1. ¹Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
2. ²Department of Genetics and Cytogenetics, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
3. ³INSERM, UMR_S679, Paris, France
4. ⁴Université Pierre et Marie Curie-Paris 6, UMR_S679, Pitié-Salpêtrière Hospital, Paris, France
5. ⁵Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany
6. ⁶Université Pierre et Marie Curie-Paris 6, EA 3974, Modelling in Clinical Research, Paris, France
7. ⁷The Danish Twin Registry, Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, Denmark
8. ⁸AP-HP, Pitié-Salpêtrière Hospital, Federation of Neurology, Paris, France

Correspondence: Professor Dr G Deuschl, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Schittenhelmstr. 10, Kiel 24105, Germany. Tel: +49 431 597 8500; Fax: +49 431 597 8502; E-mail: g.deuschl@neurologie.uni-kiel.de

⁹These authors contributed equally to this work.

¹⁰These authors contributed equally as senior authors to this work.

Received 24 June 2008; Revised 10 November 2008; Accepted 13 November 2008; Published online 17 December 2008.

Abstract

The genetic causes of essential tremor (ET) seem to be heterogeneous. Recently, ET has been found associated with a functional variant (Ser9Gly) of the dopamine D₃ receptor (DRD3), located in the ETM1 locus on chromosome 3q13.3 described for the first time in 1997. We examined this variant in three different populations from Germany, Denmark and France. We undertook an association study of the Ser9Gly variant in 202 cases with a familial history from unrelated families with ET, 97 cases with isolated non-familial ET and 528 healthy controls. In addition, linkage and segregation analyses were carried out in 22 ET families. The distribution of genotypes and allele frequencies showed no significant differences in the whole sample and in a subanalysis of familial and sporadic cases. Age at onset of tremor, tremor duration and tremor severity did not show an association with the genotype. In addition, the DRD3 variant was not found linked to the disease in a subset of informative ET families. We did not find a significant association of the DRD3 variant with ET nor linkage to the DRD3 receptor in German, Danish and French ET patients and families, suggesting that it is unlikely to be a causal factor for ET.