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Endothelial nitric oxide synthase (NOS3) rs2070744 polymorphism and risk for multiple sclerosis

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

The possible role of oxidative stress and nitric oxide (NO) in the pathogenesis of multiple sclerosis (MS) has been suggested by several neuropathological, biochemical, and experimental data. Because the single-nucleotide polymorphism (SNP) rs2070744 in the endothelial nitric oxide synthase (eNOS or NOS3) gene (chromosome 7q36.1) showed association with the risk for MS in Iranians, we attempted to replicate the possible association between this SNP and the risk for MS in the Caucasian Spanish population. The frequencies of NOS3rs2070744 genotypes and allelic variants in 300 patients diagnosed with MS and 380 healthy controls were assessed with a TaqMan-based qPCR assay. The possible influence of the genotype frequency on age at onset of MS, the severity of MS, clinical evolutive subtypes of MS, and HLA-DRB1*1501 genotype were also analyzed. The frequencies of rs2070744 genotypes and allelic variants were not associated with the risk of developing MS and were not influenced by gender, age at onset and severity of MS, the clinical subtype of MS or the HLA-DRB1*1501 genotype. This study found a lack of association between NOS3 rs2070744 SNP and the risk for MS in Caucasian Spanish people.

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Acknowledgements

The quality of the English language was revised in detail by Professor James McCue. This work was supported in part by Grants RETICS RD16/0006/0004 (ARADyAL) (José A.G. Agúndez), PI15/00303 (Elena García-Martín) and PI18/00540 (Elena García-Martín) from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Madrid, Spain and GR18145 (José A.G. Agúndez) and IB16170 (José A.G. Agúndez) from Junta de Extremadura, Mérida, Spain. Partially funded with FEDER funds.

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Authors and Affiliations

  1. UNEx, ARADyAL Instituto de Salud Carlos III, University Institute of Molecular Pathology Biomarkers, Cáceres, Spain

    José A. G. Agúndez, Elena García-Martín & Christopher Rodríguez

  2. CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain

    Julián Benito-León

  3. Service of Neurology, Hospital Universitario Doce de Octubre, Madrid, Spain

    Julián Benito-León, María Díaz-Sánchez & Patricia Calleja

  4. Section of Neurology, Hospital La Mancha-Centro, Alcázar de San Juan, Ciudad Real, Spain

    Jorge Millán-Pascual & Laura Turpín-Fenoll

  5. Section of Neurology, Hospital Universitario del Sureste, C/ Marroquina 14, 3º B, Arganda del Rey, 28030, Madrid, Spain

    Hortensia Alonso-Navarro, José Francisco Plaza-Nieto & Félix Javier Jiménez-Jiménez

  6. Department of Medicine-Neurology, Hospital “Príncipe de Asturias”, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain

    Esteban García-Albea & Félix Javier Jiménez-Jiménez

Authors
  1. José A. G. Agúndez
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  2. Elena García-Martín
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  12. Félix Javier Jiménez-Jiménez
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Contributions

All authors fulfill the criteria of authorship and no one else who fulfills the criteria has been excluded. EG-M, JAGA, HA-N, and FJJ-J had the idea and designed the study. JAGA, EG-M, JB-L, JM-P, MD-S, PC, LT-F, HA-N, EG-A, JFP-N, and FJJ--J conducted clinical assessments and were involved in the samples collection. EG-M, JAGA, and CR performed genetic analyses. EG-M, JAGA, and FJJ-J were involved in the analysis and interpretation of data. EG-M and JAGA. obtained funding for the investigation EG-M, JAGA, HA-N, and FJJ-J drafted the manuscript. JAGA, EG-M, JB-L, JM-P, MD-S, PC, LT-F, HA-N, EG-A, JFP-N, and FJJ-J were involved in writing and critically revising the article, and all of them have approved the final submitted version.

Corresponding author

Correspondence to Félix Javier Jiménez-Jiménez.

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Conflict of interest

All authors declare that they have no conflicts of interest.

Ethical approval

This study was approved by the Ethics Committees of Clinical Investigation of the University Hospital "Príncipe de Asturias" (University of Alcalá, Alcalá de Henares, Madrid, Spain), the Infanta Cristina University Hospital (Badajoz, Spain), and was performed according to the Declaration of Helsinki of 1975.

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The participants in the study signed the informed consent after full explanation of the procedure.

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Agúndez, J.A.G., García-Martín, E., Rodríguez, C. et al. Endothelial nitric oxide synthase (NOS3) rs2070744 polymorphism and risk for multiple sclerosis. J Neural Transm 127, 1167–1175 (2020). https://doi.org/10.1007/s00702-020-02211-0

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  • DOI: https://doi.org/10.1007/s00702-020-02211-0

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