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Changes at the CYP2C locus and disruption of CYP2C8/9 linkage disequilibrium in patients with essential tremor

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Abstract

To identify low-penetrance genes related to sporadic essential tremor (ET) at the CYP2Clocus, located in chromosome 10 q23.33. Leukocytary DNA from 200 ET patients and a control group of 300 unrelated healthy individuals with known CYP2C19 genotypes was studied for common CYP2C8 and CYP2C9 allelic variants by using amplification-restriction analyses. Patients with ET showed the following differences compared with healthy subjects: a 1.6-fold reduction in the frequency for CYP2C8*3 (p=0.006), a 1.35-fold reduction of CYP2C9*2 (p=0.05) and a 1.52-fold reduction in the frequency for CYP2C9*3 (p=0.07). The frequency for patients with ET carrying at least one defective allele was 1.33-fold reduced as compared with healthy subjects (p=0.002). In addition, a disruption of the CYP2C8*3/CYP2C9*2 linkage disequilibrium was observed in ET patients, with a 2.1-fold reduction in the percentage for carriers of the haplotype CYP2C8*3 plus CYP2C9*2 in ET patients (p=0.0001). These findings were independent of gender, age, age of onset, or clinical symptoms. These results suggest that alterations at the CYP2C gene locus are associated with the risk for ET.

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Authors and Affiliations

  1. Department of Pharmacology and Psychiatry, Medical School, University of Extremadura, Badajoz

    Carmen Martínez & José A. G. Agúndez

  2. Department of Biochemistry and Molecular Biology, School of Biological Sciences, University of Extremadura, Spain

    Elena García-Martín

  3. Department of Medicine-Neurology, Príncipe de Asturias Hospital, University of Alcalá, Alcalá de Henares (Madrid)

    Hortensia Alonso-Navarro, Félix Javier Jiménez-Jiménez, Isabel García-Ferrer, Pilar Vázquez-Torres & Inmaculada Puertas

  4. Móstoles Hospital, Móstoles (Madrid)

    Julián Benito-León & José M. Zurdo

  5. University Hospital of Salamanca, Salamanca, Spain

    Tomás López-Alburquerque

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  1. Carmen Martínez
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  2. Elena García-Martín
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  11. José A. G. Agúndez
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Correspondence to José A. G. Agúndez.

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Martínez, C., García-Martín, E., Alonso-Navarro, H. et al. Changes at the CYP2C locus and disruption of CYP2C8/9 linkage disequilibrium in patients with essential tremor. Neuromol Med 9, 195–204 (2007). https://doi.org/10.1007/BF02685892

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  • DOI: https://doi.org/10.1007/BF02685892

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