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The Nonsynonymous Thr105Ile Polymorphism of the Histamine N-Methyltransferase is Associated to the Risk of Developing Essential Tremor

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Abstract

Objective We analyzed in patients with essential tremor (ET) the Thr105Ile polymorphism of the Histamine N-methyltransferase (HNMT) enzyme that is associated to Parkinson’s disease (PD) risk. Methods Leukocytary DNA from 204 ET patients and a control group of 295 unrelated healthy individuals was studied for the nonsynonymous HNMT Thr105Ile polymorphism by using amplification-restriction analyses. Results Patients with ET showed a higher frequency of homozygous HNMT 105Thr genotypes leading to high metabolic activity (p < 0.015) with a statistically significant gene-dose effect, as compared to healthy subjects. These findings were independent of gender, and of tremor localization, but the association of the HNMT polymorphism is more prominent among patients with late-onset ET (p < 0.007). Conclusion These results, combined with previous findings indicating alterations in the frequency for the HNMT Thr105Ile polymorphism in patients with PD, suggest that alterations of histamine homeostasis in the SNC are associated with the risk of movement disorders.

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Acknowledgments

We are thankful to Ms. Diana Herrero for technical assistance and to Prof. James McCue for assistance in language editing. This work was supported in part by Grants SAF 2003-00967 from Ministerio de Ciencia y Tecnología, FIS 05/1056, 06/1252 and RETICS 07/0064/0016 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III.

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Authors and Affiliations

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

    Maria C. Ledesma, Carmen Martínez & José A. G. Agúndez

  2. Department of Biochemistry and Molecular Biology, School of Biological Sciences, University of Extremadura, Avda. de Elvas s/n, 06071, Badajoz, Spain

    Elena García-Martín

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

    Hortensia Alonso-Navarro, Félix Javier Jiménez-Jiménez, Inmaculada Puertas & Lluisa Rubio

  4. Section of Neurology, Hospital de Móstoles, Móstoles (Madrid), Spain

    Julián Benito-León

  5. Service of Neurology, Hospital Universitario de Salamanca, Salamanca, Spain

    Tomás López-Alburquerque

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  1. Maria C. Ledesma
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Correspondence to Elena García-Martín.

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Ledesma, M.C., García-Martín, E., Alonso-Navarro, H. et al. The Nonsynonymous Thr105Ile Polymorphism of the Histamine N-Methyltransferase is Associated to the Risk of Developing Essential Tremor. Neuromol Med 10, 356–361 (2008). https://doi.org/10.1007/s12017-008-8040-3

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