP).We carried out a retrospective study to evaluate the allele frequency and genotype distribution of polymorphisms of VEGFA, eNOS, AGT, AGTR1, ACE, and HMOX-1 in a population of preterm neonates (n=342) with a gestational age ?28 weeks according to the presence or absence of RDS requiring MV, BPD, IVH, or ROP. Moreover, we evaluated through the haplotype reconstruction analysis whether combinations of the selected polymorphisms are related to the occurrence of RDS, BPD, IVH and ROP.In our population 157 infants developed RDS requiring MV, 71 BPD, 70 IVH, and 43 ROP. We found that TC+CC rs2070744 eNOS (41.7 vs. 25.4%, p=0.01) and GT+TT rs1799983 eNOS (51.8 vs. 35.2%, p=0.01) polymorphisms are independent risk factors for BPD. Haplotype reconstruction showed that haplotypes in VEGF and eNOS are significantly associated with different effects on RDS, BPD, IVH, and ROP in our population.We found that TC+CC rs2070744 eNOS and GT+TT rs1799983 eNOS polymorphisms are independent predictors of an increased risk of developing BPD. Haplotypes of VEGFA and eNOS may be independent protective or risk markers for prematurity complications.
Project description:BACKGROUND: Nitric oxide (NO) synthesized by endothelial cells is known to be a potent vasodilator. It has been suggested that polymorphisms in endothelial nitric oxide synthase (eNOS) can affect the response of the vascular endothelium to increased oxidative stress. The objective of the present study was to determine the presence of G894T (rs1799983), intron-4 (27-bp TR) and -T786C (rs2070744) polymorphisms in the eNOS gene among the Colombian general population. RESULTS: Genotype and allele frequencies showed significant differences in their distribution. White, black and mixed populations were in HW equilibrium for the variants in 27-bp TR- and rs1799983, but the black population was in HW disequilibrium for rs2070744 (p < 0.001). Allele "T" of rs1799983 polymorphisms was more common in the white population (26,5%) than the others, while allele "C" of rs2070744 polymorphisms had a similar frequency in all populations, and the allele 4a from 27-bp TR was more frequent in the black population (26,2%) than the others. Similar differences were found when genotypes were analyzed. CONCLUSION: The findings suggest that there is a substantial difference in the distribution of eNOS polymorphisms between different ethnic groups. These results could aid the understanding of inter-ethnic differences in NO bioavailability, cardiovascular risk, and response to drugs.
Project description:There are a number of susceptible factors for an increased risk of gastric cancer. Nitric oxide (NO) is considered to be associated with the development of a range of cancers. In particular, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) are known to play a central role in the production of NO. Published studies relating to the association between eNOS rs1799983, rs2070744, and iNOS rs2297518 polymorphisms and the risk of gastric cancer risk are conflicting and inconclusive and require further analysis.This study involved a meta-analysis of case-control studies relating to eNOS rs1799983, rs2070744, and iNOS rs2297518 polymorphisms published prior to January 2018. Literature searches were carried out in PubMed, Embase, Web of Science, the Cochrane Library databases, and the Chinese National Knowledge Infrastructure. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of association based on genotype data.A total of 1,356 cases and 1,791 controls were included from nine case-control studies involving eNOS rs1799983 (G894T), rs2070744 (T-786C), and iNOS rs2297518 (C150T) polymorphisms. Data analysis indicated that iNOS rs2297518 was a risk factor for Helicobacter pylorus-positive gastric cancer when compared with H. pylorus-negative gastric cancer (p=0.003, OR [95% CI] =2.19 [1.31-3.66]). In addition, the allelic, dominant, and recessive models of eNOS rs2070744 were significantly associated with a risk of gastric cancer (allelic model: p<0.00001, OR [95% CI] =0.23 [0.16-0.34]; dominant model: p<0.00001, OR [95% CI] =0.25 [0.15-0.42]; recessive model: p<0.00001, OR [95% CI] =0.16 [0.08-0.30]). No association was identified between eNOS rs1799983 and the risk of gastric cancer (p>0.05).iNOS rs2297518 and eNOS rs2070744 polymorphisms may represent susceptible factors for gastric cancer.
Project description:We investigated the phenotype-genotype association of the following endothelial nitric oxide synthase (eNOS) gene polymorphisms, rs743506, rs2070744, rs1799983, rs180079, rs3918226, rs207468799 and rs148554851, in patients suffering from migraine living in Edirne, Turkey. A total of 175 individuals, who had been diagnosed with migraine between April 2013 and December 2013, at the Neurology Department, Trakya University Medical Faculty, Edirne, Turkey, and 125 healthy controls were recruited. The above gene polymorphisms were analyzed from genomic DNA in both patient and control groups, using the pyro-sequencing method. The eNOS rs1799983 TT genotype frequency in migraine patients who had a headache duration of longer than 24 hours was statistically significantly higher than in patients who had migraine attacks that lasted under 24 hours (p = 0.047). In terms of the AGGTGGA haplotype, the severity of headache was statistically significant, and was found to be severe in 61.0% (p = 0.0001). Also in terms of the AGGTGGA haplotype, the duration of headache was statistically significant, and was >24 hours in 56.0% of patients (p = 0.008). In our study, there was no significant genotypephenotype relationship between eNOS rs743506, rs2070744, rs1799983, rs180079, rs3918226, rs207468799 and rs148554851 gene polymorphisms and migraine patients with and without aura living in Edirne, Turkey. The AGGTGGA haplotype constitutes a risk in terms of the severity and the duration of headaches in patients with migraine. This risk is significantly higher in patients with migraine with aura than patients with migraine without aura.
