DRD2 TaqIA Polymorphism Research Articles

Evaluation of the Relationship Between Dopamine Receptor D2 Gene TaqIA1 Polymorphism and Alcohol Dependence Risk.

Several studies are published, that investigated dopamine receptor 2 (DRD2) gene TaqIA polymorphism as a risk factor for alcohol dependence (AD) with positive and negative associations. To derive a more precise estimation of the relationship, a meta-analysis of case-control studies that examined the association between DRD2 gene Taq1A polymorphism and alcohol dependence was performed. Eligible articles were identified through a search of databases including PubMed, Science Direct, Springer link, and Google Scholar. The association between the DRD2 TaqIA polymorphism and AD susceptibility was conducted using odds ratios (ORs) and 95% confidence intervals (95% CIs) as association measures. A total of 69 studies with 9125 cases and 9123 healthy controls were included in the current meta-analysis. Results of the present analysis showed significant association between DRD2 TaqIA polymorphism and AD risk using five genetic modes (allele contrast model-OR 1.22, 95% CI 1.13-1.32, p < 0.0001; homozygote model-OR 1.35, 95%CI 1.18-1.55; p ≤ 0.0001; dominant model-OR 1.29; 95% CI 1.20-1.39; p < 0.0001; recessive model-OR 1.21; 95% CI 1.08-1.36; p = 0.0006). There was no significant association found in subgroup analysis, TaqIA polymorphism was not significantly associated with AD risk in the Asian population under all genetic models, but in the Caucasian population, TaqIA polymorphism was significantly associated with AD risk. Overall, results support the hypothesis that DRD2 Taq1A polymorphism plays a role in alcohol dependence.

Are COMT Val158Met (rs4680), DRD2 TaqIA (rs1800497), and BDNF Val66Met (rs6265) polymorphisms associated with executive functions performance at rest and during physical exercise?

Executive functions (EFs) encompass a wide array of cognitive processes, which appear to be influenced by genetic variants of the COMT, DRD2/ANKK1, and BDNF polymorphisms. The present study aimed to investigate whether COMT Val158Met (rs4680), DRD2/ANKK1 (rs1800497), and BDNF Val66Met (rs6265) polymorphisms were associated with EFs assessed at rest and during moderate acute physical exercise. Sixty physically active individuals underwent four laboratory visits. First, they filled out the pre-exercise survey, researchers collected their anthropometric data, and then performed a maximal cardiopulmonary exercise test. In the second and third sessions, participants performed EFs test in a randomized order: while the individual was seated on a cycle ergometer without pedaling (i.e., rest condition); and during physical exercise (pedaling for 30 minutes at moderate intensity before starting the EFs test during exercising). On the fourth day, blood samples were drawn. Our results showed that the response time of the COMT Val homozygotes group was significantly shorter than the COMT Met-carrier group [t(39.78) = 2.13, p = .039,d = 0.56] at rest condition. No significant association was found for the other analyses (DRD2/ANKK1 and BDNF). In conclusion, the present study suggests that COMT Val158Met (rs4680) polymorphisms may be associated with EFs at rest condition. However, further studies are needed to validate this association.

The relationship between DRD2 TaqIA polymorphism and tobacco addiction

Objectives: In this study, the relationship between tobacco addiction levels, early smoking, and DRD2 TaqIA polymorphism was investigated. Materials and methods: The present study included 36 smokers and 12 non-smoking voluntary controls. Study groups were established as the non-smoking control group and addicted (less than 1 pack, between 1-2 packs, more than 2 packs per day) groups. Genotypes of the dopamine type-2 receptor (DRD2) gene TaqIA polymorphic region from genomic DNA isolated from oral swab samples were determined by PCR followed by Restriction Fragment Length Polymorphism (RFLP) analysis. Results: Presence of the DRD2 TaqIA homozygous polymorphic genotype in addicted individuals who smoked two or more packs per day and the absence of non-smoker control individuals may indicate that the polymorphic TaqIA allele of the DRD2 gene is associated with smoking. It was found that individuals carrying the polymorphic TaqIA allele in homozygous (~13 years) and heterozygous forms (~16.3 years) had a lower age of starting smoking compared to homozygous wild types (~18.6 years). Mean BMI (body mass index) of the study participants was 24.66 kg/m2 (normal weight), waist/hip ratio 0.82 (no abdominal obesity). Conclusion: The results of our study suggest that the TaqIA variant allele is related to early smoking condition. In addition, it was determined that there was a higher tendency of smoking addiction among children of addicted parents.

