Dopamine Receptor Gene Polymorphisms Research Articles

Association between opioid and dopamine receptor gene polymorphisms OPRM1rs1799971, DAT VNTR9-10 repeat allele, DRD1 rs4532 and DRD2 rs1799732 and alcohol dependence: an ethnicity oriented meta-analysis.

We carried out a meta-analysis of four opioid and dopamine candidate gene polymorphisms having conflicting results in prior literature, namely OPRM1 rs1799971, DAT VNTR9-10 repeat, DRD1 rs4532 and DRD2 rs1799732, to clarify their association with alcohol dependence and further stratified results by ethnicity to analyze possible ethnicity-mediated effects. Inclusion criteria: case-control studies assessing the association between OPRM1 rs1799971, DAT VNTR9/10 repeat allele, DRD1 rs4532 and DRD2 rs1799732 with alcohol dependence, with sufficient data available to calculate the odds ratio (OR) within a 95% confidence interval. Exclusion criteria: studies of quantitative measures of alcohol consumption, response to medications or analyses of other markers in the candidate genes, studies without controls, animal studies and lack of genotyping data. Information sources were PubMed, Google Scholar and ScienceDirect databases, all of which were searched for articles published till 2021. Heterogeneity between studies and publication bias, subgroup analyses and sensitivity analyses were carried out. A total of 41 published studies were included in the current meta-analysis. For the OPRM1 gene, there was a statistically significant association in the Asian population with a pooled OR of 1.707 (95% CI, 1.32-2.20 P < 0.0001) and 1.618 (95% CI, 1.16-2.26 P = 0.005) in the additive and dominant genetic models. For DAT VNTR 9/10 repeat, a statistically significant association of the risk vs. common allele was observed in AD with a pooled OR of 1.104 (95% CI, 1.00-1.21 P = 0.046) in the allele model and the additive genetic model in the Caucasian population with pooled OR of 1.152 (95% CI, 1.01-1.31 P = 0.034). Results indicate that some of the effects may be ethnicity-specific. The meta-analysis has been registered in the CRD PROSPERO (CRD42023411576).

Analysis of DRD2 Gene Polymorphism in the Context of Personality Traits in a Group of Athletes.

The presented study showed the relationship between dopamine receptor gene polymorphism and personality traits in athletes training in martial arts. Behavioral modulation resulting from a balance of the neurotransmitters dopamine and norepinephrine to inactivation of the dorsolateral prefrontal cortex and dysregulation of various pathways involved in attention and impulse control processes; Methods: The study was conducted among martial arts athletes. The study group included 258 volunteers and 284 controls. The genetic test was performed using the real-time PCR method; psychological tests were performed using standardized TCI questionnaires. All analyses were performed using STATISTICA 13. Results: Interaction between martial arts and DRD2 rs1799732 (manual) G/-(VIC/FAM)-ins/del and RD- Harm avoidance and Reward Dependence scale were demonstrated. In athletes, a lower Reward Dependence scale score was associated with the DRD2 rs1799732 (manual)-/-polymorphism compared to the control group. Conclusions: It seems justified to study not only genetic aspects related to brain transmission dopamine in martial arts athletes. In the studied athletes, the features related to reward addiction and harm avoidance are particularly important in connection with the dopaminergic reward system in the brain.

Polymorphisms of Dopamine Receptor Genes and Parkinson's Disease: Clinical Relevance and Future Perspectives.

Parkinson’s disease (PD) is a neurodegenerative disease caused by loss of dopaminergic neurons in the midbrain. PD is clinically characterized by a variety of motor and nonmotor symptoms, and treatment relies on dopaminergic replacement. Beyond a common pathological hallmark, PD patients may present differences in both clinical progression and response to drug therapy that are partly affected by genetic factors. Despite extensive knowledge on genetic variability of dopaminergic receptors (DR), few studies have addressed their relevance as possible influencers of clinical heterogeneity in PD patients. In this review, we summarized available evidence regarding the role of genetic polymorphisms in DR as possible determinants of PD development, progression and treatment response. Moreover, we examined the role of DR in the modulation of peripheral immunity, in light of the emerging role of the peripheral immune system in PD pathophysiology. A better understanding of all these aspects represents an important step towards the development of precise and personalized disease-modifying therapies for PD.

