Abstract
Objectives. Cocaine is the second most used illegal drug in Europe. The transition from use to dependence involves both genetic and environmental factors. Genetic variation in neurotransmitter systems is involved in the susceptibility to cocaine dependence. We examined the possible contribution to cocaine dependence of 16 genes involved in the cellular machinery that controls neurotransmitter release: genes encoding proteins of the SNARE complex (STX1A, SNAP25, VAMP1 and VAMP2), fusion control elements (SYT1, SYT2, CPLX1, CPLX2, CPLX3 and CPLX4) and regulatory elements (STXBP1, SYP, SNPH, NSF, NAPA and RAB3A). Methods. We genotyped 121 SNPs, selected according to genetic coverage criteria, in 360 cocaine-dependent patients and 360 controls from Spain. Results. Single and multiple-marker analyses revealed a strong association between cocaine dependence and the NSF gene, encoding the N-ethylmaleimide-sensitive factor (P = 5.1e-04, OR = 2.44 (1.45–4.00) and P = 0.001, OR = 1.82 (1.28–2.59), respectively). The presence and absence of psychotic symptoms were also studied. Interestingly, when we considered the time between initial consumption and the onset of cocaine dependence, we observed that the association was mainly restricted to the group of patients that rapidly developed drug dependence (≤2 years; P = 2.98e-06, OR = 1.33 (1.20–1.47)). Conclusions. Our data show preliminary evidence that NSF may predispose not only to cocaine dependence, but also to an early onset of the dependence.
Acknowledgements
We are grateful to patients and controls for their participation in the study, and to M. Dolors Castellar and others from the “Banc de Sang i Teixits” (Hospital Vall d'Hebron, Barcelona) and to Rebeca Ortega, Nuria Voltes, Carolina López, Oriol Esteve and Esther García, for their collaboration in the recruitment of samples. This work was supported by the Instituto de Salud Carlos III-FIS (PI051982), the “Agència de Gestió d'Ajuts Universitaris i de Recerca-AGAUR” (2009GR00971) and the Department of Health of the Government of Catalonia (Generalitat de Catalunya). MR and NF-C are recipients of a “Miguel de Servet contract” from the Instituto de Salud Carlos III (Ministerio de Ciencia e Innovación) and a “Ajut Personal Investigador en Formació” from the Universitat de Barcelona, respectively. RC was supported by a fellowship of the Biomedical Network Research Centre on Rare Diseases (CIBERER). SNP genotyping services were provided by the Barcelona node of the Spanish National Genotyping Center (CEGEN; www.cegen.org).
Statement of Interest
None to declare.