In: Alcohol and alcoholism: the international journal of the Medical Council on Alcoholism (MCA) and the journal of the European Society for Biomedical Research on Alcoholism (ESBRA), Band 43, Heft 5, S. 516-522
<i>Objective:</i> To investigate the association between four polymorphisms of the 5-HT<sub>2A</sub> receptor and 5-HT transporter genes and heroin dependence. <i>Methods:</i> 113 heroin- dependent patients (DSM-IV criteria) and 420 unrelated healthy controls from Asturias (Northern Spain) were genotyped using standard methods. <i>Results:</i> There was an apparent difference in the distribution of genotypes for A-1438G polymorphisms (p = 0.024, not significant after Bonferroni correction). The 5-HT<sub>2A</sub> -1438A allele was significantly more common in patients than controls [0.55 and 0.45, respectively; corrected p = 0.042, OR = 1.51 (95% CI = 1.13–2.03)]. An interaction was observed between A-1438G of 5-HT<sub>2A</sub> and 5-HTT polymorphisms. The association between the -1438AA vs. AG/GG genotypes and heroin dependence was enhanced in the presence of 12-repeat 5-HTT VNTR and short 5-HTTLPR alleles [24.8% in heroin-dependent patients vs. 12.6% in controls; corrected p = 0.045, OR = 2.28 (95% CI = 1.36–3.82)]. <i>Conclusions:</i> Our findings support a contribution of the 5-HT<sub>2A</sub> gene to susceptibility to heroin dependence, as well as a possible synergistic effect of 5-HT<sub>2A</sub> and 5-HTT genes on susceptibility to heroin dependence.