DRD2 Taq IA Polymorphism Interacts with Parenting in Predicting Creativity: Evidence of Differential Susceptibility

ABSTRACT This study investigated the interactive effect of Dopamine D2 receptor gene Taq 1A (DRD2 rs1800497) and parental behavior on creativity and examined whether a potential gene–parenting interaction (G × E) would be consistent with one of two models of gene–environment interplay (diathesis-stress vs. differential susceptibility). In a sample of university undergraduates (N = 517), we found evidence of G × E between the DRD2 TaqIA polymorphism and perceived maternal overprotection behavior, but not maternal care, with regard to creativity. Confirmatory model indicates that this interaction effect conformed to the differential susceptibility, rather than diathesis-stress model. Thus, individuals with A1A1 genotype of the DRD2 gene are more creative than A2 carriers when their mothers were less involved in overprotection but less creative under condition of high maternal overprotection. No significant interaction of DRD2 TaqIA polymorphism and paternal behavior was found. Our findings provide initial evidence for the differential susceptibility model in the field of creativity, suggesting DRD2 TaqIA polymorphism may operate as a “plasticity gene.” Further studies need to test these effects.

Association between the DRD2 TaqIA gene polymorphism and Parkinson disease risk: an updated meta-analysis.

Background:DRD2 TaqIA polymorphism may be associated with an increased risk of developing Parkinson disease (PD). However, the individual study's results are still inconsistent.Methods:A meta-analysis of 4232 cases and 4774 controls from 14 separate studies were performed to explore the possible relationship between the DRD2 TaqIA gene polymorphism and PD. Pooled odds ratios (ORs) for the association and the corresponding 95% confidence intervals (CIs) were evaluated by a fixed-effect model.Results:The pooled results revealed a significant association between DRD2 gene TaqIA polymorphism under recessive genetic model (OR: 0.91, 95% CI:0.83,0.99, P = .031) and additive genetic models (OR:0.93,95%CI:0.87,0.99, P = .032), but not associated with PD susceptibility under other genetic models in the whole population. Moreover, subgroups based on ethnicity and genotyping methods showed this association in the Caucasian subgroup under recessive genetic model (OR: 0.85, 95% CI:0.76,0.95, P = .003) and additive genetic models (OR:0.87,95%CI:0.79,0.96, P = .004) were existed. Besides, no significant association was detected under 6 genetic models in the Asian populations and PCR-RFLP subgroup.Conclusions:The current meta-analysis suggested that a significant association between DRD2 TaqIA polymorphism and PD under the recessive genetic mode, and additive genetic models, especially in Caucasians.

Evaluation of association of DRD2 TaqIA and -141C InsDel polymorphisms with food intake and anthropometric data in children at the first stages of development.

The reward sensation after food intake may be different between individuals and variants in genes related to the dopaminergic system may indicate a different response in people exposed to the same environmental factors. This study investigated the association of TaqIA (rs1800497) and -141C InsDel (rs1799732) variants in DRD2/ANKK1 gene with food intake and adiposity parameters in a cohort of children. The sample consisted of 270 children followed until 7 to 8 years old. DNA was extracted from blood and polymorphisms were detected by PCR-RFLP analysis. Food intake and nutritional status were compared among individuals with different SNP genotypes. Children carrying the A1 allele (TaqIA) had higher energy of lipid dense foods (LDF) when compared with A2/A2 homozygous children at 7 to 8 years old (GLM p=0.004; Mann Whitney p=0.005). No association was detected with -141C Ins/Del polymorphism. To our knowledge, this is the first association study of the DRD2 TaqIA and -141C Ins/Del polymorphism with food intake and anthropometric parameters in children. DRD2 TaqIA polymorphism has been associated with a reduction in D2 dopamine receptor availability. Therefore, the differences observed in LDF intake in our sample may occur as an effort to compensate the hypodopaminergic functioning.

