DRD2 Gene Polymorphisms Research Articles

Association of 5-HTTLPR, DRD4 gene polymorphisms with the accident tendentiousness of drivers

To investigate the relationship between 5-HTTLPR and/or DRD4 gene polymorphisms and the accident tendentiousness of drivers. A case-control study, including 42 patients and 46 controls, were performed using type-A behavior questionnaire and EPQ scale. 5-HTTLPR and DRD4 gene -521 C/T were detected by the PCR-RFLP technique. The scores of type-A behavior questionnaires, such as TH and TH + CH in exposure group were significantly higher than those in control group (P < 0.05). P and N scores of EPQ questionnaires in exposure group were significantly higher than those in control group, and L score in exposure group was significantly lower than that in control group (P < 0.05 or P < 0.01). There were significant differences in the frequencies of the genotypes and alleles of 5-HTTLPR gene between the cases and the controls (P < 0.05), but there were no significant differences in the frequencies of the genotypes and alleles of DRD4 gene between the two groups (P > 0.05). In the drivers with the accident tendentiousness, P scores in the cases with homozygous genotypes of the S/S in 5-HTTLPR gene were significantly higher than those in the cases with the genotypes of S/L and L/L in 5-HTTLPR gene (P > 0.05). E scores in subjects with homozygous genotypes of the T/T in DRD4 gene were significantly higher than those in subjects with genotypes of the T/C+C/C in DRD4 gene (P > 0.05). The driver accident tendentiousness may be associated with 5-HTTLPR gene, but not associated with DRD4 gene. The two genes are associated with the type-A behavior and personality characteristics of drivers with accident tendentiousness. However, 5-HTTLPR and DRD4 gene may not have synergism in these behaviors and personality.

Deficient dopamine D2 receptor function causes renal inflammation independently of high blood pressure.

Renal dopamine receptors participate in the regulation of blood pressure. Genetic factors, including polymorphisms of the dopamine D2 receptor gene (DRD2) are associated with essential hypertension, but the mechanisms of their contribution are incompletely understood. Mice lacking Drd2 (D2−/−) have elevated blood pressure, increased renal expression of inflammatory factors, and renal injury. We tested the hypothesis that decreased dopamine D2 receptor (D2R) function increases vulnerability to renal inflammation independently of blood pressure, is an immediate cause of renal injury, and contributes to the subsequent development of hypertension. In D2−/− mice, treatment with apocynin normalized blood pressure and decreased oxidative stress, but did not affect the expression of inflammatory factors. In mouse RPTCs Drd2 silencing increased the expression of TNFα and MCP-1, while treatment with a D2R agonist abolished the angiotensin II-induced increase in TNF-α and MCP-1. In uni-nephrectomized wild-type mice, selective Drd2 silencing by subcapsular infusion of Drd2 siRNA into the remaining kidney produced the same increase in renal cytokines/chemokines that occurs after Drd2 deletion, increased the expression of markers of renal injury, and increased blood pressure. Moreover, in mice with two intact kidneys, short-term Drd2 silencing in one kidney, leaving the other kidney undisturbed, induced inflammatory factors and markers of renal injury in the treated kidney without increasing blood pressure. Our results demonstrate that the impact of decreased D2R function on renal inflammation is a primary effect, not necessarily associated with enhanced oxidant activity, or blood pressure; renal damage is the cause, not the result, of hypertension. Deficient renal D2R function may be of clinical relevance since common polymorphisms of the human DRD2 gene result in decreased D2R expression and function.

Generational association studies of dopaminergic genes in reward deficiency syndrome (RDS) subjects: selecting appropriate phenotypes for reward dependence behaviors.

Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates.

