The SLC6A3 gene possibly affects susceptibility to late-onset alcohol dependence but not specific personality traits in a Han Chinese population

Abstract

Dopaminergic dysfunction has an important role in the pathoetiology of alcohol dependence (AD). The purpose of this study was to determine whether the solute carrier family 6 member 3 (SLC6A3) gene (also known as the dopamine transporter DAT gene) was associated with AD, and whether variants in the SLC6A3 locus were associated with specific personality traits in patients with AD. Sixteen polymorphisms in SLC6A3 were analyzed using 637 patients with AD and 523 healthy controls. To reduce clinical heterogeneity, patients were classified into two subgroups: early-onset AD (EOAD) and late-onset AD (LOAD). The Tridimensional Personality Questionnaire was used to assess the personality traits novelty seeking (NS) and harm avoidance (HA) in the patients with AD. Using allele frequency and genotype distribution comparisons and logistic regression analysis, we found evidence of association between rs6350 and AD (P < 0.05). Following subgroup analysis, we confirmed evidence of an association in patients with LOAD (P = 0.003), but not in patients with EOAD. Heterozygous carriers of the A allele have a nearly 3 times greater risk to develop LOAD compared to individuals who do not have an A allele. Although we found that patients with AD had higher NS and HA scores compared to controls (P < 0.001), we did not find evidence of association between SLC6A3 polymorphisms and either NS or HA in patients with AD using linear regression analysis. The findings from our study indicate that the SLC6A3 gene may have a role in susceptibility to late-onset AD in the Han Chinese population.

NGF gene polymorphisms are not associated with heroin dependence in a Taiwanese male population

“…In fact, novelty seeking is the characteristics of sensation‐seeking personality in humans, and higher novelty seeking would predict the initiation of drug use, subsequent compulsive use, and the risk to relapse . Our finding is consistent with previous substance‐related studies, including alcohol, amphetamine, cocaine, tobacco, and cannabis . In addition, our study found a negative correlation between NS score and age in patients with HD, implying that adolescents display higher levels of novelty seeking than do adults, and may have higher risk for developing substance dependence …”

Association of FAAH p.Pro129Thr and COMT p.Ala72Ser with schizophrenia and comorbid substance use through next-generation sequencing: an exploratory analysis

“…It is well known that the SLC6A3 gene codes for the dopamine transporter; however, there is conflicting evidence regarding the transporter and its relation to substance dependence. [35][36][37][38][39] Some authors have proposed that these conflicting associations are due to the genetic position of the variants, since some are located in the first exons while others are in the 3'-UTR region, which affects either expression or proper transcription, hence the functional effect of the protein. 35 Our targeted sequencing approach was capable of detecting genetic variations across whole genes due to the fact that we included at least 50 bp of untranslated regions for sequencing.…”

“…[35][36][37][38][39] Some authors have proposed that these conflicting associations are due to the genetic position of the variants, since some are located in the first exons while others are in the 3'-UTR region, which affects either expression or proper transcription, hence the functional effect of the protein. 35 Our targeted sequencing approach was capable of detecting genetic variations across whole genes due to the fact that we included at least 50 bp of untranslated regions for sequencing. The association between substance use and intron 6 of SLC6A3 has been reported to have a regulatory impact, promoted by the union of transcriptional repressor CTCF.…”

Shared Behavioral and Neurocircuitry Disruptions in Drug Addiction, Obesity, and Binge Eating Disorder: Focus on Group I mGluRs in the Mesolimbic Dopamine Pathway

“…Polymorphisms in the variable number of tandem repeats (VNTR) in the 3′ untranslated region of the SLC6A3 gene coding for the DA transporter (DAT) have been reported in both obesity , and drug addiction. − DAT is important for maintaining dopaminergic tone via sequestering DA back into the presynaptic neuron. In vitro studies suggest that the SLC6A3 VNTR polymorphism influences gene expression and DAT availability.…”