PT  - JOURNAL ARTICLE
AU  - Iordanis Karagiannidis
AU  - Sandra Dehning
AU  - Paul Sandor
AU  - Zsanett Tarnok
AU  - Renata Rizzo
AU  - Tomasz Wolanczyk
AU  - Marcos Madruga-Garrido
AU  - Johannes Hebebrand
AU  - Markus M Nöthen
AU  - Gerd Lehmkuhl
AU  - Luca Farkas
AU  - Peter Nagy
AU  - Urszula Szymanska
AU  - Zachos Anastasiou
AU  - Vasileios Stathias
AU  - Christos Androutsos
AU  - Vaia Tsironi
AU  - Anastasia Koumoula
AU  - Csaba Barta
AU  - Peter Zill
AU  - Pablo Mir
AU  - Norbert Müller
AU  - Cathy Barr
AU  - Peristera Paschou
TI  - Support of the histaminergic hypothesis in Tourette Syndrome: association of the histamine decarboxylase gene in a large sample of families
AID  - 10.1136/jmedgenet-2013-101637
DP  - 2013 Nov 01
TA  - Journal of Medical Genetics
PG  - 760--764
VI  - 50
IP  - 11
4099  - http://jmg.bmj.com/content/50/11/760.short
4100  - http://jmg.bmj.com/content/50/11/760.full
SO  - J Med Genet2013 Nov 01; 50
AB  - 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.