S23 * NEUROBIOLOGICAL ENDOPHENOTYPES IN ALCOHOL DEPENDENCE * S23.1 * GENETIC DETERMINANTS OF ALCOHOL ADDICTION: SEARCHING FOR AN ENDOPHENOTYPE ASSOCIATED WITH SWEET LIKING IN POPULATION OF FAMILIES WITH HISTORY OF ALCOHOL ADDICTION

S23 * NEUROBIOLOGICAL ENDOPHENOTYPES IN ALCOHOL DEPENDENCE * S23.1 * GENETIC DETERMINANTS OF ALCOHOL ADDICTION: SEARCHING FOR AN ENDOPHENOTYPE ASSOCIATED WITH SWEET LIKING IN POPULATION OF FAMILIES WITH HISTORY OF ALCOHOL ADDICTION

Association of two DRD2 gene polymorphisms with acute and tardive antipsychotic-induced movement disorders in young Caucasian patients

Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamine system. This study aimed to replicate previously reported associations in candidate genes for acute and tardive antipsychotic-induced MD in a young Caucasian sample. In 402 patients (median age 26 years), a total of 13 polymorphisms were genotyped in eight dopamine-related candidate genes selected a priori from the literature (regarding dopamine and serotonin receptors, dopamine degradation, and free radicals scavenging enzymes pathways). Patients with MD used on average a higher haloperidol dose equivalent when compared to those without MD. The prevalence of MD was high and did not differ between first- and second-generation antipsychotics. Significant associations were found between (a) the TaqI_D polymorphism and akathisia (OR = 2.3, p = 0.001 for each extra C-allele) and (b) the -141C polymorphism and tardive dyskinesia (OR = 0.20, p = 0.001 for each extra Del allele). The other polymorphisms were not significantly associated with an MD. Two associations were found between genetic variation TaqI_D and the -141C polymorphisms in the DRD2 gene and antipsychotic-induced MD; one with acute akathisia and one with tardive dyskinesia. These were previously reported to be associated with tardive dyskinesia and acute parkinsonism, respectively. These results suggest that the contribution of these DRD2 gene variants in the vulnerability of antipsychotic-induced MD takes place in a more general or pleiotropic way.

Age at onset in bipolar disorder: Investigation of the role of TaqIA polymorphism of DRD2 gene in a Sardinian sample

Bipolar disorder (BD) is a highly heterogeneous and heritable psychiatric illness. Age at onset has been shown to be a powerful tool for dissecting both the phenotypic and genetic complexity of BD. In this article, we present findings from an association study between the DRD2 TaqIA polymorphism and age at onset, showing that both alleles and genotypes at this locus associate with early onset BD.

Association of DRD2 gene polymorphisms with mood disorders: A meta-analysis

In the past few decades, a number of studies have investigated the association of dopamine D2 receptor (DRD2) gene polymorphisms with mood disorders, but the findings are not always consistent. The aim of our study was to assess the association between DRD2 gene polymorphisms and mood disorders by using a meta-analysis. Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang, with the last report up to June 2010. Meta-analysis was performed in a fixed/random effect model by using the software Review Manager 4.2. We identified 19 separate studies using search, but only 14 separate studies (2157 cases and 3272 controls) were included in the current study. Meta-analysis was performed for three DRD2 gene polymorphisms (-141Cins/del, Ser311/Cys311, and TaqI A1). We performed meta-analysis in overall, Caucasian, and Asian populations. We also performed disease-specific meta-analysis in unipolar disorder and bipolar disorder. We found no association between DRD2 gene -141Cins/del polymorphism and mood disorders in overall and Caucasian populations (P>0.05). We also found no association between DRD2 gene Ser311/Cys311 polymorphism and mood disorders in overall, Caucasian, and Asian populations (P>0.05). An association of DRD2 gene TaqI A1 polymorphism with mood disorders was found in overall population, and the individuals with A1A1 genotype were more susceptible to mood disorders in comparison to those with A2A1 and A2A2 genotypes (OR=1.84, 95% CI=1.07-3.17, P=0.03). Meta-analysis is retrospective research that is subject to the methodological deficiencies of the included studies. This meta-analysis suggests that mood disorders may be associated with DRD2 gene TaqI A1 polymorphism, but not -141Cins/del and Ser311/Cys311.

