Close association between polymorphisms of the nitric oxide synthetase 3 gene and neurological disorders other than stroke.
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ABSTRACT:
SUBMITTER: Kapoor S
PROVIDER: S-EPMC3363344 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Close association between polymorphisms of the nitric oxide synthetase 3 gene and neurological disorders other than stroke.
International journal of general medicine 20120511
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Project description:ObjectiveThe aim of this study is to investigate the association between two polymorphisms of endothelial nitric oxide synthase (NOS3) and suicide attempts.MethodsWe genotyped 186 suicide attempters and 420 unrelated healthy controls. The following polymorphisms were analysed: T-786C and 27-bp repeat in intron 4.ResultsNo significant differences were found in genotype or in allelic distribution of the aforesaid polymorphisms. There were also no differences in the genotype distribution or allelic frequencies when separately assessing males and females or impulsive and non-impulsive attempters and normal controls. Estimated haplotype frequencies were similar in both groups.ConclusionOur data do not support the hypothesis that genetically determined changes in the NOS3 gene confer increased susceptibility for suicidal behavior.
| S-EPMC1914081 | biostudies-literature
Project description:Nitric oxide (NO) is a multifunctional signalling molecule and a neurotransmitter that plays an important role in physiological and pathophysiological processes. In physiological conditions, NO regulates cell survival, differentiation and proliferation of neurons. It also regulates synaptic activity, plasticity and vesicle trafficking. NO affects cellular signalling through protein S-nitrosylation, the NO-mediated posttranslational modification of cysteine thiols (SNO). SNO can affect protein activity, protein-protein interaction and protein localization. Numerous studies have shown that excessive NO and SNO can lead to nitrosative stress in the nervous system, contributing to neuropathology. In this review, we summarize the role of NO and SNO in the progression of neurodevelopmental, psychiatric and neurodegenerative disorders, with special attention to autism spectrum disorder (ASD). We provide mechanistic insights into the contribution of NO in diverse brain disorders. Finally, we suggest that pharmacological agents that can inhibit or augment the production of NO as well as new approaches to modulate the formation of SNO-proteins can serve as a promising approach for the treatment of diverse brain disorders.
| S-EPMC7256645 | biostudies-literature
Project description:Background/aimWe 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 methodsThis 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.ResultsNo 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)ConclusionOur 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.
| S-EPMC7018372 | biostudies-literature
Project description:Peroxisome proliferator-activated receptor-γ (PPARγ) plays a protective role against brain injury after stroke in mice. However, the relationship between PPARγ gene polymorphisms and the functional outcome of acute ischemic stroke (AIS) remains unknown. 8822 patients from The Third China National Stroke Registry (CNSR-III) after whole-genome sequencing, two functional single nucleotide polymorphisms(SNPs) in PPARγ, rs1801282 C > G and rs3856806 C > T, were further analysed. The primary outcome was neurological functional disability at three months. Of the 8822 patients, 968 (11.0%) and 3497 (39.6%) were carriers of rs1801282 and rs3856806, respectively. Carriers of rs3856806 showed reduced risks for three-month neurological functional disability (OR, 0.84; 95% CI, 0.73-0.98; p = 0.02) and reduced risks for higher infarct volume (OR 0.90, 95% CI, 0.81-0.99, p = 0.04). They also had a reduced risk of neurological functional disability only in case of lower baseline IL-6 levels (OR 0.64, 95% CI 0.48-0.84, Pinteraction = 0.01). Carriers of rs1801282 had a reduced risk for three-month neurological functional disability (OR 0.77, 95% CI, 0.61-0.99, p = 0.04). Our study suggested that PPARγ polymorphisms are associated with a reduced risk for neurological functional disability and higher infarct volume in AIS. Therefore, PPARγ can be a potential therapeutic target in AIS.
| S-EPMC11572223 | biostudies-literature
Project description:Background: Nitrous oxide (N2O), commonly known as laughing gas, is inhaled recreationally because it produces the feelings of euphoria and freedom from pain. The risk of neurological dysfunction secondary to N2O abuse and its clinical diagnosis are, however, not yet sufficiently recognized, especially in China. Here, we have summarized the key clinical characteristics of N2O-induced neurological disorders. Materials and Methods: We recruited 20 patients with N2O-induced neurological disorders and analyzed their clinical features, laboratory data, magnetic resonance imaging and electromyography. We also carried out a literature review and compared 99 previously reported patients with our case series to confirm our results. Subgroup analysis was performed to explore the difference in demographical and clinical characteristics of N2O abuse between Asian and non-Asian patients. Results: The most common initial symptoms of N2O-induced neurological disorders were weakness and/or paresthesia. Most patients presented with myelopathy and/or peripheral neuropathy. The most commonly involved segment of the spinal cord was the cervical spinal cord, extending over 4-6 vertebral levels, but more than half of the patients with myelopathy had no sensory change at the corresponding spinal level. Homocysteine was found to be the most sensitive and practical indicator for diagnosis. Subgroup analysis showed that the Asian patients (median: 22.0 years old, Q1-Q3:19.0-26.0 years old) with N2O abuse were younger than non-Asian patients [26.0 (22.3-31.0) years old, P = 2.8 × 10-4]. The incidence of myelopathy combined with peripheral neuropathy was significantly higher in Asian patients than in non-Asian patients, who had myelopathy or peripheral neuropathy (P = 2 × 10-5). Conclusions: Key clinical characteristics of N2O abuse are longitudinally extensive cervical myelopathy and peripheral neuropathy. Recognition of these traits in young people in the age group of 20-30 years will provide important guidance for accurate diagnosis of neurological disease associated with N2O abuse. The clinical manifestations differ in Asian patients and non-Asian patients.