Association of dopamine receptor gene polymorphism with the risk of Parkinson's Disease

Introduction: Parkinson's disease is a progressive neurodegenerative disease. Current study is aimed to identify the functional dopamine receptor (DRD) gene polymorphisms DRD1, DRD2, DRD3 and DRD4 involved in PD pathogenesis in south Indian population.

Genetic variants in dopamine pathways affect personality dimensions displayed by patients with eating disorders

We aimed to analyze the association between common polymorphisms in dopamine pathways with personality dimensions frequently present in patients with eating disorders (ED). A total of 324 patients [210 with anorexia nervosa (AN), 80 with bulimia nervosa (BN) and 34 with binge-eating disorder (BED)] were diagnosed according to DSM-5 criteria and interviewed using the EDI 2 and SCL-90R questionnaires at the eating disorders unit. Blood samples were drawn and the DNA screened for polymorphisms in dopamine receptor genes (DRD2 A2/A1 and DRD3 Ser9Gly) and in the dopamine transporter DAT1 10R/9R. AN patients who carried the DRD3 Gly9Gly genotype displayed significantly higher EDI-2 total scores than patients with the Ser9 allele (118.09 ± 8.75 vs. 97.23 ± 2.73, p = 0.010). In these patients, Gly9Gly carriers also showed higher scores in all the individuals' EDI-2 scales. Differences were especially relevant for bulimia (p = 0.004), ineffectiveness (p = 0.044), interpersonal distrust (p = 0.037), interoceptive awareness (p = 0.006) and maturity fears (p = 0.038). Epistasis analyses showed a strong effect of the interaction between DRD3 Ser9Gly and DRD2 A2A1 on the bulimia (p < 0.05), ineffectiveness (p < 0.05) and asceticism (p < 0.01) scales, as well as on the EDI-2 total score (p < 0.05). The scores of the SCL-90R inventory were largely unaffected by the presence of the polymorphisms. Whilst no associations were found for the BN and BED groups, our results suggest that women with AN carrying the homozygous variant Gly9Gly genotype in the dopamine D3 receptor have significantly worse ED-related symptomatology. Level III (evidence obtained from well-designed cohort or case-control analytic studies).

Prediction of sleep side effects following methylphenidate treatment in ADHD youth.

Sleep problems is the most common side effect of methylphenidate (MPH) treatment in ADHD youth and carry potential to negatively impact long-term self-regulatory functioning. This study aimed to examine whether applying machine learning approaches to pre-treatment demographic, clinical questionnaire, environmental, neuropsychological, genetic, and neuroimaging features can predict sleep side effects following MPH administration. The present study included 83 ADHD subjects as a training dataset. The participants were enrolled in an 8-week, open-label trial of MPH. The Barkley Stimulant Side Effects Rating Scale was used to determine the presence/absence of sleep problems at the 2nd week of treatment. Prediction of sleep side effects were performed with step-wise addition of variables measured at baseline: demographics (age, gender, IQ, height/weight) and clinical variables (ADHD Rating Scale-IV (ADHD-RS) and Disruptive Behavior Disorder rating scale) at stage 1, neuropsychological test (continuous performance test (CPT), Stroop color word test) and genetic/environmental variables (dopamine and norepinephrine receptor gene (DAT1, DRD4, ADRA2A, and SLC6A2) polymorphisms, blood lead, and urine cotinine level) at stage 2, and structural connectivities of frontostriatal circuits at stage 3. Three different machine learning algorithms ((Logistic Ridge Regression (LR), support vector machine (SVM), J48) were used for data analysis. Robustness of classifier model was validated in the independent dataset of 36 ADHD subjects. Classification accuracy of LR was 95.5% (area under receiver operating characteristic curve (AUC) 0.99), followed by SVM (91.0%, AUC 0.85) and J48 (90.0%, AUC 0.87) at stage 3 for predicting sleep problems. The inattention symptoms of ADHD-RS, CPT response time variability, the DAT1, ADRA2A DraI, and SLC6A2 A-3081T polymorphisms, and the structural connectivities between frontal and striatal brain regions were identified as the most differentiating subset of features. Validation analysis achieved accuracy of 86.1% (AUC 0.92) at stage 3 with J48. Our results provide preliminary support to the combination of multimodal classifier, in particular, neuroimaging features, as an informative method that can assist in predicting MPH side effects in ADHD.

