Association between the Stin2 VNTR polymorphism of the serotonin transporter gene and treatment outcome in alcohol-dependent patients.
OBJECTIVE
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, chi(2) (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% chi(2) (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.
Centro Asistencial "As Burgas", Curros Enríquez, 7, 1 degrees local-B, 32004 Ourense, Spain. Gerardo.florez.menendez@sergas.es
Gerardo
G
Florez
Pilar
P
Saiz
Paz
P
Garcia-Portilla
Sandra
S
Alvarez
Luis
L
Nogueíras
Blanca
B
Morales
Victoria
V
Alvarez
Eliecer
E
Coto
Julio
J
Bobes
D000437:Alcoholism / Q000235:genetics* / Q000534:rehabilitation; D016009:Chi-Square Distribution; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives / Q000627:therapeutic use; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011788:Quality of Life; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D000077236:Topiramate; D016896:Treatment Outcome
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D000077236:Topiramate; D005632:Fructose; D009271:Naltrexone