Association Between the Stin2 VNTR Polymorphism of the Serotonin Transporter Gene and Treatment Outcome in Alcohol-Dependent Patients

Abstract

Aims: The aim of this study was to investigate the potential association between functional polymorphisms of dopaminergic [dopamine receptor D2 (DRD2), dopamine receptor D3 (DRD3) and dopamine transporter (SLC6A3)] and serotonergic [serotonin 2A receptor (HTR2A) and serotonin transporter (SLC6A4)] genes and treatment outcome in alcohol-dependent patients. Methods: A total of 90 Spanish Caucasian alcohol-dependent outpatients (ICD-10 criteria) were enrolled in the study. The association between genotypes and drinking outcomes was measured over 6 months of treatment. Biomarkers of alcohol consumption, as well as alcohol consumption and its consequences, craving, disability and quality of life, were assessed. Based on those measures, we created a composite secondary measure to globally assess treatment outcome in alcoholism. Results: No association was found between DRD2, DRD3, SLC6A3 or HTR2A gene variants and treatment outcome. However, SLC6A4 STin2 12/12 carriers showed poor 6-month time point treatment outcome [32.8% in the good outcome group versus 64.0% in the poor outcome group, χ² (df) = 7.20 (1), corrected P = 0.042, OR (95% CI) = 0.27 (0.10–0.72)]. Nevertheless, independent analysis of each treatment group reveals that the excess of 12/12 carriers in the poor outcome group was only found in the naltrexone-treated group [24.1% versus 64.7% χ² (df) = 7.41 (1), corrected P = 0.042, OR (95% CI) = 0.17 (0.05–0.64)]. In the whole sample, the L-10 repeats haplotype (5-HTTLPR-STin2 VNTR) is associated with good outcome (LRT = 3.88, df = 1, P = 0.049). Conclusions: Our findings suggest that functional polymorphism of the SLC6A4 gene may have an influence on treatment outcome in alcohol-dependent patients.