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Serum vitamin D, vitamin D receptor and binding protein genes polymorphisms in restless legs syndrome

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A Correction to this article was published on 19 February 2021

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Abstract

Background/objectives

Several studies showed lower serum 25-hydroxyvitamin D levels in patients with idiopathic restless legs syndrome (RLS) compared with matched controls, and a single study showed an association between the rs731236 single nucleotide polymorphism (SNP) in the vitamin D receptor (VDR) gene and the risk for RLS. We aimed to study the relationship between the serum 25-hydroxyvitamin D levels and to confirm previous findings related to SNPs in the VDR and the GC vitamin D binding protein (GC) gene, with the risk for RLS in the Spanish Caucasian population.

Methods

We genotyped 285 idiopathic RLS patients and 325 age and sex-matched controls for VDRrs2228750, VDRrs7975232, VDRrs739837, VDRrs78783628, GCrs7041 and GCrs4588 SNPs using TaqMan assays, and determined serum 25-hydroxyvitamin D levels in 111 idiopathic RLS patients and 167 controls using an ELISA commercial kit.

Results

Serum 25-hydroxyvitamin D levels were significantly higher in RLS patients than in controls but were unrelated with the 7 SNPs studied. None of the 7 SNPs analyzed was associated with the risk for idiopathic RLS or with a positive family history of RLS. However, RLS patients carrying the rs7975232CC genotype or the rs7975232C allele, had a higher frequency of response to GABAergic drugs. Associations between the age at onset and the severity of RLS with SNPs were inconsistent.

Conclusions

This study shows an association between increased serum concentrations of 25-hydroxyvitamin D and a lack of association between 7 SNPs in the VDR and in the GC genes with RLS in the Spanish Caucasian population.

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Acknowledgements

This work was supported in part by Grants RETICS RD16/0006/0004 (ARADyAL), PI15/00303 and PI18/00540 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Madrid, Spain and GR18145 and IB16170 from Junta de Extremadura, Mérida, Spain. Partially funded with FEDER funds.

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Authors and Affiliations

  1. Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain

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

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

    Gemma Amo, José A. G. Agúndez & Elena García-Martín

  3. Fundació per la Recerça Biomèdica i Social Mútua de Terrassa, Terrassa, Barcelona, Spain

    Mónica Díez-Fairén, Ignacio Álvarez-Fernández & Pau Pastor

  4. Movement Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain

    Mónica Díez-Fairén, Ignacio Álvarez-Fernández & Pau Pastor

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

    Santiago Navarro-Muñoz, Laura Turpín-Fenoll, Jorge Millán-Pascual, Marta Recio-Bermejo & Rafael García-Ruiz

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

    Esteban García-Albea

Authors
  1. Félix Javier Jiménez-Jiménez
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  2. Gemma Amo
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  3. Hortensia Alonso-Navarro
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  4. Marisol Calleja
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  5. Mónica Díez-Fairén
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  7. Pau Pastor
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  8. José Francisco Plaza-Nieto
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  9. Santiago Navarro-Muñoz
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  10. Laura Turpín-Fenoll
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  15. José A. G. Agúndez
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  16. Elena García-Martín
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Contributions

FJJJ: Drafting/revising the manuscript for content, including medical writing for content; study concept or design; acquisition of data; analysis or interpretation of data; study supervision and coordination. GA: Drafting/revising the manuscript for content, including medical writing for content; acquisition of data. HAN: Drafting/revising the manuscript for content, including medical writing for content; study concept or design; acquisition of data; interpretation of data; study supervision and coordination. MC: Drafting/revising the manuscript for content, including medical writing for content; acquisition of data. MDF: Drafting/revising the manuscript for content, including medical writing for content; acquisition of data. IAF: Drafting/revising the manuscript for content, including medical writing for content; acquisition of data. PP: Drafting/revising the manuscript for content, including medical writing for content; study concept or design; acquisition of data; interpretation of data; study supervision and coordination. JFPN: Drafting/revising the manuscript for content, including medical writing for content; acquisition of data. SNM: Drafting/revising the manuscript for content, including medical writing for content; acquisition of data. LTF: Drafting/revising the manuscript for content, including medical writing for content; acquisition of data. JMP: Drafting/revising the manuscript for content, including medical writing for content; acquisition of data. MRB: Drafting/revising the manuscript for content, including medical writing for content; acquisition of data. RGR: Drafting/revising the manuscript for content, including medical writing for content; acquisition of data. EGA: Drafting/revising the manuscript for content, including medical writing for content; acquisition of data. JAGA: Drafting/revising the manuscript for content, including medical writing for content; study concept or design; acquisition of data; statistical analysis and interpretation of data; study supervision and coordination, obtaining funding. EGM: Drafting/revising the manuscript for content, including medical writing for content; study concept or design; acquisition of data; interpretation of data; study supervision and coordination, obtaining funding.

Corresponding author

Correspondence to Félix Javier Jiménez-Jiménez.

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All authors declare that they have no financial or non-financial conflict of interest.

Ethical approval

The study was approved by the corresponding Ethics Committees of the Hospitals involved. Specifically, the Ethics Committees of University Hospital “Príncipe de Asturias”, Universidad de Alcalá, Alcalá de Henares (Madrid, Spain); University Hospital “Infanta Cristina” (Badajoz, Spain); and Hospital La Mancha-Centro, Alcázar de San Juan (Ciudad Real, Spain).

Data accessibility statement

All data related to the current study, intended for reasonable use, is available from J.A.G. Agúndez (University Institute of Molecular Pathology Biomarkers, University of Extremadura -UNEx ARADyAL Instituto de Salud Carlos III, Av/de la Universidad S/N, E10071 Cáceres. Spain) and F.J. Jiménez-Jiménez (Section of Neurology, Hospital del Sureste, Arganda del Rey, Madrid, Spain).

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Written informed consent was obtained from all the participants before study enrollment.

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Jiménez-Jiménez, F.J., Amo, G., Alonso-Navarro, H. et al. Serum vitamin D, vitamin D receptor and binding protein genes polymorphisms in restless legs syndrome. J Neurol 268, 1461–1472 (2021). https://doi.org/10.1007/s00415-020-10312-9

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