D2 Receptor Polymorphisms Research Articles

Attention Deficit Hyperactivity Disorder and dopamine D4 receptor (DRD4) polymorphisms in South Indian population

Objectives Four decades of research have found that Dopamine D4 Receptor (DRD4) is the major candidate gene however, few studies have supported the association between the DRD4 exon III long seven repeat allele and Attention Deficit Hyperactive Disorder (ADHD). Two Indian studies had shown there is an association between DRD4 7 repeat allele; hence, we investigated in the south Indian population. AIMS: To study the association of DRD4-EXON-3-7R long allele and minor physical anomalies with ADHD in comparison to age & sex-controlled normal subjects with no evidence of ADHD. settings and design-cross-sectional case-control study for two years at National Institute of Mental Health And NeuroSciences, Bangalore. Material and Methods 60 children with ADHD and 60 healthy children of 4-16 years of age group were recruited after informed consent. Assessed by DSMIV-TR, ADHD RS IV HOME VERSION 18 items, comorbidities by detailed interview of child and parents using Mini-International Neuropsychiatric Interview for Children & Adolescents (M.I.N.I). Kid for minor congenital anomalies modified waldrop scale & for the perinatal complications, Lewis Murray Obstetrics Complication Scales were applied. For the family history family interview for genetic study, global functioning was measured by children global assessment scale, neuropsychological tests of response inhibition test were used and blood samples was collected for genotyping. Results The genotype 2 2,2 4 ,4 4,4 5,4 7 repeat allele has shown equal distribution between cases and controls with p-value 0.492 with no significance. Conclusion There is no association between DRD4 EXON-3-7R long allele gene polymorphism and ADHD in South Indian population. DRD4 7R could be having influence on minor physical anomalies in ADHD.

Polimorfisme Gen DRD2 rs1799732 (-141c) Terhadap Terapi Aripiprazole pada Pasien Skizofrenia

The polymorphism rs1799732 (-141C) is located in the 5 'promoter region of DRD2, where these SNPs can influence modulation of transcription activity and D2 receptor density. This study aims to provide a literature review of the polymorphism rs1799732 (-141C) because this gene polymorphism is the most common gene polymorphism in the world related to schizophrenia. This gene polymorphism is known to play a role in the variability of response to aripiprazole antipsychotic therapy in schizophrenic patients. The type of review used in this article is in the form of a literature review of 38 literature from various journals and textbooks. Schizophrenia is a disease that can affect the brain. In the brain there is a chemical delivery of messages that will forward messages around the brain. In schizophrenic patients, dopamine is excessive, while dopamine levels play an important role in feelings of pleasure and experiences of different moods. If dopamine levels are imbalanced, sufferers can experience both positive and negative symptoms. The hypothesis states that excessive dopaminergic activity can lead to schizophrenia. The dopaminergic system plays an important role as a modulator of affective and cognitive functions. Dopamine D2 receptor polymorphism is known to be a risk factor for schizophrenia. Polymorphisms are determinants of clinical symptoms and can play a role in the effectiveness and side effects of antipsychotics, including aripiprazole. Aripiprazole is a second-generation antipsychotic, an antipsychotic with partial agonist activity against dopamine D2.

Hypomania and saccadic changes in Parkinson\u2019s disease: influence of D2 and D3 dopaminergic signalling