Polymorphism of Dopamine D2-141C Ins/Del Receptor Gene in Paranoid Schizophrenia and Non Schizophrenia Patients of Batak Ethnicity in Sumatera Utara

Introduction: Schizophrenia is a chronic mental condition which is characterized by reality distortion as well as thought, speech and behavior disorders. Several factors that may cause schizophrenia include genetic abnormalities of dopamine receptors that contribute to disorders in function of the brain, several studies have found an association between schizophrenic and non schizophrenic patients in the dopamine receptor gene polymorphism D2 -141C Ins/Del. Aim: To investigate the relationship of DRD2 -141C Ins/Del gene polymorphism in schizophrenic and non-schizophrenic patients of Batak ethnicity in Sumatera Utara, Indonesia. Methods: This research was done as an unpaired analytical case-control study. The subjects of the study were DNA isolates obtained from 60 patients of paranoid schizophrenia and 54 non-schizophrenia of Batak ethnicity in Sumatera Utara, Indonesia. PCR examination was performed on the DNA isolates to examine D2 -141C Ins/Del dopamine receptor gene polymorphism. The data collected were then analyzed statistically. Result: In this study, three variants of DRD2 gene polymorphism (I/D: 304bp, 160bp, 144bp), (I/I: 160bp, 144bp), (D/D: 304bp) was identified. In both schizophrenic and non-schizophrenic patients, the highest I/D genotypes were identified (71.7%) and (63%) , and the least D/D genotypes were identified (6.7%) and (7.4%) with p = 0.726. Based on the allele distribution there was no difference of risk on allele D and allele I on the cause factor of schizophrenia (OR: 1.13; 95% CI: 0.66-1.92). According to Hardy-Weinberg Equilibrium law, both schizophrenic and non schizophrenic patients of Batak ethnicity in Sumatera Utara is in disequilibrium p = 0.0002 and p = 0.0057 with significance of p <0,05. Conclusion: There is no significant association between genotypic distribution and DRD2 -141C Ins/Del gene alleles in schizophrenic and non schizophrenic patients.

Sex-specific association of a common GNAS polymorphism with self-reported cognitive empathy in healthy volunteers.

BackgroundIn a recent study, we found associations of a common oxytocin receptor (OXTR) polymorphism with inter-individual differences in empathy, especially with emotional empathy in women. Many other studies found specific associations of oxytocin, arginine-vasopressin, serotonin and dopamine receptor gene polymorphisms with various aspects of trait empathy. As all these receptors belong to the guanine-binding protein (G protein) coupled receptor family, it is a reasonable assumption, that alterations in genes encoding G protein subunits also influence the signal transduction in empathy related circuits. However, to the best of our knowledge, these genomic variations have not yet been studied in genetic research on empathy.MethodsHere, we analysed associations of a common polymorphism of the GNAS gene (C393T) in a previously characterized sample of 421 healthy blood donors (231 M, 190 F; age 18–74). The GNAS gene encodes the G protein adenylyl cyclase stimulator (Gαs) G protein subunit, which activates cyclic adenosine monophosphate (cAMP)-dependent pathways by stimulating the adenylyl cyclase. Cognitive and emotional aspects of dispositional empathy were tested using Davis’ Interpersonal Reactivity Index (IRI).ResultsIn the complete sample, associations of C393T genotype with IRI empathy scores, including cognitive empathy (p = 0.055) and perspective taking (p = 0.057) scores did not reach a level of significance. None of the IRI scores was near to being significantly associated with C393T genotype for men alone. In females, however, genotype was significantly associated with cognitive empathy (r = -.204, p = 0.005) and perspective taking (r = -.209, p = 0.004), accounting for 4.2% and 4.4% of variability. The association of genotype with perspective taking remained significant after adjustment for multiple comparisons (p = 0.045). The 393C-allele, which had been identified as a risk factor in several medical conditions such as hypertension, obesity and diabetes, was associated with higher cognitive empathy compared to the T allele in our sample.ConclusionsThe results suggest a significant association of GNAS C393T genotypes with the cognitive empathic capacity of perspective taking. This association could only be found in female participants.

Association between dopamine receptor gene polymorphisms and effects of risperidone treatment: A systematic review and meta-analysis.