Behavioral and Neural Manifestations of Reward Memory in Carriers of Low-Expressing versus High-Expressing Genetic Variants of the Dopamine D2 Receptor.

Dopamine is critically important in the neural manifestation of motivated behavior, and alterations in the human dopaminergic system have been implicated in the etiology of motivation-related psychiatric disorders, most prominently addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2) availability in the striatum, and the DRD2 TaqIA (rs1800497) and C957T (rs6277) genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence. Here, we investigated the hypothesis that the variants of these polymorphisms would show increased reward-related memory formation, which has previously been shown to jointly engage the mesolimbic dopaminergic system and the hippocampus, as a potential intermediate phenotype for addiction memory. To this end, we performed functional magnetic resonance imaging (fMRI) in 62 young, healthy individuals genotyped for DRD2 TaqIA and C957T variants. Participants performed an incentive delay task, followed by a recognition memory task 24 h later. We observed effects of both genotypes on the overall recognition performance with carriers of low-expressing variants, namely TaqIA A1 carriers and C957T C homozygotes, showing better performance than the other genotype groups. In addition to the better memory performance, C957T C homozygotes also exhibited a response bias for cues predicting monetary reward. At the neural level, the C957T polymorphism was associated with a genotype-related modulation of right hippocampal and striatal fMRI responses predictive of subsequent recognition confidence for reward-predicting items. Our results indicate that genetic variations associated with DRD2 expression affect explicit memory, specifically for rewarded stimuli. We suggest that the relatively better memory for rewarded stimuli in carriers of low-expressing DRD2 variants may reflect an intermediate phenotype of addiction memory.

Associations Between Dopamine D2 Receptor (DRD2) Gene, Maternal Positive Parenting and Trajectories of Depressive Symptoms from Early to Mid-Adolescence.

Using data from the Longitudinal Study of Chinese Children and Adolescents (LSCCA), this study is the first to examine the roles of the dopamine D2 receptor (DRD2) gene polymorphisms (i.e., TaqIA and A241G) and maternal positive parenting at ages 10 and 11years in the trajectories of depressive symptoms from early to mid-adolescence (ages 11 to 16years). In a sample of 1090 Chinese adolescents (50% girls), three trajectories of depressive symptoms were identified: (i) low-stable (36.1%), (ii) moderate-increasing (44.5%), and (iii) high-increasing (19.4%). A241G AA homozygotes and youth exposed to lower levels of maternal positive parenting were both at increased odds to follow the high-increasing vs. low-stable trajectory. Moreover, the A241G polymorphism interacted with maternal positive parenting to distinguish the moderate-increasing trajectory from the high-increasing and the low-stable trajectories. For A241G G-allele carriers, but not AA homozygotes, exposure to high quality of maternal parenting decreased the odds to follow the high-increasing vs. moderate-increasing trajectory of depressive symptoms. For AA homozygotes, but not G-allele carriers, high quality of maternal parenting increased the odds to follow the low-stable vs. moderate-increasing trajectory. The DRD2 TaqIA polymorphism had neither a direct nor an interactive effect with maternal positive parenting on trajectory membership. The current findings highlight the importance of investigating gene-by-environment interactions (G×E) in trajectories of depressive symptoms over adolescence, and support a developmental versus static nature of G×E effects.

Postoperative nausea and vomiting: The role of the dopamine D2 receptor TaqIA polymorphism.

