DRD2 Gene Polymorphisms Research Articles

An Information Theoretical Study of the Epistasis Between the CNR1 1359 G/A Polymorphism and the Taq1A and Taq1B DRD2 Polymorphisms: Assessing the Susceptibility to Cannabis Addiction in a Turkish Population.

Addiction is a complex, multi-factorial disease, and thus, analyzing genetic variants at multiple loci and gene-gene interactions among them (epistasis) can provide crucial clues about causative factors of addiction which cannot be detected with single-nucleotide polymorphism (SNP) association studies. In this study, we discuss the interaction between the 1359 G/A polymorphism of the CNR1 gene and the DRD2 gene polymorphisms and the net effect of any possible epistasis on the cannabis addiction phenotype in a Turkish population. Using bivariate synergy and mutual information concepts as a means of capturing the magnitude of interaction between marker pairs, the present study not only confirms the A1 marker allele as a risk factor but also reveals a finer-grained association between A and B markers which manifests itself both as a preventive and a risk factor. Our results indicate that the increased phenotype of cases require an individual to be either heterozygous at both loci or homozygous at locus B with homozygous risk factor A1A1 present. We hypothesize that overlapping expressions of CB1 and D2R is the cause of CB1-D2R interactions in cases of substance abuse and the different polymorphisms of CNR1 and DRD2 genes may have decisive roles in the nature of these interactions in terms of promoting or alleviating the cannabis addiction risk factor of the individual.

ANKK1/DRD2 locus variants are associated with rimonabant efficacy in aiding smoking cessation: pilot data.

Polymorphism of the DRD2 gene (rs1800497), previously termed Taq1A, includes the A1 and A2 alleles. The A1⁺ genotype (A1/A1, A1/A2) has been associated with smoking dependence. The present study determined which polymorphism of the DRD2 gene had a salutary outcome in administration of rimonabant, a drug used in smoking cessation and obesity studies. Seventy-six (76) smokers enrolled into a double-blind, placebo-versus-rimonabant, 10-week smoking cessation drug trial. Subjects provided a blood sample to determine whether they had the DRD2 A1⁺ genotype (A1/A1, A1/A2) or the DRD2 A1⁻ genotype (A2/A2). Smoking cessation (or continuation) was monitored on a weekly basis with on-site carbon monoxide (CO) monitoring. Smokers in the rimonabant A1⁻ group were significantly more successful in completely stopping smoking compared to subjects in the placebo A1⁻ group (P < 0.05). However, there was no difference in smoking cessation when the rimonabant A1⁺ group was compared to the placebo A1⁺ group. With respect to quantified verifiable/objective smoking cessation outcomes, exhaled CO (parts per million) was monitored during each week of the study. The rimonabant A1⁻ group compared to the placebo A1⁻ group was quantifiably smoking less at weeks 5, 6, and 7 (P < 0.05), at week 8 (P < 0.01), and at weeks 9 and 10 (P < 0.001). No significant difference was found in exhaled CO levels between rimonabant A1⁺ group and the placebo A1⁺ group in any of the weeks studied. These findings further support the rationale for incorporating genotyping into clinical trials, particularly smoking cessation trials. Rimonabant demonstrated early and sustained smoking cessation efficacy only in noncarriers of the A1 allele. These results also underscore the risks of heterogeneity contributing to type 2 errors, when analyzing (phase 2 or 3) data. The potential clinical, regulatory, and commercial benefits associated with expediting and enhancing drug development, vis-à-vis the integration of biomarkers in clinical research, is supported by our findings.

DRD4 and SLC6A3 gene polymorphisms are associated with food intake and nutritional status in children in early stages of development

Variants of dopamine system genes such as the DRD4 and the SLC6A3 genes may be involved in food intake regulation because the dopaminergic system influences food reward. We investigated an association of polymorphisms in the DRD4 (exon 3 VNTR) and SLC6A3 (3′UTR VNTR, rs2550948, rs2652511 and rs1048953) genes with food intake and nutritional status in children. This prospective cohort study recruited 359 children at birth. Dietary data and nutritional status were collected at 1 year, 3–4 years, and 7–8 years of age. The polymorphisms were analyzed using polymerase chain reaction based techniques. Food intake and nutritional status were compared among the different SNP genotypes. In the first year of life, DRD4.7R− children showed higher BMI Z-scores (P=.019) than the DRD4.7R+ cohort. At 3–4 years old, DRD4.7R− and SLC6A3.10R/10R children showed a higher intake of palatable foods (P=.024) and a higher waist circumference (P=.017). The rs1048953 SLC6A3 polymorphism was associated with average daily energy intake (P=.003) at 3–4 years and with a waist-to-height ratio of children at 7–8 years (P=.041). Carriers of high dopamine activity alleles of the VNTRs studied in DRD4 and SLC6A3 genes and carriers of T/T genotype of the variant rs1048953 SLC6A3 can present an increased risk for obesity related to overeating because high dopamine activity can increase the perceived incentive value of food reward.