The effect of risperidone treatment in patients with schizophrenia varies according to the dopamine receptor genes. This study aimed to evaluate the relationship between genes of the dopamine receptors (D1, D2, and D3) and the effect of risperidone treatment. Three electronic databases (PubMed, Embase, and Cochrane Library) were searched for relevant cohort or case-control studies published before 9 May 2018. A systematic review and meta-analysis was performed for qualitative and quantitative assessment of the relationship between the dopamine receptors D1, D2, and D3 (DRD1, 2, and 3) and the effect of risperidone treatment. The summary odds ratio (OR) and weighted mean difference (WMD) in a random-effects model were used to measure these relationships. Twelve studies involving 24 SNPs were included. DRD2 (Ser311Cys, rs1801028 Ser/Ser) significantly lowered the improvement rate (determined by the PANSS score) unlike Ser/Cys (WMD: -11.58, 95% CI: -17.35 to -5.18). For Asian patients, A241G (rs1799978) AA carriers showed greater improvement after risperidone therapy (P<0.05). The polymorphisms of 141C Ins/Del (rs1799732), T939C (rs6275), rs6277, and TaqID (rs1800498) may also influence the treatment effect. TaqIA (rs1800497) and TaqIB (rs17294542) were not associated with the rate of response to risperidone. DRD3 was not associated with an improvement in the PANSS total score; however, Ser9Gly might be related to a change in negative symptoms. No significant effect of DRD1 (rs5326, rs4867798, rs4532, and rs11749676) was found. Our result supported the hypothesis that DRD2 affected risperidone treatment. DRD1 had no significant effect on the response to risperidone, whereas DRD3 might be associated with an improvement in negative symptoms. Larger observational studies are warranted to verify these findings and identify other genetic factors involved.

Preliminary Evidence for an Association Between Variants of the Catechol-O-Methyltransferase (COMT) Gene and Premature Ejaculation

BackgroundStudies have suggested that dopamine plays a role in the neurobiological mechanism that triggers ejaculation, leading scientists to hypothesize that dopamine-related genetic polymorphisms could contribute to symptoms of premature ejaculation (PE). AimTo investigate associations between dopamine receptor and catechol-O-methyltransferase (COMT; an enzyme involved in the catabolism of dopamine) gene-linked polymorphisms and PE. MethodsPE status in patient groups was determined by clinical diagnosis performed by a physician specializing in sexual medicine. Self-reported PE symptoms from a validated questionnaire also were reported. Saliva samples were collected from 149 patients with PE and 1,022 controls from a population-based sample. In total, we tested associations between PE and 11 single-nucleotide polymorphisms in the dopamine receptor D1, D2, and D3 genes and in the COMT gene. OutcomesWe found no associations between dopamine receptor gene polymorphisms and PE, but 2 COMT-linked loci (rs4680 and rs4818) had significant associations after correction for multiple testing. Results1 COMT gene-linked locus that was associated with PE symptoms in the present study, rs4680, is a well-documented functional polymorphism that causes a valine-to-methionine substitution. The other polymorphism, rs4818, is in high linkage disequilibrium with the rs4680 locus, indicating that they capture the same effect. Surprisingly, the rs4680 variant that was statistically significantly more prevalent in the PE group (ie, the valine-encoding allele) has been associated with higher enzymatic activity and therefore lower synaptic dopamine levels. Clinical TranslationDrugs targeting the dopaminergic system could affect PE symptoms. Strengths and LimitationsNo replication sample was available for the present study; thus, our findings should be interpreted with caution. Moreover, a limitation of our study is the small sample in the context of genetic association studies (although it should be mentioned that genetically informative samples with phenotypic information about PE symptoms are scarce, and most previous genetic association studies of PE have used samples of similar or smaller size). However, our results are plausible: we report an association between one of the most extensively studied and understood genetic polymorphisms in psychiatric research and PE, and our results are in line with the long-standing hypothesis that dopamine influences human ejaculatory function. ConclusionsWe report an association between 2 COMT gene-linked loci and PE symptoms, but our results should be treated with caution until independently replicated.Jern P, Johansson A, Strohmaier J, et al. Preliminary Evidence for an Association Between Variants of the Catechol-O-Methyltransferase (COMT) Gene and Premature Ejaculation. J Sex Med 2017;14:1558–1565.

CAMP levels in lymphocytes and CD4+ regulatory T-cell functions are affected by dopamine receptor gene polymorphisms.