The risk of developing postoperative nausea and vomiting (PONV), apart from conventional risk factors, probably includes a genetic background. We examined the association of the DRD2 TaqIA polymorphism with PONV in a high-risk cohort of patients. A prospective, double-blind observational trial. Single-centre primary care in Western Germany. A total of 306 patients undergoing elective strabismus surgery under anaesthesia with etomidate/alfentanil/mivacurium (induction) and sevoflurane in air (maintenance). Nausea as well as retching/vomiting was recorded for 24 h postoperatively. The DRD2 TaqIA polymorphism (rs1800497) was genotyped using a Taqman assay and the relationship between DRD2 TaqIA polymorphism and PONV was examined by univariate and multivariate analysis. Regarding known risk factors for developing PONV, no patient with the A1A1 genotype (n = 15) had a history of PONV, while A1A2 carriers (n = 115) and A2A2 carriers (n = 176) had a history of PONV in 22.6 and 10.8% of patients, respectively (P = 0.005). Overall, the incidence of nausea was 40.1% and the incidence of vomiting/retching was 32.7%. Univariate analysis showed that postoperative nausea was not associated with TaqIA genotypes, but the incidence of retching/vomiting in A1A2 and A2A2 genotypes was more than 34% compared with zero in A1A1 genotypes (P = 0.022). Age, sex, smoking status and a history of PONV were independent predictors for nausea as well as for retching/vomiting, as expected, while DRD2 TaqIA polymorphism showed no independent significant impact. In a white cohort, the TaqIA A2 allele is significantly associated with a history of PONV, which may explain the increased incidence of PONV but has no further independent influence. German registry of clinical trials identifier: DRKS00005681.

Relation of addiction with dopamine 2 receptor (DRD2) TaqIA polymorphism in heroin addicts

Objective: To understand the etiologic reasons of heroin addiction will make an important contribution to the prevention and treatment of this disease. It is thought that DRD2 TaqIA gene polymorphism affects the reward system by causing hyperdopaminergic activity and thereby might also lead to the development of substance addiction. The purpose of this study is to examine the possible relation between TaqIA polymorphism and heroin addiction. Methods: One hundred patients, who applied to Ankara Numune Hospital Alcohol and Substance Treatment and Training Centre for treatment and were diagnosed with heroin addiction as a result of the clinical evaluation that was conducted in accordance with DSM-IV were included in this study. One hundred healthy volunteers, who accepted to participate in the study as the control group and were matched with the patient group in terms of age and gender, were involved. Results: There was no statistically significant difference between the patient and control groups in terms of A1 allele carrier. As a result of the evaluation that was performed by dividing the patient group into two groups according to A1 allele carrier, no statistically significant relation was determined between the substance-use features and A1 allele. Conclusion: DRD2 TaqIA polymorphism, which is known to be associated with reward pathways, cannot be a genetic factor that is effective on the development of heroin addiction alone and it is required to consider different genes and gene-gene interactions in broader sample groups in order to determine the genetic factors causing the addiction.

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.

Interaction of DRD2TaqI, COMT, and ALDH2 genes associated with bipolar II disorder comorbid with anxiety disorders in Han Chinese in Taiwan

It is hypothesized that dopaminergic genes-dopamine type-2 receptor (DRD2), aldehyde dehydrogenase 2 (ALDH2), and catechol-O-methyltransferase (COMT)-are associated with bipolar disorder (BP) and anxiety disorder (AD). Bipolar II (BP-II) is reported to be highly comorbid with AD. We examined whether interactions among these three genes are susceptibility factors in BP-II with AD (BP-II(+AD)) and without AD (BP-II(-AD)). In this study, we hypothesize that the interaction of the dopaminergic genes between BP-II(+AD) and BP-II(-AD) is significant different. We recruited 1260 participants: 495 with BP-II(-AD), 170 with BP-II(+AD), and 595 healthy controls without BP-II or AD. Genotyping was done using polymerase chain reactions plus restriction fragment length polymorphism analysis. Genotypic frequencies of the DRD2TaqIA, COMT, and ALDH2 polymorphisms between the two BP-II groups were nonsignificant. In logistic regression, the ALDH2 and DRD2TaqIA genes showed a main effect that was protective against BP-II(-AD) (odds ratio [OR] = 0.497, p = 0.010, and OR = 0.415, p = 0.017, respectively). The interaction of DRD2TaqIA A1/A1 and ALDH2*1/*1 had a significant risk effect on the BP-II(-AD) group (OR = 7.177, p < 0.001). However, the interaction of DRD2TaqIA A1/A1, ALDH2*1/*1, and COMTMet/Met&Val/Met become a weak protective factor against BP-II(-AD) (OR = 0.205, p = 0.047). All of the significant results described above are found only in BP-II(-AD). This study supports the hypothesis the interaction of the dopaminergic genes between BP-II(+AD) and BP-II(-AD) is significant different,, and provides additional evidence that the DRD2TaqIA A1/A1, ALDH2*1/*1 and COMT genes interact in BP-II(-AD) but not in BP-II(+AD).