In order to understand the influence of two dopaminergic signalling pathways, TaqIA rs1800497 (influencing striatal D2 receptor density) and Ser9Gly rs6280 (influencing the striatal D3 dopamine-binding affinity), on saccade generation and psychiatric comorbidities in Parkinson’s disease, this study aimed to investigate the association of saccadic performance in hypomanic or impulsive behaviour in parkinsonian patients; besides we questioned whether variants of D2 (A1+/A1−) and D3 (B1+/B1−) receptor polymorphism influence saccadic parameters differently, and if clinical parameters or brain connectivity changes modulate this association in the nigro-caudatal and nigro-collicular tract. Initially, patients and controls were compared regarding saccadic performance and differed in the parameter duration in memory-guided saccades (MGS) and visually guided saccades (VGS) trials (p < 0.0001) and in the MGS trial (p < 0.03). We were able to find associations between hypomanic behaviour (HPS) and saccade parameters (duration, latency, gain and amplitude) for both conditions [MGS (p = 0.036); VGS (p = 0.033)], but not for impulsive behaviour. For the A1 variant duration was significantly associated with HPS [VGS (p = 0.024); MGS (p = 0.033)]. In patients with the B1 variant, HPS scores were more consistently associated with duration [VGS (p = 0.005); MGS (p = 0.015), latency [VGS (p = 0.022)]] and amplitude [MGS (p = 0.006); VGS (p = 0.005)]. The mediation analysis only revealed a significant indirect effect for amplitude in the MGS modality for the variable UPDRS-ON (p < 0.05). All other clinical scales and brain connectivity parameters were not associated with behavioural traits. Collectively, our findings stress the role of striatal D2 and D3 signalling mechanisms in saccade generation and suggest that saccadic performance is associated with the clinical psychiatric state in Parkinson’s disease.

Association of dopamine D2 receptor gene polymorphisms with prolactin levels related to risperidone treatment: A systematic review and meta-analysis.

Dopamine D2 receptor (DRD2) polymorphisms are inconsistently associated with elevated prolactin levels related to risperidone treatment. The aim of this systematic review and meta-analysis was to investigate whether DRD2 polymorphisms could modulate prolactin levels in patients treated with risperidone. Three electronic databases (PubMed, EMBASE and the Cochrane Library) were searched for studies investigating the effect of DRD2 polymorphisms on prolactin levels in patients treated with risperidone until May 2018. Summary standard mean differences (SMDs) and 95% confidence intervals (CIs) were calculated with Hedges' g tests for effect estimates using random effects models. The heterogeneity, sensitivity, univariable meta-regression, subgroup analyses and publication biases were calculated. After initially identifying 886 studies, 772 patients from eight studies were included. Summary SMDs indicated that compared with A1 non-carriers, Taq1A A1 carriers did not have different risperidone-related prolactin levels (SMD: 0.13; 95% CI: -0.18 to 0.43; P=0.423) among patients with schizophrenia (SCZ; SMD: 0.07; 95% CI: -0.14 to 0.29; P=0.505) or among those without SCZ (SMD: 0.16; 95% CI: -0.39 to 0.71; P=0.562). There was no significant difference between Del carriers and Del non-carriers with regard to risperidone-related prolactin levels (SMD: -0.00; 95% CI: -0.59 to 0.58; P=0.996). In an Asian subgroup analysis, we also noted that compared with Taq1A A1A2 carriers, Taq1A A1A1 carriers had lower prolactin levels (SMD: -0.34; 95% CI: -0.66 to -0.02; P=0.040). However, there was no significant difference in prolactin levels between A1A1 carriers and A2A2 carriers (SMD: -0.27; 95% CI: -0.60 to 0.05; P=0.098), or between A2 carriers and A2 non-carriers (SMD: 0.29; 95% CI: -0.01 to 0.59; P=0.059). Based on univariable meta-regression analyses, the effects of publication year, study design, ethnicity, comparison groups and study quality could bias the identified association of DRD2 Taq1A with risperidone-related prolactin levels. The findings of this study suggest that there is no significant difference between Taq1A A1 carriers and non-A1 carriers with regard to risperidone-related prolactin levels. As there were few A1 homozygotes, large prospective studies with robust designs are still needed to investigate whether A1A1 could affect risperidone-related prolactin levels in the Asian population.

Dopamine D2 receptor polymorphism (C957T) is associated with sugar consumption and triglyceride levels in West Mexicans.