The neurotransmitter dopamine (DA) has prominent effects in the immune system and between the immune cells, CD4+ regulatory T (Treg) lymphocytes, a specialized T-cell subset crucial for the control of immune homeostasis, are especially sensitive to DA. Dopaminergic receptors (DR) are grouped into two families according to their pharmacological profile and main second messenger coupling: the D1 -like (D1 and D5 ), which activate adenylate cyclase, and the D2 -like (D2 , D3 and D4 ), which inhibit adenylate cyclase and exist in several variants that have been associated to clinical conditions such as schizophrenia, bipolar disorder, substance abuse and addiction. We aimed to examine, in venous blood samples from healthy volunteers, the relationship between the arbitrary DR score and DR functional responses in human lymphocytes. All the samples were genotyped for selected DR gene variants (DRD1: rs4532 and rs686; DRD2: rs1800497 and rs6277; DRD3: rs6280; DRD4: rs747302 and seven 48-base pair variable number tandem repeat (VNTR)) and a DR score was attributed to each participant. We have also tested whether DR gene polymorphisms might affect Treg cell ability to suppress effector T-cell function. To our knowledge, this is the first study showing a correlation between DR gene variants and human T lymphocyte function. The main results are that both D1 -like and D2 -like DR are functionally active in human lymphocytes, although the D1 -like DR stimulation results in stronger effects in comparison to the D2 -like DR stimulation. In addition, it seems that the DR genetic profile may affect the ability of lymphocytes to respond to dopaminergic agents. More investigations are needed about the possible clinical relevance of such findings.

Risperidone-Induced Adverse Drug Reactions and Role of DRD2 (-141 C Ins/Del) and 5HTR2C (-759 C>T) Genetic Polymorphisms in Patients with Schizophrenia.

Objective:To determine the adverse drug reaction (ADR) profile of risperidone and their association with dopamine (DRD2 − 141 C Ins/Del/rs1799732) and serotonin receptor (5HTR2C −759 C>T/rs3813929) gene polymorphisms in patients with schizophrenia.Materials and Methods:The study was conducted among 289 patients who were diagnosed with schizophrenia and were on treatment with risperidone (4–8 mg/day)-based therapy for a minimum of 4 weeks. Genotyping was carried by real-time quantitative polymerase chain reaction. All the patients were observed for the occurrences of ADRs during the study. Changes in prolactin levels and body weight were analyzed for a subgroup of 102 and 97 patients, respectively.Results:Risperidone-induced extrapyramidal symptoms (EPSs) were seen in 36.7% of patients. Among them, tremors were the most common symptom 31.8%. Risperidone-induced hyperprolactinemia and weight gain were seen in 87.2% and 53.6% in subgroup patients. Adverse effects such as sedation, gastrointestinal effects, and amenorrhea were seen in 9.7% (28/289), 5.1% (15/289), and 6.1% (7/114), respectively. Occurrence of DRD2 − 141 Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels in response to risperidone (odds ratio [OR] = 10.45; 95% confidence interval = 1.29–84.89, P = 0.004). No such association was observed with 5HTR2C (−759 C>T) polymorphism. Weight gain and EPS were not associated with the above genetic polymorphisms.Conclusion:Hyperprolactinemia, weight gain, and EPSs (>36.7%) were common adverse effects of risperidone. DRD2 – 141C Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels (OR = 10.45) in response to risperidone.

Polymorphisms of Dopamine Receptor Genes and Risk of L-Dopa–Induced Dyskinesia in Parkinson’s Disease

L-dopa–induced dyskinesia (LID) is a frequent motor complication of Parkinson’s disease (PD), associated with a negative prognosis. Previous studies showed an association between dopamine receptor (DR) gene (DR) variants and LID, the results of which have not been confirmed. The present study is aimed to determine whether genetic differences of DR are associated with LID in a small but well-characterized cohort of PD patients. To this end we enrolled 100 PD subjects, 50 with and 50 without LID, matched for age, gender, disease duration and dopaminergic medication in a case-control study. We conducted polymerase chain reaction for single nucleotide polymorphisms (SNP) in both D1-like (DRD1A48G; DRD1C62T and DRD5T798C) and D2-like DR (DRD2G2137A, DRD2C957T, DRD3G25A, DRD3G712C, DRD4C616G and DRD4nR VNTR 48bp) analyzed genomic DNA. Our results showed that PD patients carrying allele A at DRD3G3127A had an increased risk of LID (OR 4.9; 95% CI 1.7–13.9; p = 0.004). The present findings may provide valuable information for personalizing pharmacological therapy in PD patients.

Dopaminergic Genetic Polymorphisms Predict Rule-based Category Learning.