Right secondary somatosensory cortex-a promising novel target for the treatment of drug-resistant neuropathic orofacial pain with repetitive transcranial magnetic stimulation.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex has analgesic effect; however, the efficacy of other cortical targets and the mode of action remain unclear. We examined the effects of rTMS in neuropathic orofacial pain, and compared 2 cortical targets against placebo. Furthermore, as dopaminergic mechanisms modulate pain responses, we assessed the influence of the functional DRD2 gene polymorphism (957C>T) and the catechol-O-methyltransferase (COMT) Val158Met polymorphism on the analgesic effect of rTMS. Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized, placebo-controlled, crossover study. Navigated high-frequency rTMS was given to the sensorimotor (S1/M1) and the right secondary somatosensory (S2) cortices. All subjects were genotyped for the DRD2 957C>T and COMT Val158Met polymorphisms. Pain, mood, and quality of life were monitored throughout the study. The numerical rating scale pain scores were significantly lower after the S2 stimulation than after the S1/M1 (P = 0.0071) or the sham (P = 0.0187) stimulations. The Brief Pain Inventory scores were also lower 3 to 5 days after the S2 stimulation than those at pretreatment baseline (P = 0.0127 for the intensity of pain and P = 0.0074 for the interference of pain) or after the S1/M1 (P = 0.001 and P = 0.0001) and sham (P = 0.0491 and P = 0.0359) stimulations. No correlations were found between the genetic polymorphisms and the analgesic effect in the present small clinical sample. The right S2 cortex is a promising new target for the treatment of neuropathic orofacial pain with high-frequency rTMS.

DRD4 gene polymorphism in great tits: gender-specific association with behavioural variation in the wild

Recent studies indicate that polymorphisms of the DRD4 gene may be related to behavioural variation in mammals and birds. The purpose of this study was to ascertain a connection between DRD4 genotypes and behavioural patterns in a wild passerine bird during breeding time. We evaluated changes in birds’ parental provisioning behaviour in the presence of a novel object. As a behavioural trait, we measured the duration of feeding interruption from the first time that each bird noticed the novel object until they entered the nest box. We found a gender-specific association between DRD4 gene polymorphism and parental behaviour. Males with a CC genotype delayed feeding for a longer period than those with CT and TT genotypes. No significant effect of genotype on provisioning behaviour was observed among females. We conclude that (i) DRD4 gene polymorphism in wild birds can be associated with behaviour related to fearfulness, and (ii) this effect is supposedly gender-specific during the breeding time, potentially explained by sex differences in parental care or hormonal levels.

Association between ANKK1 (rs1800497) polymorphism of DRD2 gene and attention deficit hyperactivity disorder: A meta-analysis

The role of dopamine neurotransmitter in attention deficit hyperactivity disorder (ADHD) remains controversial. Many molecular studies focusing on dopamine receptors have attempted to analyze the gene polymorphisms involved in dopaminergic transmission. Of these, rs1800497 (TaqIA) single nucleotide polymorphism (SNP) of the dopamine D2 receptor (DRD2) gene has been focused on by the most attention. However, this locus has recently been identified within the exon 8 of ankyrin repeat and kinase domain containing 1 (ANKK1), giving rise to a Glu713-to-Lys substitution in the putative ANKK1 protein. Thus, we performed a meta-analysis to determine whether ANKK1 polymorphism influences the risk of ADHD and examined the relationship between rs1800497 genetic variant and the etiology of ADHD. Relevant case-control studies were retrieved by database searches and selected according to established inclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Meta-regression, subgroup analysis, sensitivity analysis and cumulative meta-analysis were performed. A total of 11 studies with 1645 cases and 1641 controls were included. In the dominant model, the rs1800497 locus was associated with ADHD, with a pooled OR of 1.785 (95% CI=1.068–2.984, p=0.027). Subgroup analysis for ethnicity indicated that the polymorphism was associated with ADHD in Africans (OR=3.286, 95% CI=1.434–7.527, p=0.005), but not in East Asians (OR=1.513, 95% CI=0.817–2.805, p=0.188) and Caucasians (OR=1.740, 95% CI=0.928–3.263, p=0.084). However, the results of meta-regression indicated that publication date (p=0.601), source of controls (p=0.685), ethnicity (p=0.755) and diagnostic criteria (p=0.104) could not explain the potential sources of heterogeneity. This meta-analysis indicates that the rs1800497 locus may be associated with ADHD. These data provide possible references for future case-control studies in childhood disorders.