Genetic variations in the dopamine receptor D2 (DRD2) may alter dopamine signaling and modify the rewarding effects of food. This study aimed to analyze the association of the C957T DRD2 polymorphism with sugar consumption in West Mexican subjects. In a cross-sectional and analytical study, a total of 215 Mexican subjects were enrolled. DRD2 genotyping was performed by an allelic discrimination assay. Habitual dietary intake and the biochemical profile were evaluated. Genotype frequencies of the C957T DRD2 polymorphism were CC (12.1%), CT (40.9%) and TT (47.0%). Carriers of the CC genotype had a higher intake of sugar (g/day) than heterozygotes (67.4 g vs. 41.3 g, p = 0.001) and TT homozygotes (67.4 g vs. 45.2 g, p = 0.004). Also, the habitual consumption of soda (daily or at least 3 times per week) was more frequent among CC genotype carriers compared with heterozygotes (81% vs. 51%, p = 7.5 × 10-6) and TT homozygotes (81% vs. 57%, p = 2.4 × 10-4). Furthermore, the CC genotype was associated with elevated serum triglyceride levels (>150 mg/dL) than the CT genotype (OR = 2.80, 95% CI 1.08-7.24, p = 0.034). In conclusion, our results suggest a genetic background associated with sugar consumption among West Mexicans, which may contribute to increases in serum triglyceride levels.

Dopamine D2 \u2212141C Ins/Del and Taq1A polymorphisms, body mass index, and prediction error brain response

The prediction error model is a widely used paradigm that is conceptually based on neuronal dopamine function. However, whether dopamine receptor gene alleles contribute to human neuroimaging prediction error results is uncertain. Recent research implicated the dopamine D2 receptor in behavior response during a prediction error paradigm and we expected that polymorphisms of that receptor would contribute to prediction error brain response. In this study, healthy female participants in the early follicular phase of the menstrual cycle underwent a taste prediction error paradigm during functional magnetic resonance imaging. Participants were also genotyped for dopamine receptor polymorphisms. Our data suggest that the dopamine D2 receptor −141C Ins/Del and Taq1A polymorphisms together with body mass index selectively explain putamen prediction error response. This was true using a region of interest analysis as well as for a whole-brain analysis (FWE corrected). Polymorphisms for dopamine D1 or D4 receptors, dopamine transporter, or COMT did not significantly contribute to prediction error activation. The prediction error model is a computational reward-learning paradigm that is important in psychiatric research and has been associated with dopamine. The results from this study indicate that dopamine D2 receptor polymorphisms together with body mass index are important determinants to include in research that tests prediction error response of the brain. Psychiatric disorders are frequently associated with elevated or reduced body weight. Adding BMI to genetic information in brain-imaging studies that use reward and the prediction error paradigm may be important to increase validity and reliability of results.

Influence of CYP1A2, adenosine A2A receptor and dopamine D2 receptor polymorphisms on the changes of blood pressure and calculation speed by caffeine intake

Influence of CYP1A2, adenosine A2A receptor and dopamine D2 receptor polymorphisms on the changes of blood pressure and calculation speed by caffeine intake

Does DRD2 polymorphism influence the clinical characteristics of prolactinoma?