Dopaminergic genes play an important role in cognitive function. DRD2 and DARPP-32 dopamine receptor gene polymorphisms affect striatal dopamine binding potential, and the Val158Met single-nucleotide polymorphism of the COMT gene moderates dopamine availability in the pFC. Our study assesses the role of these gene polymorphisms on performance in two rule-based category learning tasks. Participants completed unidimensional and conjunctive rule-based tasks. In the unidimensional task, a rule along a single stimulus dimension can be used to distinguish category members. In contrast, a conjunctive rule utilizes a combination of two dimensions to distinguish category members. DRD2 C957T TT homozygotes outperformed C allele carriers on both tasks, and DARPP-32 AA homozygotes outperformed G allele carriers on both tasks. However, we found an interaction between COMT and task type where Met allele carriers outperformed Val homozygotes in the conjunctive rule task, but both groups performed equally well in the unidimensional task. Thus, striatal dopamine binding may play a critical role in both types of rule-based tasks, whereas prefrontal dopamine binding is important for learning more complex conjunctive rule tasks. Modeling results suggest that striatal dopaminergic genes influence selective attention processes whereas cortical genes mediate the ability to update complex rule representations.

Polymorphisms of dopamine receptor genes are associated to increased risk of visual hallucinations in Italian Parkinson's disease patients

Polymorphisms of dopamine receptor genes are associated to increased risk of visual hallucinations in Italian Parkinson's disease patients

Looking for reward in all the wrong places: dopamine receptor gene polymorphisms indirectly affect aggression through sensation-seeking

ABSTRACTIndividuals with genotypes that code for reduced dopaminergic brain activity often exhibit a predisposition toward aggression. However, it remains largely unknown how dopaminergic genotypes may increase aggression. Lower-functioning dopamine systems motivate individuals to seek reward from external sources such as illicit drugs and other risky experiences. Based on emerging evidence that aggression is a rewarding experience, we predicted that the effect of lower-functioning dopaminergic functioning on aggression would be mediated by tendencies to seek the environment for rewards. Caucasian female and male undergraduates (N = 277) were genotyped for five polymorphisms of the dopamine D2 receptor (DRD2) gene; they reported their previous history of aggression and their dispositional reward-seeking. Lower-functioning DRD2 profiles were associated with greater sensation-seeking, which then predicted greater aggression. Our findings suggest that lower-functioning dopaminergic activity puts individuals at risk for violence because it motivates them to experience aggression’s hedonically rewarding qualities.

Genetic and Functional Analysis of Polymorphisms in the Human Dopamine Receptor and Transporter Genes in Small Cell Lung Cancer

The regulatory role of dopamine (DA) in endocrine, cardiovascular and renal functions has been extensively studied and used for clinical purposes. More recently DA has been indicated as a regulatory molecule for immune cells and malignant cell proliferation. We assessed the expression and the functional role DA, DA receptors, and transporters in primary small cell lung cancer (SCLC). By HPLC DA plasma levels were more elevated in SCLC patients in comparison with NSCLC patients and healthy controls. SCLC cell expressed DA D1- and D2-like receptors and membrane and vesicular transporters at protein and mRNA levels. We also investigated the effects of independent D1- or D2-like receptor stimulation on SCLC cell cultures. DA D1 receptor agonist SKF38393 induced the increase of cAMP levels and DARPP-32 protein expression without affecting SCLC growth rate. Cell treatment with the DA D1 receptor antagonist SCH23390 inhibited SKF38393 effects. In contrast, the DA D2 receptor agonist quinpirole (10 μM) counteracted, in a dose and time dependent way, SCLC cell proliferation, it did not affect cAMP levels and decreased phosphorylated AKT that was induced by DA D2 receptor antagonist sulpiride. However, in only one SCLC line, stimulation of DA D2 receptor failed to inhibit cell proliferation in vitro. This effect was associated to the existence of rs6275 and rs6277 polymorphisms in the D2 gene. These results gave more insight into DA control of lung cancer cell behavior and suggested the existence of different SCLC phenotypes.