Association and family studies of DRD2 gene polymorphisms in alcohol dependence syndrome.

The human dopamine receptor 2 gene DRD2 plays a central role in susceptibility to Alcohol Dependence Syndrome (ADS). The aim of this study was to evaluate 3 single nucleotide polymorphisms: D2 (rs1076560), Tag1D (rs1800498), Tag1B (rs1079597) located in dopamine receptor 2 DRD2 gene and its role in alcohol dependence. DNA was provided from alcohol dependent (AD) patients (n=171) and healthy control subjects (n=160) all of Polish descent. The history of alcoholism was obtained using the Polish version of the SSAGA (Semi-Structured Assessment for the Genetics of Alcoholism). We conducted case-control association study and transmission disequilibrium test (TDT). Samples were genotyped using real-time PCR method. We did not confirm the association between studied polymorphisms and alcohol dependence syndrome. TDT reveled an adequate transmission of both alleles in the group of alcohol families. The lack of association of studied polymorphisms and ADS does not preclude its participation in the pathogenesis. Further research is needed to determine the actual contribution of DRD2 gene in the pathogenesis of alcoholism.

The relationship between DRD2 gene polymorphisms (C957T and C939T) and schizophrenia: A meta-analysis

Schizophrenia is a common, complex multi-factorial psychiatric disorder. Many studies have reported associations between the C957T and C939T polymorphisms in Dopamine D2 receptor (DRD2) gene and schizophrenia, but results are inconsistent. To derive a more precise estimation of the relationship, a meta-analysis was conducted to systematically summarize the possibility. We included 13 articles involving 3079 schizophrenia cases and 3851 healthy controls. Positive associations were found between C957T polymorphism and schizophrenia risk in C vs. T (OR=1.26, 95% CI=1.09–1.46, Praw=0.002, PFDR=0.005) and CC+CT vs. TT (OR=1.47, 95% CI=1.25–1.73, Praw<0.001, PFDR<0.001). When stratified by race, a significantly increased risk of schizophrenia was observed in Caucasians, but not in Asians. No association between C939T polymorphism and schizophrenia was found in overall or Asian population. Our study suggested that C957T of DRD2 gene polymorphism is likely to be a risk factor for schizophrenia, especially in Caucasian.

Stuttering candidate genes DRD2 but not SLC6A3 is associated with developmental dyslexia in Chinese population.

BackgroundDyslexia is a polygenic developmental disorder characterized by difficulties in reading and spelling despite normal intelligence, educational backgrounds and perception. Increasing evidences indicated that dyslexia may share similar genetic mechanisms with other speech and language disorders. We proposed that stuttering candidate genes, DRD2 and SLC6A3, might be associated with dyslexia.Methods and resultsThe study was conducted in an unrelated Chinese cohort with 502 dyslexic cases and 522 healthy controls. In total, 23 Tag SNPs covering the two genes were selected for genotyping through Tagger program. Association analysis was performed on each SNP alone and in haplotypes. One SNP markers in DRD2 showed significant association with developmental dyslexia.ConclusionThese findings indicate that polymorphism of DRD2 gene may be a risk factor of developmental dyslexia in the Chinese population.

The association between dopamine receptor (DRD4) gene polymorphisms and second language learning style and behavioral variability in undergraduate students in Turkey.

