Support of the histaminergic hypothesis in tourette syndrome: Association of the histamine decarboxylase gene in a large sample of families

Iordanis Karagiannidis, Sandra Dehning, Paul Sandor, Zsanett Tarnok, Renata Rizzo, Tomasz Wolanczyk, Marcos Madruga-Garrido, Johannes Hebebrand, Markus M. Nöthen, Gerd Lehmkuhl, Luca Farkas, Peter Nagy, Urszula Szymanska, Zachos Anastasiou, Vasileios Stathias, Christos Androutsos, Vaia Tsironi, Anastasia Koumoula, Csaba Barta, Peter ZillPablo Mir, Norbert Müller, Cathy Barr, Peristera Paschou

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Abstract

Background: Gilles de la Tourette Syndrome is a neurodevelopmental disorder that is caused by the interaction of environment with a complex genetic background. The genetic etiology of the disorder remains, so far, elusive, although multiple promising leads have been recently reported. The recent implication of the histamine decarboxylase (HDC) gene, the key enzyme in histamine production, raises the intriguing hypothesis of a possible role of histaminergic dysfunction leading to TS onset. Methods: Following up on the finding of a nonsense mutation in a single family with TS, we investigated variation across the HDC gene for association with TS. As a result of a collaborative international effort, we studied a large sample of 520 nuclear families originating from seven European populations (Greek, Hungarian, Italian, Polish, German, Albanian, Spanish) as well as a sample collected in Canada. Results and Conclusions: Interrogating 12 tagging SNPs (tSNP) across the HDC region, we find strong over-transmission of alleles at two SNPs (rs854150 and rs1894236) in the complete sample, as well as a statistically significant associated haplotypes. Analysis of individual populations also reveals signals of association in the Canadian, German and Italian samples. Our results provide strong support for the histaminergic hypothesis in TS etiology and point to a possible role of histamine pathways in neuronal development.

Original languageEnglish
Pages (from-to)760-764
Number of pages5
JournalJournal of medical genetics
Volume50
Issue number11
DOIs
Publication statusPublished - Aug 8 2013

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Karagiannidis, I., Dehning, S., Sandor, P., Tarnok, Z., Rizzo, R., Wolanczyk, T., Madruga-Garrido, M., Hebebrand, J., Nöthen, M. M., Lehmkuhl, G., Farkas, L., Nagy, P., Szymanska, U., Anastasiou, Z., Stathias, V., Androutsos, C., Tsironi, V., Koumoula, A., Barta, C., ... Paschou, P. (2013). Support of the histaminergic hypothesis in tourette syndrome: Association of the histamine decarboxylase gene in a large sample of families. Journal of medical genetics, 50(11), 760-764. https://doi.org/10.1136/jmedgenet-2013-101637