Population-Based Case-Control Study of DRD2 Gene Polymorphisms and Alcoholism

ABSTRACT Several independent lines of evidence for genetic contributions to vulnerability to alcoholism exist. Dopamine is thought to play a major role in the mechanism of reward and reinforcement in response to alcohol. D2 dopamine receptor (DRD2) gene has been among the stronger candidate genes implicated in alcoholism. In this study, alcohol use was assessed in 196 randomly selected Kota individuals of Nilgiri Hills, South India. Six DRD2 SNPs were assessed in 81 individuals with alcoholism and 151 controls to evaluate the association between single nucleotide polymorphisms (SNPs) and alcoholism. Of the three models (dominant, recessive, and additive) tested for association between alcoholism and DRD2 SNPs, only the additive model shows association for three loci (rs1116313, TaqID, and rs2734835). Of six studied polymorphisms, five are in strong linkage disequilibrium forming onesingle haplotype block. Though the global haplotype analysis with these five SNPs was not significant, haplotype analysis using all six SNPs yielded a global P value of .033, even after adjusting for age. These findings support the importance of dopamine receptor gene polymorphisms in alcoholism. Further studies to replicate these findings in different populations are needed to confirm these results.

P.4.b.017 D2 dopamine receptor (DRD2) gene polymorphism and combat-related posttraumatic stress disorder in Vietnam veterans

In the past few decades, a number of studies have investigated the association of dopamine D2 receptor (DRD2) gene polymorphisms with mood disorders, but the findings are not always consistent. The aim of our study was to assess the association between DRD2 gene polymorphisms and mood disorders by using a meta-analysis.Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang, with the last report up to June 2010. Meta-analysis was performed in a fixed/random effect model by using the software Review Manager 4.2.We identified 19 separate studies using search, but only 14 separate studies (2157 cases and 3272 controls) were included in the current study. Meta-analysis was performed for three DRD2 gene polymorphisms (-141Cins/del, Ser311/Cys311, and TaqI A1). We performed meta-analysis in overall, Caucasian, and Asian populations. We also performed disease-specific meta-analysis in unipolar disorder and bipolar disorder. We found no association between DRD2 gene -141Cins/del polymorphism and mood disorders in overall and Caucasian populations (P > 0.05). We also found no association between DRD2 gene Ser311/Cys311 polymorphism and mood disorders in overall, Caucasian, and Asian populations (P > 0.05). An association of DRD2 gene TaqI A1 polymorphism with mood disorders was found in overall population, and the individuals with A1A1 genotype were more susceptible to mood disorders in comparison to those with A2A1 and A2A2 genotypes (OR = 1.84, 95% CI = 1.07–3.17, P = 0.03).Meta-analysis is retrospective research that is subject to the methodological deficiencies of the included studies.This meta-analysis suggests that mood disorders may be associated with DRD2 gene TaqI A1 polymorphism, but not -141Cins/del and Ser311/Cys311.

Effects of Genetic Variations in the Dopaminergic System on Fatigue in Humans: Gender Aspects

Changes in the functional status under the effect of intense mental exercise were studied in carriers of different variants of DAT1, DRD2, and COMT genes. The volunteers (n=140) performed 3-h monotonous mental work (information processing and logical problem solving). The degree of fatigue was evaluated before and after exercise by the HAM (Health status-Activity-Moods) and AMF (Acute Mental Fatigue) questionnaires. A significant relationship between the DAT1, DRD2, and COMT gene polymorphism and changes in the mental sphere status were revealed. The effects of these polymorphisms were the most pronounced in girls. The results are discussed within the framework of hypothesis on the effects of changes in the phasic/tonic dopamine proportion on the studied functions.

Influence of dopaminergic and serotoninergic genes on working memory in healthy subjects.

Working memory is an ability to keep information in short-term memory and manipulate them 'on line'. Working memory is also involved in complex frontal executive functions. The role of dopaminergic system in modulating working memory processes in prefrontal cortex is well established. Also the role of serotoninergic receptors is postulated. The purpose of this study was to assess the association between the polymorphisms of dopaminergic (DRD1, DRD3, DRD4, COMT) and serotoninergic (SERT--serotonin transporter, 5HT2A, 5HT2C) genes' polymorphisms and performance on WCST in 200 volunteers from the Polish population. We found the association between DRD1, DRD4, COMT and SERT genes polymorphisms and the performance on WCST. The results obtained in the study indicate that dopaminergic and serotoninergic genes may play a role in modulating the executive function and working memory processes in healthy subjects. The pattern of this influence may be different in males and females. Moreover, the relationship between the efficacy of prefrontal cognitive function and genes polymorphisms may differ between healthy subjects and schizophrenic patients.