| S-EPMC8110825 | biostudies-literature
Project description:This study aimed to investigate whether the -1026(A>C)(rs2779249) and +2087(A>G)(2297518) polymorphisms in the NOS2 gene were associated with chronic periodontitis (CP) and with salivary levels of nitrite (NO?-) and/or nitrate + nitrite (NOx). A group of 113 mixed-race patients were subjected to periodontal, genetic, and biochemical evaluations (65 CP/48 periodontally healthy subjects). DNA was extracted from oral epithelial cells and used for genotyping by polymerase chain reaction (real-time). Salivary NOx concentrations were determined using an ozone-based chemiluminescence assay. Association of CP with alleles and genotypes of the -1026(A>C) polymorphism was found (X² test, p = 0.0075; 0.0308), but this was not maintained after multiple logistic regression, performed to estimate the effect of covariates and polymorphisms in CP. This analysis demonstrated, after correction for multiple comparisons, that only the female gender was significantly associated with CP. Polymorphisms analyzed as haplotypes were not associated with CP. NOx levels were significantly higher in the control group of heterozygous individuals for both polymorphisms. In conclusion, the female gender was significantly associated with CP, and higher levels of salivary NOx were found in control subjects and associated with the heterozygous state of the NOS2 polymorphisms, reinforcing the potential of NO metabolites as markers of periodontitis status.
| S-EPMC5485952 | biostudies-literature
Project description:Impaired nitric oxide (NO) formation may be associated with endothelial dysfunction and increased cardiovascular disease risk in preeclampsia (PE). Functional single-nucleotide polymorphisms (SNPs) of nitric oxide synthase 3 (NOS3) (rs3918226) and guanylate cyclase 1, soluble, alpha 3 (GUCY1A3) (rs7692387) increase susceptibility to the adverse consequences due to inadequate generation of NO by the endothelium. However, no previous study has examined whether these SNPs affect NO formation in healthy pregnancy and in gestational hypertension (GH) and PE. Here, we compared the alleles and genotypes of NOS3 (rs3918226) and GUCY1A3 (rs7692387) SNPs in normotensive pregnant women (NP, n = 153), in GH (n = 96) and PE (n = 163), and examined whether these SNPs affect plasma nitrite concentrations (a marker of NO formation) in these groups. We further examined whether the interaction among SNP genotypes is associated with GH and PE. Genotypes were determined using TaqMan allele discrimination assays, and plasma nitrite concentrations were determined by an ozone-based chemiluminescence assay. Multifactor dimensionality reduction was used to examine the interactions among SNP genotypes. Regarding NOS3 rs3918226, the CT genotype (p = 0.046) and T allele (p = 0.020) were more frequent in NP than in GH, and GH patients carrying the CT+TT genotypes showed lower nitrite concentrations than NP carrying the CT+TT genotypes (p < 0.05). Regarding GUCY1A3 rs7692387, the GA genotype (p = 0.013) and A allele (p = 0.016) were more frequent in PE than in NP, and NP women carrying the GG genotype showed higher nitrite concentrations than GH or PE patients carrying the GG genotype (p < 0.05). However, we found no significant interactions among genotypes for these functional SNPs to be associated with GH or PE. Our novel findings suggest that NOS3 rs3918226 and GUCY1A3 rs7692387 may affect NO formation and association with hypertensive disorders of pregnancy.