ObjectivesGenetic alterations explaining the clinical variability of prolactinomas still could not be clarified and dopamine D2 receptor (DRD2) polymorphism is a putative candidate for the variable response to dopaminergic treatment. The present study was conducted to investigate the influence of DRD2 TaqI A polymorphism on initial and follow-up characteristics of prolactinoma. Patients and methodsSeventy-two patients with prolactinoma and 98 age and gender matched control subjects were recruited to the case-control study. Serum prolactin levels were assessed by enzyme-linked immunosorbent assay and DRD2 polymorphism was determined by polymerase chain reaction and restriction length polymorphism analysis. ResultsDecrease of prolactin levels and the tumor shrinkage after cabergoline treatment were 93.9±5.9% and 58.3±33.1% in microadenomas and 96.1±6.1% and 51.7±29.3 in macroadenomas (P=0.02 and P>0.05, respectively). We observed no significant difference for DRD2 genotypes and the alleles between the patients and healthy group (P>0.05). Prolactin levels before treatment were correlated with tumor diameter before and after treatment and the percentage of prolactin decrease with treatment (P<0.001 r=0.58, P<0.001 r=0.40 and P<0.001 r=0.47, respectively). Tumor diameter before the treatment was also correlated with the tumor diameter after the treatment (P<0.001 r=0.64) and the percentage of prolactin decrease (P=0.01 r=0.30). However, no significant association was found between characteristics of prolactinoma and DRD2 genotypes and alleles (P>0.05). ConclusionThis study revealed that DRD2 TaqI A receptor polymorphism was not associated with the development of prolactinoma and its clinical characteristics. Future studies are needed to clarify the clinical implications of genetic alterations in prolactinoma.

Association between the traditional Chinese medicine pathological factors of opioid addiction and DRD2/ANKK1 TaqIA polymorphisms.

BackgroundAs we known, Traditional Chinese Medicine (TCM) helps to prevent the relapse of drug addiction. However, the scientific basis of TCM remains unclear because of limitations of current reductionist approaches. We aimed to explore the possible mechanism of how ANKK1 TaqIA (A1/A2) [rs1800497(T/C)] affects the relapse of opioid addiction on the perspective of Chinese traditional medicine.MethodsThe ANKK1 TaqIA (A1/A2) [rs1800497(T/C)] of the dopamine D2 receptor (DRD2) polymorphisms were genotyped in a case–control sample consisting of 347 opioid addicts and 155 healthy controls with RT-PCR and the TCM pathological factors were collected by means of Syndrome Elements Differentiation in the case–control sample.ResultsDRD2/ANKK1 TaqIA Polymorphisms has no relation with opioid addiction relapse; but for those who were diagnosed with phlegm syndrome, DRD2/ANKK1 TaqIA Polymorphisms affect the replapse of apioid addiction (P < 0.05).ConclusionsDRD2/ANKK1 TaqIA is associated with opioid addict and it is obvious in opioid addicts who suffer from the phlegm syndrome.

Dopamine D4 receptor polymorphism and sex interact to predict children's affective knowledge.

Affective knowledge, the ability to understand others’ emotional states, is considered to be a fundamental part in efficient social interaction. Affective knowledge can be seen as related to cognitive empathy, and in the framework of theory of mind (ToM) as affective ToM. Previous studies found that cognitive empathy and ToM are heritable, yet little is known regarding the specific genes involved in individual variability in affective knowledge. Investigating the genetic basis of affective knowledge is important for understanding brain mechanisms underlying socio-cognitive abilities. The 7-repeat (7R) allele within the third exon of the dopamine D4 receptor gene (DRD4-III) has been a focus of interest, due to accumulated knowledge regarding its relevance to individual differences in social behavior. A recent study suggests that an interaction between the DRD4-III polymorphism and sex is associated with cognitive empathy among adults. We aimed to examine the same association in two childhood age groups. Children (N = 280, age 3.5 years, N = 283, age 5 years) participated as part of the Longitudinal Israel Study of Twins. Affective knowledge was assessed through children’s responses to an illustrated story describing different emotional situations, told in a laboratory setting. The findings suggest a significant interaction between sex and the DRD4-III polymorphism, replicated in both age groups. Boy carriers of the 7R allele had higher affective knowledge scores than girls, whereas in the absence of the 7R there was no significant sex effect on affective knowledge. The results support the importance of DRD4-III polymorphism and sex differences to social development. Possible explanations for differences from adult findings are discussed, as are pathways for future studies.

The Dopamine D2 Receptor Polymorphism (DRD2 TaqIA) Interacts with Maternal Parenting in Predicting Early Adolescent Depressive Symptoms: Evidence of Differential Susceptibility and Age Differences.

