Dopamine D4 Receptor Gene Exon Research Articles

Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population.

Dopaminergic gene variants may affect nicotine dependence through their possible impact on the dopamine reward pathway. The purpose of this study is to investigate the relationship between the variable number tandem repeat (VNTR) variant in exon III of the Dopamine D4 receptor (DRD4) gene and genetic predisposition of smoking status in a Turkish population. We performed a study comparing 154 subjects as the smoker group, and 111 subjects as the non-smoker group. Genotyping for the DRD4 VNTR variant was performed using a PCR method. There was a significant difference between smoker and non-smoker groups regarding the distribution of the alleles and genotypes of the DRD4 gene (p=0.000, p=0.000, respectively). The 2R allele was higher in the non-smoker group compare to the smoker group (p=0.000). We found that the 2/7 and 4/9 genotypes were more common in smokers than non-smoker group (p=0.037, p=0.028, respectively) while 2/4 genotype was more prevalent in non-smokers than smokers (p=0.000). When the number of repeat alleles (48 bp) are accepted as short (S) if six or less, and as long (L) if seven or more, it was found that the frequency of S/S genotype of the DRD4 VNTR variant was lower in the smoker group and S/L genotype was higher in the smoker group (p=0.006, p=0.006, respectively). The subjects carrying the S/L genotype have a 2.25-fold increased risk for smoking than a non-smoker. The results indicated that the subjects carrying DRD4 exon III VNTR S/L genotype have a risk for smoking status in a Turkish population.

Association between the dopamine D4 receptor gene exon III variable number of tandem repeats and political attitudes in female Han Chinese.

Twin and family studies suggest that political attitudes are partially determined by an individual's genotype. The dopamine D4 receptor gene (DRD4) exon III repeat region that has been extensively studied in connection with human behaviour, is a plausible candidate to contribute to individual differences in political attitudes. A first United States study provisionally identified this gene with political attitude along a liberal-conservative axis albeit contingent upon number of friends. In a large sample of 1771 Han Chinese university students in Singapore, we observed a significant main effect of association between the DRD4 exon III variable number of tandem repeats and political attitude. Subjects with two copies of the 4-repeat allele (4R/4R) were significantly more conservative. Our results provided evidence for a role of the DRD4 gene variants in contributing to individual differences in political attitude particularly in females and more generally suggested that associations between individual genes, and neurochemical pathways, contributing to traits relevant to the social sciences can be provisionally identified.

Restoration of Glutamatergic Transmission by Dopamine D4 Receptors in Stressed Animals

The prefrontal cortex (PFC), a key brain region for cognitive and emotional processes, is highly regulated by dopaminergic inputs. The dopamine D4 receptor, which is enriched in PFC, has been implicated in mental disorders, such as attention deficit-hyperactivity disorder and schizophrenia. Recently we have found homeostatic regulation of AMPA receptor-mediated synaptic transmission in PFC pyramidal neurons by the D4 receptor, providing a potential mechanism for D4 in stabilizing cortical excitability. Because stress is tightly linked to adaptive and maladaptive changes associated with mental health and disorders, we examined the synaptic actions of D4 in stressed rats. We found that neural excitability was elevated by acute stress and dampened by repeated stress. D4 activation produced a potent reduction of excitatory transmission in acutely stressed animals and a marked increase of excitatory transmission in repeatedly stressed animals. These effects of D4 targeted GluA2-lacking AMPA receptors and relied on the bi-directional regulation of calcium/calmodulin kinase II activity. The restoration of PFC glutamatergic transmission in stress conditions may enable D4 receptors to serve as a synaptic stabilizer in normal and pathological conditions.

