1. ¹School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia
2. ²Centre for Medical Research, University of Western Australia, Perth, WA, Australia
3. ³Western Australian Institute for Medical Research, Nedlands, WA, Australia
4. ⁴Department of Psychiatry, University of Bonn, Bonn, Germany
5. ⁵Methadon Maintenance Clinic 'Café-Ersatz', Bonn, Germany
6. ⁶Department of Psychiatry, University of Pecs, Pecs, Hungary
7. ⁷Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany
8. ⁸Centre for Clinical Research in Neuropsychiatry, University of Western Australia, Mt. Claremont, WA, Australia

Correspondence: Dr SG Schwab, Western Australian Institute for Medical Research, Sir Charles Gairdner Hospital, B-Block, Ground Floor, Hospital Ave., Nedlands, 6009 WA, Australia. Tel: +61 8 9346 2711; Fax: +61 8 9346 1818; E-mail: sschwab@cyllene.uwa.edu.au

⁹These two authors contributed equally.

Received 19 January 2005; Revised 4 April 2005; Accepted 22 May 2005; Published online 29 June 2005.

Abstract

The brain synaptic vesicular amine transporter SLCA18A2 is a key component for the uptake of monoamines like dopamine or serotonin into vesicles. We have analyzed seven DNA polymorphisms located in the genomic region of SLC18A2 for association with alcohol- and nicotine dependence, using a family-based design. Our sample comprised 131 families with alcohol-dependent offspring and 96 families with at least one nicotine-dependent offspring. For the alcohol-dependent sample, we found statistical significant association for two single markers (rs363387, P=0.03; rs363333, P=0.0066) as well as for several haplotypes (minimal P=0.0038). When the sample with alcohol dependence was stratified according to gender, we observed increased association for the male subgroup (rs363387, P=0.0011). None of the markers showed association in the sample of families with nicotine dependence. However, analysis of a combined sample of alcohol and nicotine-dependent families resulted in single markers as well as several haplotypes showing statistical significant association with substance dependence (minimal P=0.0044). We conclude that DNA polymorphisms located in SLC18A2 might contribute to the development of substance dependence.