Most gene-environment interaction research on depression has largely focused on negative environment and to a lesser extent on positive environment. Moreover, to date few studies have directly examined G × E at different periods in development, particularly during early adolescence. The present study addressed these issues by examining the concurrent and prospective longitudinal effects of maternal parenting, DRD2 TaqIA polymorphism, and their interaction on adolescent depressive symptoms in a sample of 1026 Chinese adolescents (Mage = 11.33 ± 0.47 years at T1, 50.3% girls) in a three-wave longitudinal study from age 11 to 13. Results indicated that maternal positive and negative parenting significantly concurrently predicted adolescent depressive symptoms at all three waves, whereas TaqIA polymorphism had no main effect on depressive symptoms. TaqIA polymorphism interacted with negative parenting in predicting concurrent depressive symptoms at age 11 and 12. A1 carriers were more susceptible to negative parenting compared to A2A2 homozygotes, such that adolescents carrying A1 alleles experiencing high negative parenting reported more depressive symptoms but fared better when experiencing low negative parenting. However, the interaction became nonsignificant at age 13, indicating the interaction of TaqIA polymorphism and maternal parenting may vary with development. Also, there was no G × E effect on longitudinal change in depression. The findings provided evidence in support of the differential susceptibility hypothesis and shed light on the potential for dynamic change in gene-environment interactions over development.

Association between DRD2 (rs1799732 and rs1801028) and ANKK1 (rs1800497) polymorphisms and schizophrenia: a meta-analysis.

The role of dopamine D2 receptor (DRD2) polymorphisms in schizophrenia remains controversial. We performed a meta-analysis to determine whether DRD2 polymorphisms influence the risk of schizophrenia and examined the relationship between rs1799732, rs1801028, and rs1800rs028 an23381d rs1800497 genetic variants and the etiology of schizophrenia. 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 76 studies with 16096 cases and 18965 controls were included. Specifically, 24 studies with 6075 cases and 6643 controls involved rs1799732, 36 studies with 8043 cases and 10194 controls involved rs1801028 and 16 studies with 1978 cases and 2128 controls involved rs1800497. No significant associations were observed between rs1799732 and rs1800rs732 and rs1800497 and schizophrenia. The rs1801028 locus was associated with schizophrenia, with a pooled OR of 1.221 (95% CI = 1.037-1.438, P = 0.016). This meta-analysis indicates that the rs1801028 locus may be associated with schizophrenia. These data provide possible references for future case-control studies related to schizophrenia.

Assessment of association between the dopamine D2 receptor (DRD2) polymorphism and neurodevelopment of children exposed to lead

The mechanism of lead (Pb) neurotoxicity has not been illustrated over the years. People pay more attention to dopaminergic neurotransmission, specifically dopamine receptor-2 (DRD2) Taq IA polymorphism, but no consensus has been reached. A total of 258 three-year-old children in Guiyu (exposed group) and Nanao (reference group), China were examined and their concentrations of blood lead (BPb) were determined. Cognitive and language scores of children were assessed using the Bayley Scales of Infant Development, third edition (BSID-III). Genotyping for the DRD2 polymorphism was carried out using a polymerase chain reaction (PCR) re-sequencing platform. The logistic stepwise regression analysis and stepwise regression analysis was used to explore associations among lead, neurodevelopment of children, and DRD2 Taq IA categories. Median values of Pb in Guiyu was higher than that of the reference group (11.30 ± 5.38 μg/dL vs. 5.77 ± 2.51 μg/dL, P < 0.001). Compared with the reference group, children from e-waste exposed area have lower cognitive scale scores (100 ± 25 vs 120 ± 20, P < 0.001) and lower language scale scores (99.87 ± 7.52 vs 111.39 ± 7.02, P < 0.001). The three kinds of genotype, A1/A1, A1/A2, and A2/A2, had no significant influences on BPb, cognitive scores and language scores (P > 0.05). Exposure of inhabitants, especially children to Pb from informal e-waste recycling activities might have contributed to higher levels of BPb and reduced cognitive and language scores observed in local children, however, the result obtained showed no significant association between DRD2 polymorphism and neurodevelopment of children exposed to lead.