Influence of dopamine receptor gene polymorphisms on circulating T lymphocytes: A pilot study in healthy subjects

Dopamine is a key transmitter in the neuroimmune network, acting through five dopaminergic receptors (DR): the D1-like D1 and D5 and the D2-like D2, D3 and D4. Several DR gene variants exist and may affect DR expression and activity. We assessed total lymphocytes, CD3+, CD4+ and CD8+ T lymphocytes in peripheral blood of healthy subjects and their association with selected DR gene variants (DRD1 rs4532 and rs686, DRD5 rs6283, DRD2 rs1800497 and rs6277, DRD3 rs6280 and rs1800828, DRD4 rs747302 and 7 48-base pair VNTR). DRD1 rs4532 and rs686 and DRD5 rs6283 were associated with total lymphocytes, and with CD3+ and CD4+ (but not CD8+) T lymphocytes, while none of the D2-like DR gene variants showed any association with lymphocyte counts. An arbitrary score based on the activity of D1-like vs D2-like DR correlated with total lymphocytes, CD3+ and CD4+ T cells (but not with CD8+ T cells). The association between D1-like DR gene variants and lymphocyte count, and in particular with CD4+ (but not CD8+) T lymphocytes, may imply a functional prevalence of D1-like over D2-like DR in CD4+ T cells. This is the first study showing an influence of DR gene polymorphisms on lymphocyte count, and in particular on CD4+ T cells. Future studies should address the possible association between DR gene variants and the immune function in health and disease. The relevance of these findings for the immune effects of dopaminergic agents should be also carefully examined.

Suicidal behavior and haplotypes of the dopamine receptor gene (DRD2) and ANKK1 gene polymorphisms in patients with alcohol dependence--preliminary report.

Suicide is a significant public health issue and a major cause of death throughout the world. According to WHO it accounts for almost 2% of deaths worldwide. The etiology of suicidal behavior is complex but the results of many studies suggest that genetic determinants are of significant importance. In our study,- we have analyzed selected SNPs polymorphisms in the DRD2 and ANKK1 genes in patients with alcohol dependence syndrome (169 Caucasian subjects) including a subgroup of individuals (n = 61) who have experienced at least one suicide attempt. The aim of the study was to verify if various haplotypes of selected genes, comprising Taq1A, Taq1B, and Taq1D single nucleotide polymorphisms (SNP), play any role in the development of alcohol dependence and suicidal behavior. The control group comprised 157 unrelated individuals matched for ethnicity, gender,- and age and included no individuals with mental disorders. All subjects were recruited in the North West region of Poland. The study showed that alcohol dependent subjects with a history of at least one suicidal attempt were characterized by a significantly higher frequency of the T-G-A2 haplotype when compared to individuals in whom alcohol dependence was not associated with suicidal behavior (p = 0.006). It appears that studies based on identifying correlation between SNPs is the future for research on genetic risk factors that contribute to the development of alcohol addiction and other associated disorders. To sum up, there is a necessity to perform further research to explain dependencies between the dopaminergic system, alcohol use disorders and suicidal behavior.

Association study of dopamine receptor genes polymorphism with cognitive functions in bipolar I disorder patients

ObjectiveTo determine the correlation among the polymorphisms of dopamine receptor genes, cognitive function of Bipolar disorder (BD) patients, and BD. MethodsTwenty-three Single Nucleotide Polymorphisms (SNPs) of dopamine receptor genes were genotyped using Illumina GoldenGate genotyping assay in 375 patients with bipolar I disorder (BD-I) (patients group) and 475 healthy controls (control group). Cognitive function tests were performed in 158 patients who were clinically stable and 307 healthy controls who were matched with the patients in age, sex, and education. ResultsThe allele frequencies of rs3758653 in the promoter region of the DRD4 gene were significantly different between patients group and control group (χ2=9.386, Corrected P=0.046). This significant difference was also observed between BD-I patients with psychotic symptoms and healthy controls (χ2=9.27, Corrected P=0.049). Patients with BD-I performed significantly worse than healthy controls in all cognitive domains (p<0.01) except TMTA errors and illegal time. Significant interactions between polymorphisms of rs5326 in DRD1 gene and phenotype (affected or unaffected with BD-I) were found in non-perseverative errors (β=3.20 and Corrected P=0.0034) on the Wisconsin Card Sorting Test (WCST). The allele of this SNP denoted the positive effect on the WCST non-perseverative errors in BD-I patients group (β=2.80 and Corrected P=0.017). The genotypic association analyses also supported the findings (F=4.24 and P=0.007), but this effect was not found in controls. LimitationsThe sample size was relatively small and the SNP coverage was limited, making it very important to be cautious when drawing a conclusion. ConclusionsDRD4 gene may play an important role in psychotic symptomatology rather than in unique diagnosis, BD, for example. A genetic association exists between DRD1 gene and impaired cognition in BD.