| S-EPMC10925623 | biostudies-literature
Project description:ImportanceNeurological disorders have been linked to suicide, but the risk across a broad spectrum of neurological disorders remains to be assessed.ObjectivesTo examine whether people with neurological disorders die by suicide more often than other people and to assess for temporal associations.Design, setting, and participantsNationwide, retrospective cohort study on all persons 15 years or older living in Denmark, from 1980 through 2016 (N = 7 300 395).ExposuresMedical contact for head injury, stroke, epilepsy, polyneuropathy, diseases of myoneural junction, Parkinson disease, multiple sclerosis, central nervous system infections, meningitis, encephalitis, amyotrophic lateral sclerosis, Huntington disease, dementia, intellectual disability, and other brain diseases from 1977 through 2016 (n = 1 248 252).Main outcomes and measuresDeath by suicide during 1980-2016. Adjusted incidence rate ratio (IRRs) were estimated using Poisson regressions, adjusted for sociodemographics, comorbidity, psychiatric diagnoses, and self-harm.ResultsOf the more than 7.3 million individuals observed over 161 935 233 person-years (49.1% males), 35 483 died by suicide (median duration of follow-up, 23.6 years; interquartile range, 10.0-37.0 years; mean age, 51.9 years; SD, 17.9 years). Of those, 77.4% were males, and 14.7% (n = 5141) were diagnosed with a neurological disorder, equivalent to a suicide rate of 44.0 per 100 000 person-years compared with 20.1 per 100 000 person-years among individuals not diagnosed with a neurological disorder. People diagnosed with a neurological disorder had an adjusted IRR of 1.8 (95% CI, 1.7-1.8) compared with those not diagnosed. The excess adjusted IRRs were 4.9 (95% CI, 3.5-6.9) for amyotrophic lateral sclerosis, 4.9 (95% CI, 3.1-7.7) for Huntington disease, 2.2 (95% CI, 1.9-2.6) for multiple sclerosis, 1.7 (95% CI, 1.6-1.7) for head injury, 1.3 (95% CI, 1.2-1.3) for stroke, and 1.7 (95% CI, 1.6-1.8) for epilepsy. The association varied according to time since diagnosis with an adjusted IRR for 1 to 3 months of 3.1 (95% CI, 2.7-3.6) and for 10 or more years, 1.5 (95% CI, 1.4 to 1.6, P < .001). Compared with those who were not diagnosed with a neurological disorder, those with dementia had a lower overall adjusted IRR of 0.8 (95% CI, 0.7-0.9), which was elevated during the first month after diagnosis to 3.0 (95% CI, 1.9-4.6; P < .001). The absolute risk of suicide for people with Huntington disease was 1.6% (95% CI, 1.0%-2.5%).Conclusions and relevanceIn Denmark from 1980 through 2016, there was a significantly higher rate of suicide among those with a diagnosed neurological disorder than persons not diagnosed with a neurological disorder. However, the absolute risk difference was small.
| S-EPMC7042859 | biostudies-literature
Project description:AimTo investigate the association of polymorphisms in four critical genes implicated in the NO-forming pathway with ischemic stroke (IS) in a Chinese Han population.MethodsDNA samples of 558 IS patients and 557 healthy controls from Chinese Han population were genotyped using the Taqman(TM) 7900HT Sequence Detection System. Six SNPs (rs841, rs1049255, rs2297518, rs1799983, rs2020744, rs4673) of the 4 related genes (eNOS, iNOS, GCH1, and CYBA) in the NO forming pathway were analyzed using the SPSS 13.0 software package for Windows.ResultsOne SNP located in the intron of GCH1 (rs841) was associated with IS independent of the traditional cardiovascular risk factors in co-dominant and dominant models (P=0.003, q=0.027; P=0.00006, q=0.0108; respectively). Moreover, the combination of rs1049255 CC+CT and rs841 GA+AA genotypes was associated with significantly higher risk for IS after adjustments (OR=1.73, 95% CI: 1.27-2.35, P<0.0001, q<0.0001).ConclusionThe data suggest that genetic variants within the NO-forming pathway alter susceptibility to IS in Chinese Han population. Replication of the present results in other independent cohorts is warranted.
| S-EPMC4002730 | biostudies-literature
Project description:Affective disorders including major depressive disorder (MDD), bipolar disorder (BPD), and general anxiety affect more than 10% of population in the world. Notably, neuronal nitric oxide synthase (nNOS), a downstream signal molecule of N-methyl-D-aspartate receptors (NMDARs) activation, is abundant in many regions of the brain such as the prefrontal cortex (PFC), hippocampus, amygdala, dorsal raphe nucleus (DRN), locus coeruleus (LC), and hypothalamus, which are closely associated with the pathophysiology of affective disorders. Decreased levels of the neurotransmitters including 5-hydroxytryptamine or serotonin (5-HT), noradrenalin (NA), and dopamine (DA) as well as hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are common pathological changes of MDD, BPD, and anxiety. Increasing data suggests that nNOS in the hippocampus play a crucial role in the etiology of MDD whereas nNOS-related dysregulation of the nitrergic system in the LC is closely associated with the pathogenesis of BPD. Moreover, hippocampal nNOS is implicated in the role of serotonin receptor 1 A (5-HTR1 A) in modulating anxiety behaviors. Augment of nNOS and its carboxy-terminal PDZ ligand (CAPON) complex mediate stress-induced anxiety and disrupting the nNOS-CAPON interaction by small molecular drug generates anxiolytic effect. To date, however, the function of nNOS in affective disorders is not well reviewed. Here, we summarize works about nNOS and its signal mechanisms implicated in the pathophysiology of affective disorders. On the basis of this review, it is suggested that future research should more fully focus on the role of nNOS in the pathomechanism and treatment of affective disorders.
| S-EPMC6303682 | biostudies-literature