The dopamine D4 receptor gene (DRD4) encodes a receptor for dopamine, a chemical messenger used in the brain. One variant of the DRD4 gene, the 7R allele, is believed to be associated with attention deficit hyperactivity disorder (ADHD). The aim of this study was to investigate the relationships between repeat polymorphisms in dopamine DRD4 and second language learning styles such as visual (seeing), tactile (touching), auditory (hearing), kinesthetic (moving) and group/individual learning styles, as well as the relationships among DRD4 gene polymorphisms and ADHD in undergraduate students. A total of 227 students between the ages of 17-21 years were evaluated using the Wender Utah rating scale and DSM-IV diagnostic criteria for ADHD. Additionally, Reid's perceptual learning style questionnaire for second language learning style was applied. In addition, these students were evaluated for social distress factors using the list of Threatening Events (TLE); having had no TLE, having had just one TLE or having had two or more TLEs within the previous 6 months before the interview. For DRD4 gene polymorphisms, DNA was extracted from whole blood using the standard phenol/chloroform method and genotyped using polymerase chain reaction. Second language learners with the DRD4.7+ repeats showed kinaesthetic and auditory learning styles, while students with DRD4.7-repeats showed visual, tactile and group learning, and also preferred the more visual learning styles [Formula: see text]. We also demonstrated that the DRD4 polymorphism significantly affected the risk effect conferred by an increasing level of exposure to TLE.

The role of Dopamine 2 receptor gene and personality characteristics in alcohol dependence in Turkish population

Objective: Focusing on dopaminergic system, which is regarded to be responsible for alcohol dependence in many studies on animals and human beings, it is aimed to investigate TaqI A and B allel polymorphisms of Dopamine 2 receptor and personality characteristics in alcohol dependents and the relationship between these two parameters. Methods: In this study 64 alcohol dependent patients (3 females and 61 males) diagnosed according to DSM-IV diagnosis criteria, and 54 healthy subjects (8 female, 46 male) who themselves or whose first or second degree relatives had no alcohol dependence history were included. In order to determine their TaqI A and B alleles, blood samples were drawn from the participants, and then they were applied Temperament and Character Inventory and Michigan Alcoholism Screening Test scales. Results: Subjects with and without alcohol dependence revealed no significant difference as regards the frequency of TaqI A1 and B2 minor allel polymorphisms of DRD2 gene. It was also determined that the alcohol dependents had significantly higher scores in novelty seeking and harm avoidance dimensions, and lower scores in self-directedness and cooperativeness dimensions than the controls. In alcohol dependents, no association was determined between the personality characteristics and TaqI A1 and B2 minor allel polymorphisms. Conclusion: Not only one gene, but also several other minor genes in addition to personality characteristics and environment may play a role in vulnerability to alcohol dependence. In alcohol dependents, high novelty seeking is associated with the increase in impulsive behaviour, and may be important for the onset of alcohol taking behaviour. High level of harm avoidance may lead to taking alcohol continuously in order to deal with stress. Key words:

P.1.a.006 Single nucleotide polymorphisms and clozapine response in Korean schizophrenic patients who are refractory or intolerant to conventional antipsychotic agents

Schizophrenia is a common, complex multi-factorial psychiatric disorder. Many studies have reported associations between the C957T and C939T polymorphisms in Dopamine D2 receptor (DRD2) gene and schizophrenia, but results are inconsistent. To derive a more precise estimation of the relationship, a meta-analysis was conducted to systematically summarize the possibility. We included 13 articles involving 3079 schizophrenia cases and 3851 healthy controls. Positive associations were found between C957T polymorphism and schizophrenia risk in C vs. T (OR = 1.26, 95% CI = 1.09–1.46, Praw = 0.002, PFDR = 0.005) and CC + CT vs. TT (OR = 1.47, 95% CI = 1.25–1.73, Praw < 0.001, PFDR < 0.001). When stratified by race, a significantly increased risk of schizophrenia was observed in Caucasians, but not in Asians. No association between C939T polymorphism and schizophrenia was found in overall or Asian population. Our study suggested that C957T of DRD2 gene polymorphism is likely to be a risk factor for schizophrenia, especially in Caucasian.

The Correlation of Attention Deficit Hyperactivity Disorder with DRD4 Gene Polymorphism in Turkey

The Correlation of Attention Deficit Hyperactivity Disorder with DRD4 Gene Polymorphism in Turkey

Polymorphisms of the Dopamine D4 Receptor Gene in Stabled Horses are Related to Differences in Behavioral Response to Frustration.