Dopamine D4 receptor gene exon III polymorphism associated with binge drinking attitudinal phenotype

Although binge drinking is a serious public health problem, relatively few studies have investigated the relationship between specific dopaminergic genes such as the dopamine D4 receptor ( DRD4) and binge drinking attitudinal phenotypes. This study used the DNA subsample ( N = 233, mean age 19.8, standard deviation, 0.89) of the National Longitudinal Study of Adolescent Health to investigate the association between a 48 base-pair variable number of tandem repeats in the DRD4 gene and a measure of binge drinking. Multivariate regression models indicated that the 7-repeat (7R) allele of the exon III polymorphism is significantly positively associated ( β = 0.16, P < .05) with binge drinking while controlling for low self-control and demographic variables. Findings were sturdy across race and gender. The present study provides unique evidence to the genetic underpinnings of binge drinking. Results suggest that the 7R allele may be an important contributor to the liability to binge drinking.

Novelty Seeking Involved in Mediating the Association Between the Dopamine D4 Receptor Gene Exon III Polymorphism and Heavy Drinking in Male Adolescents: Results from a High-Risk Community Sample

Previous research suggests that personality traits, particularly novelty seeking (NS), increase the risk of substance abuse. One possible explanation to account for this association relates to common genetic factors. The aim of this study was to examine whether allelic variants of the dopamine D4 receptor gene (DRD4) are associated with alcohol use in adolescents and to determine the extent to which these links are mediated by NS. Three hundred three adolescents (144 male participants, 159 female participants, approximately 15 years old) from a high-risk community sample completed self-report questionnaires measuring alcohol intake and temperament (Junior Temperament and Character Inventory [JTCI]). DNA was genotyped for the DRD4 exon III polymorphism. Male participants carrying the 7-repeat allele of DRD4 drank higher maximum amounts of alcohol per occasion and had greater lifetime rates of heavy drinking than male participants without this allele. Higher levels of NS were associated with higher alcohol intake in both genders. Multiple regression analyses support the role of NS in mediating the relationship between DRD4 and heavy drinking in male adolescents but not in female adolescents. These findings extend previous work highlighting the significance of personality traits as a mediating factor between genetic susceptibility and substance use during the period of early experimental use.

Novelty seeking: interaction between parental alcohol use and dopamine D4 receptor gene exon III polymorphism over 17 years

Recent meta-analyses have questioned the association between the dopamine receptor D4 (DRD4) gene polymorphism and the temperament trait of novelty seeking, and proposed an interaction between the polymorphism and other factors. We wanted to test whether parental alcohol use during childhood moderated the effect of an offspring dopamine receptor gene (DRD4) polymorphism on the temperament trait of novelty seeking in adulthood. A population-based sample of children and adolescents (n=2149) and their parents was examined in 1980 and 1983 on parental alcohol use and rearing practices. In 1997, study participants completed the Temperament and Character Inventory for the novelty-seeking temperament trait, and a subsample (n=150) was genotyped for the DRD4 exon III polymorphism. For the participants with the father, but not the mother, reporting more frequent alcohol consumption or drunkenness in examinations 17 and/or 14 years before the novelty-seeking assessment, an association between the short (two- or five-repeat) alleles of the DRD4 gene and extremely high novelty-seeking scores was observed. When the father reported less frequent alcohol consumption or drunkenness, the genotype was not associated with novelty seeking. The association remained after controlling for sex, age, and maternal child-rearing. These results provide preliminary information on gene-environment interaction on the temperament trait of novelty seeking and may partly explain the heterogeneity of findings concerning the association between DRD4 polymorphisms and novelty seeking.

The dopamine D4 receptor gene exon III polymorphism is associated with novelty seeking in 15-year-old males from a high-risk community sample

In recent years, studies focussing on a possible association between the dopamine D4 receptor (DRD4) gene exon III polymorphism and the personality trait of novelty seeking (NS) have yielded inconsistent results. The present study sought to examine the association of the DRD4-7r allele with NS in a sample of 303 15-year-old adolescents (144 males, 159 females) using data from a high-risk community sample. The Junior Temperament and Character Inventory--JTCI/12-18 was administered to assess dimensions of adolescent temperament. Males in the DRD4-7r allele group scored significantly higher on the NS (p=.002) and the harm avoidance (p=.045) scales than males without this allele. In females no association with temperament was observed. This association could not be explained by the presence of either an attention-deficit/hyperactivity disorder (ADHD) or a DRD4 by ADHD interaction.