Dopamine D2 receptor polymorphisms and susceptibility to alcohol dependence in Indian males: a preliminary study

BackgroundDopamine is an important neurotransmitter involved in reward mechanism in the brain and thereby influences development and relapse of alcohol dependence. The dopamine D2 receptor (DRD2) gene on chromosome 11 (q22-q23) has been found to be associated with increased alcohol consumption through mechanisms involving incentive salience attributions and craving in alcoholic patients. Therefore, we investigated the association of three single nucleotide polymorphisms (SNP) in DRD2 gene with alcohol dependence in the north Indian subjects.MethodsIn a retrospective analysis, genetic association of three polymorphisms from DRD2 gene with alcohol dependence was investigated using a case-control approach. Alcohol dependence was determined by DSM-IV criteria and a total of 90 alcoholics and 60 healthy unrelated age-matched control subjects were recruited. Odds ratio and confidence interval was calculated to determine risk conferred by a predisposing allele/genotype/haplotype. Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair-wise interactions between SNPs.ResultsThe study showed a significant association of -141C Ins allele and a trend of association of TaqI A1 allele of DRD2 with alcohol dependence. Haplotype with the predisposing -141C Ins and TaqI A1 alleles (-141C Ins-A-A1) seems to confer ≈ 2.5 times more risk to develop alcohol dependence.ConclusionsThe study provides preliminary insight into genetic risk to alcohol dependence in Indian males. Two polymorphisms namely, -141C Ins/Del and TaqI A in DRD2 gene may have clinical implications among Indian alcoholic subjects.

Novel Insights in Pharmacogenetics of Drug Response in Parkinson‘s Disease

receptor DRD2 gene, the dopamine transporter (DAT ) gene and μ1 opioid receptor (OPRM1) gene. Motor fluctuations have been associated with a DRD2 gene polymorphism [6], although other studies could not replicate this finding. Conflicting results have been reported concerning the relationship between the occurrence of drug-induced hallucinations in PD and genetic polymorphisms. While some studies demonstrated significant associations between hallucinations and polymorphisms in the DAT gene, the cholecystokinin (CCK ) gene and the apolipoprotein E (APOE) gene, others failed to replicate these results. Associations were found between sleep attacks without warning signs and a polymorphism in the DRD4 gene, the preprohypocretin (HCRT ) gene, the DRD2 gene and the catechol-O-methyl transferase (COMT ) gene. In addition, similar findings were found in recent studies investigating polymorphisms in genes encoding dopamine D 2 and D 3 receptors [7–9] and COMT [10]. Lin and colleagues investigated the role of angiotensin I-converting enzyme in levodopa response [11]. They demonstrated that patients with a homozygote (ins/ins) genotype of the ACE gene had a 2.5-times higher risk of levodopa-induced psychosis, a disabling complication, particularly in the later stage of the disease. The role of angiotensin I-converting enzyme in the development of levodopa-induced psychosis is relatively unexplored. It is necessary to reproduce this study in independent cohorts. We concluded that, in comparison with other subject areas such as psychiatry [12], relatively few efforts have been made to investigate the role of pharmacogenetics in the individual response to anti-PD drugs. The focus of pharmacogenetic studies in patients with PD was mainly on genes coding for drug receptors, drug transporters and synaptic drug-metabolizing enzymes (pharmacodynamics). The pharmacogenetic studies in both PD and psychiatry did not, for the most part, Parkinson’s disease (PD) is characterized by brady kinesia, rigidity and tremor, and is the result of degeneration of dopaminergic neurones in the substantia nigra pars compacta. PD has a prevalence of approximately 0.5–1% in persons of 65–69 years, rising to 1–3% among persons of 80 years and older [1]. Twin studies suggest a limited role for genetic factors in the etiology of PD, perhaps most prominently in early-onset forms [2]. The etiology of the common late-onset forms of PD remains largely to be elucidated. Anti-PD drugs, such as levodopa and the direct-acting dopamine agonists, are effective in reducing the motor symptoms of PD. However, these drugs are also associated with the development of motor complications, such as levodopainduced dyskinesia (LID), response fluctuations and side effects, such as hallucinations and excessive daytime sleepiness. In clinical practice, a large interindividual variability in drug response has been noticed. For example, up to 45% of levodopa users develop LID within 5 years, while others remain free of LID for many years [3]. Up to 25% of users of dopaminergic drugs develop hallucinations, whereas others do not [4].