Project description:PURPOSE:To analyze the association of polymorphisms of the endothelial nitric oxide synthase (NOS3) gene and nitric oxide (NO) levels with high-tension primary open-angle glaucoma (POAG) in an Egyptian population. METHODS:This case-control study included 160 patients who had high-tension POAG (76 men and 84 women; age range 41-75 years) and 110 controls (56 men and 54 women; age range 55-78 years). Genotyping of T-786C (rs2070744), Glu298Asp (rs1799983), and the 27-bp insertional variable number tandem repeat (VNTR) in intron 4 of the NOS3 gene was performed with an amplification refractory mutation system PCR assay. The NO level was determined by measuring the total nitrate/nitrite (NOX) plasma level. RESULTS:The CC genotype of the T-786C polymorphism was significantly associated with POAG (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.26-5.13, p = 0.007). The C allele was significantly associated with POAG (OR = 1.86, 95% CI = 1.29-2.69, p<0.001). After stratification by sex, the CC genotype and the C allele were significantly associated with POAG in women only (OR = 3.06, 95% CI = 1.07-8.74, p = 0.03 for the CC genotype, and OR = 2.09, 95% CI = 1.24-3.53, p = 0.005 for the C allele). The genotype and allele frequencies of Glu298Asp and intron 4 were not significant between the patients with POAG and the controls, and after stratification by sex. The mean NOX plasma level was significantly lower in patients with POAG than in the controls (p = 0.01) and low in the (TC+CC) genotype compared to the TT genotype of T-786C in the patients and controls (p<0.001). CONCLUSIONS:The results suggest that the CC genotype of T-786C NOS3 may be associated with an increased risk of developing high-tension POAG in Egyptians, particularly women. In addition, decreased NO levels may play a role in the development of POAG.
Project description:Endothelial NOS (NOS3) has a potential role in the prevention of neuronal injury in hypoxic-ischemic encephalopathy (HIE). Thus, we aimed to explore the association between NOS3 gene polymorphisms and HIE susceptibility and symptoms in a Chinese Han population. Three single nucleotide polymorphisms (SNPs) in the NOS3 gene, rs1800783, rs1800779, and rs2070744, were detected in 226 children with HIE and 212 healthy children in a Chinese Han population. Apgar scores and magnetic resonance image scans were used to estimate the symptoms and brain damage. The association analyses were conducted by using SNPStats and SPSS 18.0 software. The genotype and allele distributions of rs1800779 and rs1799983 displayed no significant differences between the patients and the controls, while the rs2070744 allele distribution was significantly different (corrected P = 0.009). For clinical characteristics, the rs2070744 genotype distribution was significantly different in patients with different Apgar scores (≤5, TT/TC/CC = 6/7/5; 6~7, TT/TC/CC = 17/0/0; 8~9, TT/TC/CC = 6/2/0; 10, TT/TC/CC = 7/1/0; corrected P = 0.006) in the 1001 to 1449 g birth weight subgroup. The haplotype test did not show any associations with the risk and clinical characteristics of HIE. The results suggest that NOS3 gene SNP rs2070744 was significantly associated with HIE susceptibility and symptom expression in Chinese Han population.
Project description:Introduction:Multiple Sclerosis (MS) is a disease of central nervous system that mainly causes lesions or plaques in the spinal cord and brain. The purpose of this study was to analyze the relation between c.-813C>T (rs2070744) and c.894G>T (rs1799983) polymorphisms of NOS3 gene and MS in Iranian patients. Methods:A total of 78 patients with MS and 80 healthy controls were screened for NOS3 (rs2070744 and rs1799983) Single Nucleotide Polymorphisms (SNPs) by tetra-primer multiplex ARMS-PCR and PCR-RFLP. Results:Genotype frequencies of the c.-813C>T polymorphism in patients compared to controls were as follows: 53.8% to 80.0% for TT genotype, 41.0% to 18.8% for TC genotype, and 5.1% versus 1.2% for CC genotype (P=0.001). The frequencies of GG genotype was 57.7% and 78.8% and for GT genotype of c.894G>T polymorphism in patients compared to control subjects was 42.3% and 21.2%, respectively (P=0.004). Conclusion:Our results indicate that the studied NOS3 polymorphisms may be associated with MS in Iranian patients.
Project description:Background/aim:We aimed to investigate the associations between endothelial nitric oxide synthase(eNOS) gene polymorphisms [G894T (rs1799983)], intron 4 (27-bpTR) variable number tandem repeat (VNTR) and T786C (rs2070744), and ischemic stroke in the Anatolian population. Materials and methods:This case-control study included 112 patients with “stroke of undetermined etiology” and 160 controls. Real-time polymerase chain reaction (RT-PCR) analysis was used to analyze these polymorphisms. Between-group frequencies of alleles and genotypes were compared using binary logistic regression analysis. Results:No significant difference was observed between the two groups in terms of the genotype and allele distributions of the eNOS G894T (rs1799983) polymorphism (P > 0.05). The a alleles and the 4b/a and 4a/a genotypes of the intron 4 (27-bpTR) VNTR polymorphism had significantly higher frequencies in the patient group than in the control group (OR: 2.715, P < 0.001; OR: 3.396, P < 0.001; OR: 10.631, P = 0.016, respectively). On the contrary, the TC genotype and C alleles of the T786C (rs2070744) polymorphism had a significantly lower frequency in the patient group than in the control group (OR: 0.244, P < 0.001, OR: 0.605, P = 0.006, respectively) Conclusion:Our findings indicate that the eNOS G894T and T786C [rs2070744] polymorphisms are not associated with the risk of ischemic stroke, whereas the intron 4 [27-bpTR] VNTR may be a risk factor in the Anatolian population.