The current study examines whether the dopamine transporter (DAT1) VNTR polymorphism and paternal alcoholism are related to serious alcohol problems. Using data from the National Longitudinal Study of Adolescent Health (Add Health), we found that the DAT1 polymorphism interacted with paternal alcoholism to predict serious alcohol problems among males. Specifically, the 10-repeat allele conferred an increase of alcohol problems only among males who also had an alcoholic father; the 10-repeat allele was unrelated to alcohol problems for males without an alcoholic father. Coefficient tests revealed that this interaction effect was stronger among African-American males. Females who possessed the 9-repeat allele were more likely to report serious alcohol problems, but this effect was not moderated by paternal alcoholism. These analyses suggest that additive and interactive effects of DAT1 and paternal alcoholism may operate differently across genders and races.
"Unlike the majority of DAT1 studies, the focus is on adolescents since early initiation and use strongly impacts long-term substance use problems as well as future educational and occupational opportunities (Hawkins et al., 1992; Kenkel, Ribar, Cook, & Peltzman, 1994; O'Donnell, Hawkins, Catalano, Abbott, & Day, 1995). Further, analyses are separated by gender as research generally suggests that different factors influence substance use decisions for males and females (Kendler & Prescott, 2006) and that the DAT1 gene's relationship with alcohol use may be contingent on gender (Vaske et al., 2009). "
[Show abstract][Hide abstract] ABSTRACT: Stressful life events can impact both substance use initiation and the quantity of substances consumed by adolescents; however, the effect of stress on substance use may be contingent on other factors including social support, peers, and genotype. DAT1, a polymorphic dopamine transporter gene, is one such factor that may be responsible for differential susceptibility to cumulative life pressures. Data from the National Longitudinal Study of Adolescent Health were utilized to determine whether adolescents with the 10-repeat allele are more likely to respond to life stresses by engaging in alcohol use than those without the allele. Respondents’ self-reports of key stressors were used to create a composite life stress scale. The interaction of this measure with the number of 10-repeat DAT1 alleles was evaluated in series of logistic regression models. A significant interaction emerged between stressful life experiences and DAT1 for
alcohol use among females, but this pattern was not seen in males. Females with the 10-repeat allele appear to be more sensitive to life stress as compared to those without the allele. It appears that variation in the DAT1 gene may help explain why some women are more likely to consume alcohol when confronted with stress. It, however, does not appear to condition the reaction of men, in terms of alcohol use, to stress.
"Differences in vulnerability to drug use may be linked to biological and trait-based differences that lead some to respond to stress by exhibiting selfdestructive behaviors (Sher et al., 2010; Aldridge-Gerry et al., 2011). Genetic vulnerability has been identified as one of these individual differences that make youth more vulnerable, and the effects of stressful life events on drug use can be conditioned by observable genetic differences between individuals (Ducci et al., 2008; Vaske et al., 2009). The diathesis-stress model suggests that individuals who experience stressful environments are more vulnerable to antisocial behaviors when they possess genetic risk factors and therefore are more at risk for engaging in substance use, violence, and having mental health problems in comparison to those who do not possess such risk. "
[Show abstract][Hide abstract] ABSTRACT: Purpose
Though stressful life events appear to impact the likelihood and frequency of substance use among adolescents, these effects are often varied and inconsistent. We suggest that the polymorphic MAOA gene may be partially responsible for variable susceptibility to environmental pressures and substance use. More specifically, we hypothesize that adolescents possessing low activity alleles for the MAOA genotype are more likely to respond to stressful life experiences by initiating substance use.
The genetic subsample of the National Longitudinal Study of Adolescent Health was analyzed (2,574 adolescents) using logistic regression models for each gender. Respondents’ self-reports of eight key stressors were used to create a composite life stress scale which was allowed to interact with a variable that represented the number of low activity MAOA alleles.
For males, a significant interaction emerged between stressful life experiences and the MAOA gene for alcohol (p = .029) and marijuana (p = .039) initiation. For females, the interaction was not significant in each model.
MAOA interacts with life stress to increase the likelihood of substance use initiation for males. Those with a low activity MAOA allele are more likely to initiate substance use than those with a high activity allele when exposed to stressful experiences.
"Very recently, a meta-analysis have suggested a possible association between the SLC6A3 VNTR 9* allele and alcoholic subgroup with alcohol withdrawal seizure or delirium tremens . Also, a gender-and paternal-effect was suggested . "
[Show abstract][Hide abstract] ABSTRACT: Dopamine is a neurotransmitter whose functions are mediated by five receptors expressed in several organs and tissues. Dopaminergic system dysfunctions are involved in the etiology or treatment of several pathological conditions, including drug addiction. Alcohol dependence (AD) is a widespread psychiatric disorder, affecting 5.4% of the general population lifetime. Family and twins studies support the role of a genetic component in AD. Since dopamine neurotransmission has been shown to be involved in drug reward, related genes are plausible candidates for susceptibility to AD. Here, we evaluated both the DRD2/ANKK1 TaqIA (rs1800497) and SLC6A3 40 bp-VNTR SNP and gene-gene interaction analysis in AD patients from a population of Central Italy. The study design was a case-control. In total, 280 alcoholic subjects (213 men and 67 woman) and 280 age- and sex-matched control subjects were recruited for this study. Case subjects met the DSM-IV criteria for AD and they are free from any psychiatric co-morbidities. Controls were subjects who had non-alcohol problem either never drank; those who have smoked at least one pack of cigarettes per day for at least 1 year were excluded. Genotyping was performed by allele-specific PCR and RFLP-PCR. SLC6A3 40 bp 3'UTR-VNTR displays no association with AD. DRD2/ANKK1 TaqIA genotype distribution is significantly associated to AD (O.R.=1.551, p=0.023), with A1* allele displaying an O.R.=1.403 (p=0.029). Gene-gene interaction analysis using three-way contingency table analysis by a log-linear model yielded no significant result. Our study in a population of Central Italy extends and confirms previous results and, for the first time, tested the gene-gene interaction between SLC6A3 and DRD2 in AD.
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