Association between dopamine D4 receptor polymorphism and age related changes in brain glucose metabolism.

Aging is associated with reductions in brain glucose metabolism in some cortical and subcortical regions, but the rate of decrease varies significantly between individuals, likely reflecting genetic and environmental factors and their interactions. Here we test the hypothesis that the variant of the dopamine receptor D4 (DRD4) gene (VNTR in exon 3), which has been associated with novelty seeking and sensitivity to environmental stimuli (negative and positive) including the beneficial effects of physical activity on longevity, influence the effects of aging on the human brain. We used positron emission tomography (PET) and [18F]fluoro-D-glucose (18FDG) to measure brain glucose metabolism (marker of brain function) under baseline conditions (no stimulation) in 82 healthy individuals (age range 22–55 years). We determined their DRD4 genotype and found an interaction with age: individuals who did not carry the 7-repeat allele (7R−, n = 53) had a significant (p<0.0001) negative association between age and relative glucose metabolism (normalized to whole brain glucose metabolism) in frontal (r = −0.52), temporal (r = −0.51) and striatal regions (r = −0.47, p<0.001); such that older individuals had lower metabolism than younger ones. In contrast, for carriers of the 7R allele (7R+ n = 29), these correlations with age were not significant and they only showed a positive association with cerebellar glucose metabolism (r = +0.55; p = 0.002). Regression slopes of regional brain glucose metabolism with age differed significantly between the 7R+ and 7R− groups in cerebellum, inferior temporal cortex and striatum. These results provide evidence that the DRD4 genotype might modulate the associations between regional brain glucose metabolism and age and that the carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism.

Task-dependent interactions between Dopamine D2 receptor polymorphisms and L-DOPA in patients with Parkinson's disease

Variants in genes regulating dopamine transmission affect performance on tasks including working memory and executive function as well as temporal processing and sequence learning. In the current study, we determined whether a dopamine D2 receptor DNA sequence polymorphism interacts with L-DOPA during motor tasks in patients with Parkinson's disease (PD). Forty-five PD patients were genotyped for the DRD2 polymorphism (rs 1076560, G>T). Patients performed an explicit motor sequence learning task and the grooved pegboard test in both ON and OFF L-DOPA states. For motor sequence learning, DRD2 genotype mediated L-DOPA effects such that L-DOPA associated improvements were only observed in the minor T allele carriers (associated with lower D2 receptor availability, t10=−2.71, p=0.022), whereas G homozygotes showed no performance change with L-DOPA. For the grooved pegboard test, performance improved with L-DOPA independent of patients’ DRD2 genotype. Collectively these results demonstrate that common DRD2 allelic differences found in the human population may explain how dopamine differentially contributes to performance across tasks and individuals.

Dopaminergic D4 receptor polymorphism among 24 populations of India: an anthropological insight

Various studies have tried to elucidate the genomics underlying the ethnic diversity of Indian populations. The 48-basepair variable number tandem repeat (VNTR) of the DRD4 gene, besides its clinical importance, has been a subject of interest for understanding human evolutionary history worldwide. In spite of its highly polymorphic nature it has not been much explored by anthropologists, especially in the Indian context. In the present study, an attempt was made to infer the allelic variation of the repeat allele among 24 Indian ethnic groups belonging to different ethnic and linguistic groups along with different geographic affiliations. Only the 2R, 3R, 4R, 5R, 6R, and 7R repeat alleles were found in the studied populations, with 4R being the most frequent followed by 2R. All the other repeat alleles (3R, 5R, 6R, and 7R) occurred at very low frequency. Based on the 4R and 5R frequencies, the study reveals a common genetic substratum of the Indian population as already proposed by earlier studies. Further, the study also highlights the inflow of genes from the north.