Simple SummaryIn this study, the association between behavioral responses to frustration and DRD4 polymorphisms was investigated in horses. Twenty one horses were observed for 4–4.5 h during feeding for several days. Horses were then genotyped for the DRD4 gene. Behavioral responses to frustration were recorded more frequently in horses without the A allele than in horses with the A allele. These results indicate that polymorphisms of DRD4 should be considered when assessing the welfare of stabled horses, by means of behavioral indicators of frustration.In stabled horses, behavioral responses to frustration are often observed, especially around feeding time. These behavioral responses are a useful indicator of their welfare. In this study, we investigated the association between this behavioral indicator and DRD4 gene polymorphisms in stabled horses. Twenty one horses housed in two stables were used. The horses were observed for approximately 4 h around feeding over three or more days using focal-sampling and instantaneous-sampling. Horses were genotyped for the A–G substitution in the DRD4 gene. The effects of the A–G substitution (with or without the A allele in the DRD4 gene), the stables, and their interaction on the frequency of behavioral responses to frustration were analyzed using general linear models. The total time budget of behavioral responses to frustration was higher in horses without the A allele than in those with the A allele (P = 0.007). These results indicate that the A–G substitution of the DRD4 gene is related to frustration-related behavioral responses in stabled horses. Appropriate consideration should be made for the DRD4 gene polymorphism when the welfare of stabled horses is assessed, based on this behavioral indicator.

Dopamine receptor (D4) polymorphism is related to comorbidity between marijuana abuse and depression

The rates of marijuana abuse are steadily increasing in the U.S. Data suggest that comorbid marijuana abuse and depression is associated with worse outcomes than either diagnosis. Genetic studies independently link the DRD4 gene polymorphism to substance use and to internalizing disorders, but no study has examined whether the DRD4 polymorphism is linked to comorbid marijuana use and depression in a population sample. This study examined associations between the DRD4 gene 48bp VNTR polymorphism and comorbidity between marijuana use frequency and depression in a diverse, non-clinical adolescent sample (n=1882; ages 14 to 18) from the National Longitudinal Study of Adolescent Health (Add Health). Multinomial regression analyses indicated that the odds of being comorbid for depressive symptoms and marijuana use are approximately 2.5≥ with the ≥7R/≥7R genotype than youths who carry the <7R/<7R genotype, controlling for the effects of ethnicity, gender, age, violent victimization, and alcohol related problems. Findings provide genetic clues for psychopathology characterized by prominent externalizing and internalizing features.

Targeted D4 Dopamine Receptors: Implications for Drug Discovery and Therapeutic Development

A wealth of preclinical and clinical literature has established functional associations of CNS dopamine (DA) and its multiple G protein-coupled receptor (GPCR) types in the integration of key neurological processes linked to complex behavioral activities. Conversely, an equivalent vast literature supports the role of aberrant CNS DA expression and DA receptor signaling in the etiology and persistence of major psychiatric illnesses and has established selective targeting of DA-ergic systems as a cornerstone of pharmacotherapeutic intervention and current neuroleptic drug development. The present short review focuses on potential functional/behavioral alterations linked to polymorphisms in the primary DNA sequence of the DA receptor type 4 (DRD4) gene in reference to major psychiatric illnesses. The potential clinical relevance of major polymorphisms of the DRD4 gene are discussed within the context of practical aspects of typical and atypical neuroleptic drug usage within afflicted populations of psychiatric patients. It is anticipated that additional complementary molecular, biochemical, and behavioral studies of DRD4 gene polymorphisms will provide essential information for selective targeting of heterogeneous populations of CNS D4 receptors and advance drug discovery and therapeutic development efforts for highly efficacious treatment of psychiatric illnesses.

