Genetic variability related to serum uric acid concentration and risk of Parkinson's disease

Authors

  • Isabel González-Aramburu MD,

    1. Service of Neurology, Universitary Hospital Marqués de Valdecilla (IFIMAV), University of Cantabria (UC), Santander, Spain
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  • Pascual Sánchez-Juan MD,

    1. Service of Neurology, Universitary Hospital Marqués de Valdecilla (IFIMAV), University of Cantabria (UC), Santander, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
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  • Silvia Jesús MD,

    1. Movement Disorders Unit, Neurology and Clinical Neurophysiology Services, Instituto de Biomedicina de Sevilla (IBiS), Universitary Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
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  • Ana Gorostidi PhD,

    1. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    2. Biodonostia Research Institute, Donostia, Gipuzkoa, Spain
    3. Hospital Universitario Donostia, Department of Neurology, Donostia, Gipuzkoa, Spain
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  • Eduardo Fernández-Juan MD,

    1. Department of Biochemistry, Universitary Hospital Marqués de Valdecilla, Santander, Spain
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  • Fátima Carrillo MD,

    1. Movement Disorders Unit, Neurology and Clinical Neurophysiology Services, Instituto de Biomedicina de Sevilla (IBiS), Universitary Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
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  • María Sierra MD,

    1. Service of Neurology, Universitary Hospital Marqués de Valdecilla (IFIMAV), University of Cantabria (UC), Santander, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
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  • Pilar Gómez-Garre PhD,

    1. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    2. Movement Disorders Unit, Neurology and Clinical Neurophysiology Services, Instituto de Biomedicina de Sevilla (IBiS), Universitary Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
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  • María T. Cáceres-Redondo MD,

    1. Movement Disorders Unit, Neurology and Clinical Neurophysiology Services, Instituto de Biomedicina de Sevilla (IBiS), Universitary Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
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  • José Berciano MD,

    1. Service of Neurology, Universitary Hospital Marqués de Valdecilla (IFIMAV), University of Cantabria (UC), Santander, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
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  • Javier Ruiz-Martínez MD,

    1. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    2. Biodonostia Research Institute, Donostia, Gipuzkoa, Spain
    3. Hospital Universitario Donostia, Department of Neurology, Donostia, Gipuzkoa, Spain
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  • Onofre Combarros MD,

    1. Service of Neurology, Universitary Hospital Marqués de Valdecilla (IFIMAV), University of Cantabria (UC), Santander, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
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  • Pablo Mir MD, PhD,

    1. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    2. Movement Disorders Unit, Neurology and Clinical Neurophysiology Services, Instituto de Biomedicina de Sevilla (IBiS), Universitary Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
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  • Jon Infante MD

    Corresponding author
    1. Service of Neurology, Universitary Hospital Marqués de Valdecilla (IFIMAV), University of Cantabria (UC), Santander, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    • Correspondence to: Dr. Jon Infante Ceberio, Service of Neurology, Universitary Hospital Marqués de Valdecilla, Santander 39008, Spain; jinfante@humv.es

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  • Funding agencies: Marqués de Valdecilla Foundation-IFIMAV (CFR 05/11 to I.G.-A.); Instituto de Investigación Carlos III (FI12/00229 to I.G.-A.); Fondo de Investigación Sanitaria (Instituto de Investigación Carlos III) (PI11/00228 to J.I.); Ministerio de Economía y Competitividad de España (SAF2007–60700 to S.J., F.C., P.G.-G., P.M.); Instituto de Salud Carlos III (PI10/01674 and CP08/00174 to S.J., F.C., P.G.-G., P.M.); Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (CVI-02526 and CTS-7685 to S.J., F.C., P.G.-G., P.M.); Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0377/2007, PI-0741/2010, and PI-0437–2012 to S.J., F.C., P.G.-G., P.M.); Sociedad Andaluza de Neurología (to S.J., F.C., P.G.-G., P.M.); Jacques and Gloria Gossweiler Foundation (to S.J., F.C., P.G.-G., P.M.); Fundación Alicia Koplowitz (to S.J., F.C., P.G.-G., P.M.); “Miguel Servet” program from the Instituto de Salud Carlos III (to P.G.-G.); Marqués de Valdecilla Foundation-IFIMAV (WLA 04/11 to M.S.).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Background

Low serum uric acid (UA) levels have been associated with increased Parkinson's disease (PD) risk and accelerated disease progression. We analyzed the effect of polymorphisms in 9 genes influencing serum UA concentration on the risk of PD.

Methods

We genotyped SLC2A9 rs734553, ABCG2 rs2231142, SLC17A1 rs1183201, SLC22A11 rs17300741, SLC22A12 rs505802, GCKR rs780094, PDZK1 rs12129861, LRRC16A+SCGN rs742132, and SLC16A9 rs12356193 in 1061 PD patients and 754 controls. For each subject we calculated a cumulative genetic risk score (GRS), defined as the total number of PD-risk alleles (range, 2–15) associated to lower serum UA levels. Serum UA levels were measured in a subgroup of 365 PD cases and 132 controls.

Results

Serum UA levels were significantly lower in men with PD than in controls. Subjects (both men and women) carrying more than 9 risk alleles (third GRS tertile) had a 1.5 higher risk of developing PD than subjects with less than 8 risk alleles (first GRS tertile). An inverse correlation was observed between higher GRS and lower serum UA concentration in both men and women.

Conclusions

Genetic variability influencing serum UA levels might modify susceptibility to PD. © 2013 International Parkinson and Movement Disorder Society

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