Brief communication: Allelic and haplotypic structure at the DRD2 locus among five North Indian caste populations

The dopamine D2 receptor (DRD2) gene, with its known human-specific derived alleles that can facilitate haplotype reconstruction, presents an important locus for anthropological studies. The three sites (TaqIA, TaqIB, and TaqID) of the DRD2 gene are widely studied in various world populations. However, no work has been previously published on DRD2 gene polymorphisms among North Indian populations. Thus, the present study attempts to understand the genetic structure of North Indian upper caste populations using the allele and haplotype frequencies and distribution patterns of the three TaqI sites of the DRD2 gene. Two hundred forty-six blood samples were collected from five upper caste populations of Himachal Pradesh (Brahmin, Rajput and Jat) and Delhi (Aggarwal and Sindhi), and analysis was performed using standard protocols. All three sites were found to be polymorphic in all five of the studied populations. Uniform allele frequency distribution patterns, low heterozygosity values, the sharing of five common haplotypes, and the absence of two of the eight possible haplotypes observed in this study suggest a genetic proximity among the selected populations. The results also indicate a major genetic contribution from Eurasia to North Indian upper castes, apart from the common genetic unity of Indian populations. The study also demonstrates a greater genetic inflow among North Indian caste populations than is observed among South Indian caste and tribal populations.

Association between DRD4 gene polymorphism and personality variation in great tits: a test across four wild populations

Polymorphisms in the dopamine receptor D4 gene (DRD4) have been related to individual variation in novelty-seeking or exploratory behaviour in a variety of animals, including humans. Recently, the human DRD4 orthologue was sequenced in a wild bird, the great tit (Parus major) and a single nucleotide polymorphism in exon 3 of this gene (SNP830) was shown to be associated with variation in exploratory behaviour of lab-raised individuals originating from a single wild population. Here we test the generality of this finding in a large sample of free-living individuals from four European great tit populations, including the originally sampled population. We demonstrate that the association between SNP830 genotype and exploratory behaviour also exists in free-living birds from the original population. However, in the other three populations we found only limited evidence for an association: in two populations the association appeared absent; while in one there was a nonsignificant tendency. We could not confirm a previously demonstrated interaction with another DRD4 polymorphism, a 15 bp indel in the promoter region (ID15). As yet unknown differences in genetic or environmental background could explain why the same genetic polymorphism (SNP830) has a substantial effect on exploratory behaviour in one population, explaining 4.5-5.8% of the total variance-a large effect for a single gene influencing a complex behavioural trait-but not in three others. The confirmation of an association between SNP830 genotype and personality-related behaviour in a wild bird population warrants further research into potential fitness effects of the polymorphism, while also the population differences in the strength of the association deserve further investigation. Another important future challenge is the identification of additional loci influencing avian personality traits in the wild.