PTGDR polymorphisms and susceptibility to asthma: a meta-analysis

The aim of this study was to explore whether prostaglandin D2 receptor (PTGDR) polymorphisms confer susceptibility to asthma. A meta-analysis was conducted on the associations between the PTGDR -549 C/T, -441 C/T, and -197 C/T polymorphisms and asthma using: (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. Three polymorphism haplotypes were constructed in the order -549/-441/-179. Meta-analysis was performed on the haplotype CCC (high transcriptional activity) and of TCT (low transcriptional activity). A total of 13 separate comparative studies in 9 articles involving 7,155 patients with asthma and 7,285 control subjects were included in this meta-analysis. An association between asthma and the PTGDR -549 C/T polymorphism was found by allele contrast (OR = 1.133, 95 % CI = 1.004-1.279, P = 0.043). Ethnicity-specific meta-analysis showed an association between asthma and the PTGDR -549 C allele in Europeans (OR = 1.192, 95 % CI = 1.032-1.377, P = 0.017). Furthermore, stratifying subjects by age indicated an association between the PTGDR -549 C allele and asthma in adults (OR = 1.248, 95 % CI = 1.076-1.447, P = 0.003), but no association in children (OR = 0.933, 95 % CI = 0.756-1.154, P = 0.324). Analyses using the dominant and additive models showed the similar pattern as that observed for the PTGDR -549 C allele, that is, a significant association in Europeans and adults, but not in children. No association was found between asthma and the PTGDR -441 C/T or -197 C/T polymorphisms, and meta-analysis stratified by ethnicity and age also revealed no association between asthma and these polymorphisms. Furthermore, no association was found between asthma and the CCC and TCT haplotypes of PTGDR, and meta-analysis stratified by ethnicity and age revealed no association between asthma and the CCC and TCT PTGDR haplotypes. This meta-analysis demonstrates that the PTGDR -549 C/T polymorphism confers susceptibility to asthma in Europeans and adults. However, no association was found between the PTGDR 441 C/T and -197 C/T polymorphisms or the CCC and TCT haplotypes and asthma susceptibility.

Association between the dopamine D2 receptor (DRD2) polymorphism and the personality traits of healthy Japanese participants

Dopamine neurotransmitter systems have been associated with reward-related and novelty-seeking personality traits. We investigated the possible relationship between the personality traits measured by the Temperament and Character Inventory (TCI) and the TaqI A and -141C Ins/Del polymorphisms in the dopamine D2 receptor gene (DRD2). The sample consisted of 1084 healthy Japanese medical students and medical staff (age=29.0±9.7 years), each of whom completed the TCI. Their genomic DNA was isolated from whole blood and genotyped using the TaqMan allele-specific assay method. The associations between gene polymorphisms and the scores for TCI were statistically analyzed by one-way analysis of covariance (ANCOVA) adjusting age. Males and females were analyzed separately. Epstatis was assesses using two-way ANCOVA between the DRD2 and ANKK1 genes. Men with the Ins/Del genotype of the -141C Ins/Del polymorphism had significantly higher self-directedness scores than those with the Ins/Ins genotype (p=0.021). None of the TCI scores differed among women with regard to the three genotype groups of the -141C Ins/Del polymorphism. The DRD2/ANKK1 Taq1 A polymorphism did not affect any TCI factor for either men or women. An epistatic analysis did not reveal main effects of the two genes with regard to TCI scores, but an ANKK1×DRD2 interaction significantly predicted TCI scores. These findings suggest the possibility that the -141C Ins/Del polymorphism and the DRD2/ANKK1 Taq1 A polymorphism are not strongly linked to personality traits directly, but influences them under the interaction between the DRD2 and ANKK1 genes.