Role ofDRD2andALDH2genes in bipolar II disorder with and without comorbid anxiety disorder

The presence of comorbid anxiety disorders (AD) and bipolar II disorders (BP-II) compounds disability complicates treatment, worsens prognosis, and has been understudied. The genes involved in metabolizing dopamine and encoding dopamine receptors, such as aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor (DRD2) genes, may be important to the pathogenesis of BP-II comorbid with AD. We aimed to clarify ALDH2 and DRD2 genes for predisposition to BP-II comorbid with and without AD. The sample consisted of 335 subjects BP-II without AD, 127 subjects BP-II with AD and 348 healthy subjects as normal control. The genotypes of the ALDH2 and DRD2 Taq-IA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Logistic regression analysis showed a statistically significant association between DRD2 Taq-I A1/A2 genotype and BP-II with AD (OR=2.231, P=0.021). Moreover, a significant interaction of the DRD2 Taq-I A1/A1 and the ALDH2*1*1 genotypes in BP-II without AD was revealed (OR=5.623, P=0.001) compared with normal control. Our findings support the hypothesis that a unique genetic distinction between BP-II with and without AD, and suggest a novel association between DRD2 Taq-I A1/A2 genotype and BP-II with AD. Our study also provides further evidence that the ALDH2 and DRD2 genes interact in BP-II, particularly BP-II without AD.

Gender-specific association of the SLC6A4 and DRD2 gene variants in bipolar disorder

Findings on the association between the risk for developing bipolar disorder and the functions of the serotonin transporter-linked polymorphic region gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) variants are contradictory. One explanation for this is that a gender difference may exist for genetic contributions. We compared the gender-related main effects and the gene-to-gene interaction between serotonin transporter gene (SLC6A4) and DRD2 in adult male and female patients with bipolar I (BP-I) and bipolar II (BP-II) disorder. Patients with BP-I (n = 400) and BP-II (n = 493), and healthy controls (n = 442) were recruited from Taiwan's Han Chinese population. The genotypes of the 5-HTTLPR and DRD2 Taq-IA polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Logistic regression analysis showed a significant gender-specific association of the DRD2 A1/A1 and the 5-HTTLPR S/S, S/LG , and LG/LG (S+) (p = 0.01) genotypes in men with BP-I (p = 0.002 and 0.01, respectively) and BP-II (p = 0.001 and 0.007, respectively), but not in women. A significant interaction for the DRD2 A1/A1 and 5-HTTLPR S+ polymorphisms was also found only in men with BP-I and BP-II (p = 0.003 and 0.001, respectively). We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants for the risk of BP-I and of BP-II. We also found gender-specific interaction between 5-HTTLPR and DRD2 Taq-IA polymorphisms in patients with bipolar disorder.

Association of DRD2 TaqIA and D&amp;#946;H -1021C&amp;#62;T Gene Polymorphisms with Smoking Initiation and their Interaction with Serotonergic System Gene Polymorphisms

