Endothelial nitric oxide synthase (−786T&gt;C) polymorphism and migraine susceptibility

Han, Dongyi; Wang, Zhi Hao; Dong, Bin; Ya, HU; Zhao, Hui

doi:10.1097/md.0000000000012241

Cited by 15 publications

(10 citation statements)

References 31 publications

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“…One reason for conflicting and inconclusive results in genetic studies of NOS in headache could be variability due to population background. This was demonstrated previously by Dong et al in a meta-analysis reporting rs2070744 as a risk factor for migraine only in Caucasians [ 28 ]. Secondly, few studies analyzed identical SNPs, contributing to inconsistent results, specifically regarding haplotype analysis.…”

Section: Discussionsupporting

confidence: 71%

“…One of the identified SNPs, rs2297518, further correlates with increased risk of migraine in interaction with another variant in eNOS (rs743506) [ 25 ]. Results from eNOS studies were also conflicting [ 26 , 27 , 28 ]. In concordance with iNOS results, additional associations with migraine with aura were discovered with eNOS haplotype analysis [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of NOS Gene Polymorphisms in Relation to Cluster Headache and Predisposing Factors in Sweden

et al. 2020

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Cluster headache is characterized by activation of the autonomic-trigeminal reflex. Nitric oxide can trigger headaches in patients, and nitric oxide signaling is known to be affected in cluster headache. Based on the hypothesis of nitric oxide being involved in cluster headache pathophysiology we investigated nitric oxide synthases as potential candidate genes for cluster headache. We analyzed eight variants in the three forms of nitric oxide synthase (NOS) genes, inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS), and tested for association with cluster headache. Swedish cluster headache patients (n = 542) and controls (n = 581) were genotyped using TaqMan® assays on an Applied Biosystems 7500 qPCR cycler. This is the largest performed genetic study on NOS involvement in cluster headache so far. We found an association between cluster headache and one iNOS haplotype consisting of the minor alleles of rs2297518 and rs2779249 (p = 0.022). In addition, one of the analyzed nNOS variants, rs2682826, was associated with reported triptan use (p = 0.039). Our data suggest that genetic variants in NOS genes do not have a strong influence on cluster headache pathophysiology, but that certain combinations of genetic variants in NOS genes may influence the risk of developing the disorder or triptan use.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Analysis of NOS Gene Polymorphisms in Relation to Cluster Headache and Predisposing Factors in Sweden

et al. 2020

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“…NO is synthesized from L-arginine by three isozymes of nitric oxide synthase (NOS), containing neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) 75 . The role of NO in the pathogenesis of migraine has been proven in previous studies 24 . None of the previous trials have measured serum NO levels in the evaluation of the influence of ALA on migraine 60 – 62 .…”

Section: Discussionmentioning

confidence: 80%

The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines

Kelishadi

Naeini

Khorvash

et al. 2022

Sci Rep

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The current study was performed to evaluate the effects of alpha-lipoic acid (ALA) supplementation on lactate, nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) levels, and clinical symptoms in women with episodic migraines. Considering the inclusion and exclusion criteria, ninety-two women with episodic migraines participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The participants were randomly assigned to receive either 300 mg/day ALA or placebo, twice per day for 12 weeks. The primary outcomes included headache severity, headache frequency per month, and duration of attacks and the secondary outcomes included lactate (a marker of mitochondrial function), NO, and VCAM-1 serum levels were measured at baseline and the end of the intervention. At the end of the study, there was a significant decrease in lactate serum levels (− 6.45 ± 0.82 mg/dl vs − 2.27 ± 1.17 mg/dl; P = 0.039) and VCAM-1 (− 2.02 ± 0.30 ng/ml vs − 1.21 ± 0.36 ng/ml; P = 0.025) in the ALA as compared to the placebo group. In addition, the severity (P < 0.001), frequency (P = 0.001), headache impact test (HIT-6) (P < 0.001), headache dairy results (HDR) (P = 0.003), and migraine headache index score (MHIS) (P < 0.001) had significantly decreased in the intervention as compared to the control group. No significant changes were observed for NO levels and duration of migraine pains. ALA supplementation can be considered a potential adjunct treatment in patients with migraine due to its improving mitochondrial and endothelial functions and clinical symptoms.

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“…It has been described increased risk for stroke in a population-based study in the United States ( Fan et al, 2010 ), but this association was not replicated by a case-control association study in Turkey ( Anlıaçık et al, 2019 ). A meta-analysis showed an association between NOS3 rs2070744CC genotype and the risk for migraine in Caucasians ( Dong et al, 2018 ), but a replication study in the Caucasian Spanish population did not confirm this finding ( García-Martín et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Common Endothelial Nitric Oxide Synthase Single Nucleotide Polymorphisms are not Related With the Risk for Restless Legs Syndrome

Jiménez‐Jiménez

Agúndez²,

Gómez-Tabales³

et al. 2021

Front. Pharmacol.

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Because nitric oxide and endothelial dysfunction could play a role in the pathogenesis of idiopathic restless legs syndrome (RLS), as was suggested by some preliminary data, we investigated the possible association between the rs2070744 variants in the endothelial nitric oxide synthase (eNOS or NOS3) gene (chromosome 7q36.1) and the risk for RLS in a Caucasian Spanish population. We assessed the frequencies of NOS3 single nucleotide polymorphisms (SNPs) rs2070744, rs1799983, and rs79467411 genotypes and allelic variants in 273 patients with idiopathic RLS and 325 healthy controls using a TaqMan-based qPCR assay. We also analyzed the possible influence of genotype frequency on age at onset of RLS symptoms, gender, family history of RLS, and response to drugs commonly used in the treatment of RLS such as dopaminergic drugs, clonazepam, and GABAergic drugs. The frequencies of genotypes and allelic variants were not associated with the risk for RLS and were not influenced by gender, age, and positive family history of RLS. We identified weak statistical associations of the SNP rs1799983 with the response to dopamine agonists (Pc = 0.018 for the rs1799983 G/T genotype) and of the SNP rs79467411 with the response to clonazepam (Pc = 0.018 for the rs79467411 G allele), although these findings should be cautiously interpreted and require further confirmation. These associations aside, our findings suggest that common NOS3 SNPs are not associated with the risk for idiopathic RLS in Caucasian Spanish people.

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Endothelial nitric oxide synthase (−786T>C) polymorphism and migraine susceptibility

Cited by 15 publications

References 31 publications

Analysis of NOS Gene Polymorphisms in Relation to Cluster Headache and Predisposing Factors in Sweden

Analysis of NOS Gene Polymorphisms in Relation to Cluster Headache and Predisposing Factors in Sweden

The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines

Common Endothelial Nitric Oxide Synthase Single Nucleotide Polymorphisms are not Related With the Risk for Restless Legs Syndrome

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