Gilles de la Tourette Syndrome (GTS) is a chronic neuropsychiatric disorder characterized by motor and vocal tics. Epidemiological evidence supports the importance of genetic factors in disease susceptibility, whereas pharmacological and neuroimaging studies have suggested a defect in the dopamine system. The dopamine receptor D2 gene (DRD2) has been reported to be associated with GTS and related phenotypes. Here, we evaluate genetic association between DRD2 and GTS in a sample from a South American population isolate (Antioquia, Colombia). We genotyped nine single nucleotide polymorphisms (SNPs) across the DRD2 gene region in 69 GTS patients and their nuclear families and carried out both SNP and haplotype-based transmission distortion analysis. Evidence for association was found for three SNPs (rs6279, rs1079597 and rs4648318) and a five marker-haplotype comprising both rs6279 and rs1079597. Our findings replicate the association of DRD2 and GTS, and are consistent with the proposed connection between the dopamine system and this complex neuropsychiatric disease.
aResearch Department of Genetics, Evolution and Environment, University College London
bLaboratorio de Genética Molecular
cDepartamento de Pediatría, Grupo Pediaciencias, Universidad de Antioquia, Medellín, Colombia
Correspondence to Barbara Kremeyer, Dipl.-Biol, PhD, Department of Genetics, Evolution and Environment, University College London, Wolfson House, 4 Stephenson Way, London NW1 2HE, UK
Tel: +44 20 7679 5036; fax: +44 20 7679 5052;
Ibi Herzberg and Ana Victoria Valencia-Duarte contributed equally to this study
Received 24 July 2009 Revised 20 December 2009 Accepted 18 January 2010