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Non-synonymous polymorphism in the neuropeptide S precursor gene and sleep apnea

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Abstract

Background

Obstructive sleep apnea syndrome (OSAS) is a complex disease with a strong genetic basis. One of the primary molecular domains affected by OSAS is sympathetic activity. Neuropeptide S (NPS) plays an important role in the regulation of the sleep–wakefulness cycle, anxiety states, and daytime sleepiness. It is important to study neuropeptides related to sympathetic activity regulation and how their function could be modified by genetic variants affecting the expression of these molecules.

Objectives

We investigated the association of the non-synonymous polymorphism rs4751440 in the NPS precursor gene with OSAS and certain variables related to OSAS (daytime sleepiness, body mass index (BMI), insulin resistance, and blood pressure). This polymorphism causes an amino acid substitution in exon 3 of the human NPS precursor gene.

Patients and methods

We included 253 OSAS patients and 70 healthy subjects. Genotyping was done by polymerase chain reaction using specific flanking primers and agarose gel electrophoresis. Daytime sleepiness, BMI, plasma levels of high-density lipoprotein, glucose, total cholesterol, insulin, triglycerides, and the homeostasis model assessment index were also determined.

Results

A similar genotypic and allelic distribution was found in OSAS patients and controls. The risk of OSAS was not associated with the rs4751440 polymorphism. There was no significant interaction between daytime sleepiness or metabolic variables and the rs4751440 polymorphism.

Conclusion

Genotypic and allelic frequency distribution of the rs4751440 polymorphism was similar in OSAS patients and controls. In this population-based study, we could not show a significant association between rs4751440 polymorphism and susceptibility to OSAS or certain phenotypes related to OSAS (daytime sleepiness, BMI, systolic blood pressure, and insulin resistance) with the exception of diastolic blood pressure.

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Acknowledgements

The authors are grateful to the nursing staff of the sleep units of the different participating hospitals for their help during the course of the study.

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Authors and Affiliations

  1. Respiratory Diseases Research Unit, IRB Lleida, Lleida, Spain

    Manuel Sánchez-de-la-Torre, Zahid Hussain, Gerard Torres, Cristina Esquinas, Montserrat Martinez & Ferran Barbé

  2. Clinical Analysis Service, Hospital Universitari Son Dureta, Palma de Mallorca, Spain

    Javier Pierola, Antonia Barceló, Mónica de la Peña & Alvar G. N. Agustí

  3. Genetic Sequencing Unit, Hospital Universitari Son Dureta, Palma de Mallorca, Spain

    Carme Vidal

  4. Respiratory Service, Hospital Virgen del Rocio, Seville, Spain

    Francisco Capote

  5. Sleep Disorders Unit, Hospital Txagorritxu, University of the Basque Country, Vitoria, Álava, Spain

    Joaquín Durán

  6. Department of Psychiatry and Behavioral Sciences, Thorax Institute, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain

    Alvar G. N. Agustí & Luis de Lecea

  7. Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA

    Manuel Sánchez-de-la-Torre, Antonia Barceló, Mónica de la Peña, Joaquín Durán, Alvar G. N. Agustí, Luis de Lecea, Gerard Torres, Cristina Esquinas & Montserrat Martinez

  8. Respiratory Department, Hospital Universitario Arnau de Vilanova, Rovira Roure 80, 25198, Lleida, Spain

    Ferran Barbé

  9. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto Nacional de Salud Carlos III, Madrid, Spain

    Manuel Sánchez-de-la-Torre, Antonia Barceló, Mónica de la Peña, Joaquín Durán, Alvar G. N. Agustí, Gerard Torres, Cristina Esquinas, Montserrat Martinez & Ferran Barbé

Authors
  1. Manuel Sánchez-de-la-Torre
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  2. Javier Pierola
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  3. Carme Vidal
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  4. Antonia Barceló
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  5. Mónica de la Peña
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  6. Zahid Hussain
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  7. Francisco Capote
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  8. Joaquín Durán
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  9. Alvar G. N. Agustí
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  10. Luis de Lecea
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  11. Gerard Torres
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  12. Cristina Esquinas
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  13. Montserrat Martinez
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  14. Ferran Barbé
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Corresponding author

Correspondence to Ferran Barbé.

Additional information

Supported by: ABEMAR, SEPAR, and Fondo de Investigaciones Sanitarias (02/0334, 04/1593, 05/1059).

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Sánchez-de-la-Torre, M., Pierola, J., Vidal, C. et al. Non-synonymous polymorphism in the neuropeptide S precursor gene and sleep apnea. Sleep Breath 15, 403–408 (2011). https://doi.org/10.1007/s11325-010-0348-1

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  • DOI: https://doi.org/10.1007/s11325-010-0348-1

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