Associated Study between Dopamine DRD2 Gene Polymorphism and Finger Tapping Test

Associated Study between Dopamine DRD2 Gene Polymorphism and Finger Tapping Test

An association study of DRD2 gene polymorphisms with schizophrenia in a Chinese Han population

Dopamine signaling is strongly implicated in the etiology of schizophrenia (SZ). Because of the essential role dopamine D2 receptor (DRD2) in dopamine signaling, DRD2 gene has been regarded as one of the top candidate genes for SZ. However, the findings from linkage and association analyses on this gene are mixed and largely inconsistent across various studies. The aim of this study is to investigate the correlation of DRD2 gene variation and the risk for SZ in a Chinese Han population. Three SNPs (rs1801028, rs6275 and rs6277) of DRD2 gene were genotyped in a patient–control sample involving 421 SZ patients and 404 healthy controls. Our data indicated a nominally significant association of rs6277 with SZ, with T-allele being the risk allele (OR = 1.58, 95%CI = 1.03–2.43, P = 0.034). This study suggests that rs6277 T-allele may play a role in the genetic vulnerability for SZ, supporting the involvement of DRD2 gene in SZ pathogenesis.

P.1.a.005 DRD4 gene polymorphism association and response to methylphenidate in attention deficit hyperactivity disorder

P.1.a.005 DRD4 gene polymorphism association and response to methylphenidate in attention deficit hyperactivity disorder

Genetic and environmental influence on attachment disorganization

Empirical studies demonstrate that maternal sensitivity is associated with attachment security in infancy, while maternal frightening/frightened behavior is related to attachment disorganization. However, attachment disorganization is also predicted by individual dispositions in infancy. Indeed, recent studies indicate a link between attachment disorganization and DRD4 gene polymorphisms, thus suggesting a genetic vulnerability for attachment disorganization. The aims of our study were twofold, to test a) a possible direct link between molecular genetic variations and attachment disorganization, and b) a possible gene-environment interaction with a moderating effect of early maternal caregiving. Attachment security and disorganization, as well as quality of maternal behavior were assessed in the infants of the Regensburg Longitudinal Study IV (N = 106) at the age of 12 months. DNA samples were collected in order to assess the exon III repeat polymorphism in the coding region and the -521 C/T single nucleotide polymorphism (SNP) in the regulatory region of the DRD4 gene and a repeat polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene. Significant associations were found between attachment disorganization and the short polymorphism of the serotonin transporter gene. Also, a gene-environment interaction indicated that this genetic association was only valid for infants of mothers exhibiting low responsiveness. No other significant genetic associations with attachment disorganization were apparent. The study suggests a gene-environment interaction whereby biological determinants of attachment disorganization are moderated by social experiences. Different pathways of the development of attachment disorganization are discussed based on a bio-behavioral model of development.

Verbal but not performance IQ is highly correlated to externalizing behavior in boys with ADHD carrying both DRD4 and DAT1 risk genotypes

Objective Attention-deficit/hyperactivity disorder (ADHD) is often associated with reduced IQ and high levels of externalizing behavior (EB). This study tested if DRD4 7-repeat allele and DAT1 10-repeat allele homzygosity interact in modulating correlations between IQ and EB in affected boys. Methods Boys ( n = 130) between 6 and 12 years of age diagnosed with ADHD were included in the study. IQ and EB were assessed by WISC-III and Child Behavioral Checklist, respectively. The 40 bp variable number tandem repeat (VNTR) of the DAT1 gene and the 48 bp VNTR of the DRD4 gene polymorphisms were genotyped and 4 subgroups were defined by the presence/absence of the DRD4 7-repeat allele and by the presence/absence of the DAT1 10/10 genotype. Correlation coefficients were compared using the Fisher's Z transformation and regression lines by a Potthoff analysis. Results In the total sample, all correlation coefficients between EB score and IQ were non significant. Also, no differences in IQ were observed between the 4 genotype groups. However, different pattern of correlations between IQ and EB score appeared. In boys carrying no or only one genetic risk, IQ and EB score were uncorrelated while in children carrying both risk factors, negative and significant correlations emerged. Notably, correlation of EB to verbal IQ was strong ( r = − 0.71) and highly significant ( P < 0.01) in boys carrying both risk alleles. All pair-wise comparisons of correlation coefficients were significant for EB–verbal IQ correlation. Test of coincidence of regression lines did not show significant differences. Conclusions A specific domain of IQ, namely the verbal quotient is highly correlated to the level of EB in boys with ADHD carrying both dopaminergic risk genotypes. Further investigations are required to replicate these results and determine specificity to ADHD.