DRD2 and ANKK1 Gene Polymorphisms and Alcohol Dependence: A Case–Control Study among a Mendelian Population of East Asian Ancestry

Dopamine receptors are extensively studied in association with alcohol dependence (AD), since they are thought to be the key neural substrate for alcohol and other drug-related reinforcement and reward behaviours. The present study aims to understand the role of dopamine receptors in susceptibility to AD with respect to three sites of DRD2 gene (-141C Ins/Del, TaqIB and TaqID) and TaqIA site of ANKK1 gene among Meiteis of Manipur, a Mendelian population of India. A total of 129 individuals who all met the DSM-IV criteria for AD and 286 controls were screened for four single-nucleotide polymorphisms (SNPs) -141C Ins/Del, TaqIB TaqID and TaqIA. Both AD cases and controls were unrelated up to first cousin. Early age of onset of alcohol consumption and smoking status were significantly associated with AD. Improvement in education and occupation statuses showed decreased risk of AD. The heterozygous and mutant homozygous conditions of ANKK1 TaqIA polymorphism were found to be significantly associated with AD (odds ratio = 2.13, 95% confidential interval 1.04-4.39, P < 0.05), whereas a borderline significance of the -141C Del allele was observed (P = 0.059). Such a trend was not observed between AD and the other polymorphism, i.e., TaqIB and TaqID. Individuals carrying the A1 allele of ANKK1 TaqIA polymorphism may be relatively more susceptible to AD. Interaction of both ANKK1 TaqIA and -141C Ins/Del polymorphism is likely to increase risk of AD phenotypes among Meiteis of Manipur, India.

The ADH1B and DRD2 gene polymorphism may modify the protective effect of the ALDH2 gene against heroin dependence

Understanding the influences of genes involved in dopamine and serotonin metabolism, such as the aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) genes, is critical for understanding addictive behavior. In addition, dopamine D2 receptor (DRD2) gene may also interact with the dopamine metabolizing genes and link to addiction. Therefore, we investigated the association between the ALDH2, ADH1B and DRD2 polymorphisms and heroin dependence. Heroin-dependent Han Chinese patients (n=304) and healthy controls (n=335) were recruited. Genotypes of ALDH2, ADH1B and DRD2 polymorphisms were analyzed using a polymerase chain reaction with restriction fragment length polymorphism. The frequency of the ALDH2*1/*1 genotype was significantly lower in heroin-dependent patients than in controls, but the frequency of ADH1B and DRD2 genotypes was not significantly different. Further stratification of the ALDH2 gene with the ADH1B gene showed that the protective effect of ALDH2*1/*1 existed only in patients who also carried the ADH1B*1/*1 and ADH1B*1/*2 genotype. Logistic regression analysis showed a significant interaction between ALDH2 and ADH1B (P=0.022) and DRD2, ALDH2 and ADH1B in patients (P=0.037). The ALDH2*1/*1, ADH1B*1/*1, and ADH1B*1/*2 genotypes may interact and protect their carriers against heroin dependence and the protective effect may be varied by the DRD2 gene polymorphism. We conclude that the protective effect of the ALDH2 polymorphism against heroin dependence may be modified by the ADH1B and DRD2 polymorphism.

P.3.c.044 Influence of ANKK1 and DRD2 gene polymorphisms in response to haloperidol

P.3.c.044 Influence of ANKK1 and DRD2 gene polymorphisms in response to haloperidol

Influence of DRD2 and ANKK1 polymorphisms on the manifestation of withdrawal syndrome symptoms in alcohol addiction

BackgroundWeinvestigated the relationship between withdrawal syndrome symptoms and dopamine receptor 2 DRD2 gene polymorphisms -141 C I/D (rs1799732) exon 8 G/A (rs6276) and ANKK1 (Ankyrin Repeat and Kinase Domain Containing 1) gene polymorphism Taq 1 A (rs1800497). MaterialA total number of 213 patients who met the ICD 10 criteria for given phenotypes were enrolled in the study. Those phenotypes included: dissocial personality disorder, early onset, alcohol withdrawal syndrome with seizures, alcohol withdrawal syndrome with delirium tremens, and alcohol withdrawal syndrome with seizures and delirium tremens. ResultsOur results show statistically significant associations between SNP in exon 8 A/G in the DRD2 gene and alcohol withdrawal syndrome with seizures, and between SNP in promoter -141 C I/D in the DRD2 gene and early onset of alcohol dependence (AD). The A/A genotype in exon 8 A/G polymorphism seems to be a positive predictive factor for the presence or the lack of seizures in alcohol withdrawal syndrome. The A/G genotype is possibly a protective factor for this AD phenotype. ConclusionsThese results suggest that both investigated DRD2 polymorphisms have an impact onthe AD phenotype. The findings of the presented study reconfirm that dopamine receptor 2 gene polymorphisms are associated with alcohol addiction and alcohol withdrawal syndrome.