Comparing the Influence of Dopamine D2 Polymorphisms and Plasma Drug Concentrations on the Clinical Response to Risperidone

Although several studies have reported that dopamine D₂ receptor (DRD2) polymorphisms affect the therapeutic efficacy of antipsychotics, other studies have suggested that the plasma drug concentration is related to the clinical response. Currently, there are no definitive data regarding which factor has greater clinical significance. Sixty patients with acute exacerbations of schizophrenia received 6 mg/d of risperidone for 4 weeks. Clinical evaluations using the Brief Psychiatric Rating Scale and the Udvalg for Klinicke Undersøgelser Side Effect Rating Scale were performed before and after administration of risperidone. TaqI A and -141C Ins/Del polymorphisms were determined, and the plasma concentrations of risperidone and 9-hydroxyrisperidone were measured. The TaqI A polymorphism had no effect on therapeutic efficacy, but the -141C Ins/Del polymorphism was associated with an improvement in positive symptoms. In addition, the plasma concentration of the active moiety (risperidone plus 9-hydroxyrisperidone) correlated with the improvement in the total Brief Psychiatric Rating Scale score as well as with positive symptoms. Although there were no associations between DRD2 polymorphisms and psychic adverse effects, the plasma drug concentration was associated with psychic adverse effects. These findings suggest that DRD2 polymorphisms are associated with the therapeutic effects of risperidone as they relate to positive symptoms and that plasma drug concentrations are associated with overall symptoms as well as excitement and cognitive symptoms. Both the genotyping of DRD2 and the monitoring of plasma drug concentrations may be useful for improving clinically dominant symptoms. Further work involving replication in a larger sample is required to support our findings.

Double Dissociation of Dopamine Genes and Timing in Humans

A number of lines of evidence implicate dopamine in timing [Rammsayer, T. H. Neuropharmacological approaches to human timing. In S. Grondin (Ed.), Psychology of time (pp. 295-320). Bingley, UK: Emerald, 2008; Meck, W. H. Neuropharmacology of timing and time perception. Brain Research, Cognitive Brain Research, 3, 227-242, 1996]. Two human genetic polymorphisms are known to modulate dopaminergic activity. DRD2/ANKK1-Taq1a is a D(2) receptor polymorphism associated with decreased D(2) density in the striatum [Jönsson, E. G., Nothen, M. M., Grunhage, F., Farde, L., Nakashima, Y., Propping, P., et al. Polymorphisms in the dopamine D(2) receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Molecular Psychiatry, 4, 290-296, 1999]; COMT Val158Met is a functional polymorphism associated with increased activity of the COMT enzyme such that catabolism of synaptic dopamine is greater in pFC [Meyer-Lindenberg, A., Kohn, P. D., Kolachana, B., Kippenhan, S., McInerney-Leo, A., Nussbaum, R., et al. Midbrain dopamine and prefrontal function in humans: Interaction and modulation by COMT genotype. Nature Neuroscience, 8, 594-596, 2005]. To investigate the role of dopamine in timing, we genotyped 65 individuals for DRD2/ANKK1-Taq1a, COMT Val158Met, and a third polymorphism, BDNF Val66Met, a functional polymorphism affecting the expression of brain-derived neurotrophic factor [Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 112, 257-269, 2003]. Subjects were tested on a temporal discrimination task with sub- and supra-second intervals (500- and 2000-msec standards) as well as a spontaneous motor tempo task. We found a double dissociation for temporal discrimination: the DRD2/ANKK1-Taq1a polymorphism (A1+ allele) was associated with significantly greater variability for the 500-msec duration only, whereas the COMT Val158Met polymorphism (Val/Val homozygotes) was associated with significantly greater variability for the 2000-msec duration only. No differences were detected for the BDNF Vall66Met variant. Additionally, the DRD2/ANKK1-Taq1a polymorphism was associated with a significantly slower preferred motor tempo. These data provide a potential biological basis for the distinctions between sub- and supra-second timing and suggest that BG are integral for the former whereas pFC is implicated in the latter.