The dopaminergic system has an important role in the rewarding properties of nicotine. Gene polymorphisms of DRD2 and DβH that regulate dopamine neurotransmission or metabolism could influence smoking behavior. Additionally, the ability of a 5-HT2CR agonist to block mesolimbic dopamine activation produced by nicotine at the level of ventral tegmental area, suggests a possible interaction between dopaminergic and serotonergic systems in smoking initiation. In the present study, DRD2 TaqIA and DβH -1021C>T polymorphisms and their interactions with 5-HT2CR - 759C>T and -697G>C and 5HTTLPR S/L polymorphisms of serotonergic system were analyzed in 166 smoking initiators (SI) and 244 non-initiators (NI) of Greek origin, using PCR-RFLP method. No differences were found in genotype distributions of DRDR2 TaqIA and DβH -1021C>T polymorphisms between SI and NI. Also, we found no interaction of DRD2 TaqIA and DβH -1021C>T with smoking initiation. When DRD2 TaqIA polymorphism was combined with 5- HT2CR -759C>T and -697G>C polymorphisms, the interaction of DRD2 TaqIA1 and 5-HT2CR -759T alleles was associated with smoking initiation in a model adjusted for age, sex, BMI and type 2 diabetes mellitus (OR=0.70, p=0.022) but did not improve the model that includes 5-HT2CR -759C>T polymorphism alone (OR=0.52, p=0.028). DRDR2 TaqIA and DβH -1021C>T polymorphisms were not associated with smoking initiation. The lower risk for smoking initiation conferred by the combination of DRD2 TaqIA1 and 5-HT2CR -759T variant alleles, indicates the presence of dopaminergic/serotonergic system interaction in smoking behavior; however, this interaction does not substantially improve the predictive value of 5-HT2CR -759T allele alone on smoking initiation risk. To the best of our knowledge, this is the first study of gene polymorphisms in multiple dopaminergic components in relation to smoking initiation, and of the interaction of gene polymorphisms of dopaminergic and serotonergic components in relation to this smoking phenotype in a large sample free of alcohol or drug dependencies. Keywords: Dopamine, DβH, DRD2, genes, serotonin, smoking, 5-HT2CR, 5HTTLPR.

Motivational salience and genetic variability of dopamine D2 receptor expression interact in the modulation of interference processing

Dopamine has been implicated in the fine-tuning of complex cognitive and motor function and also in the anticipation of future rewards. This dual function of dopamine suggests that dopamine might be involved in the generation of active motivated behavior. The DRD2 TaqIA polymorphism of the dopamine D2 receptor gene (rs1800497) has previously been suggested to affect striatal function with carriers of the less common A1 allele exhibiting reduced striatal D2 receptor density and increased risk for addiction. Here we aimed to investigate the influences of DRD2 TaqIA genotype on the modulation of interference processing by reward and punishment. Forty-six young, healthy volunteers participated in a behavioral experiment, and 32 underwent functional magnetic resonance imaging (fMRI). Participants performed a flanker task with a motivation manipulation (monetary reward, monetary loss, neither, or both). Reaction times (RTs) were shorter in motivated flanker trials, irrespective of congruency. In the fMRI experiment motivation was associated with reduced prefrontal activation during incongruent vs. congruent flanker trials, possibly reflecting increased processing efficiency. DRD2 TaqIA genotype did not affect overall RTs, but interacted with motivation on the congruency-related RT differences, with A1 carriers showing smaller interference effects to reward alone and A2 homozygotes exhibiting a specific interference reduction during combined reward (REW) and punishment trials (PUN). In fMRI, anterior cingulate activity showed a similar pattern of genotype-related modulation. Additionally, A1 carriers showed increased anterior insula activation relative to A2 homozygotes. Our results point to a role for genetic variations of the dopaminergic system in individual differences of cognition-motivation interaction.

Association study of DRD2 and MAOA genes with subtyped alcoholism comorbid with bipolar disorder in Han Chinese

Several studies have hypothesized that genes involved in the dopamine system, including dopamine type-2 receptor (DRD2)-related TaqIA polymorphism and monoamine oxidase-A upstream variable number tandem repeat (uVNTR), may be associated with alcoholism. But their results were contradictory because of alcoholism's heterogeneity. Therefore, we examined whether the DRD2TaqIA and MAOA-uVNTR gene polymorphisms are susceptibility factors for alcoholism comorbid with bipolar disorder (ALC+BP) in Han Chinese in Taiwan. We recruited 101 Han Chinese men with comorbid alcoholism and bipolar disorder, and 328 healthy male controls from the community. Genotyping was done using PCR-RFLP. There were no significant differences in the genotypic frequencies of the DRD2TaqIA or the MAOA-uVNTR polymorphisms between the 2 groups. The MAOA-uVNTR 3-repeat had a significant protective effect on the ALC+BP (odds ratio=0.432, p=0.035) but not on the healthy controls. However, the interaction between the MAOA-uVNTR 3-repeat and DRD2 A1/A2 was a risk factor in the ALC+BP (odds ratio=3.451, p=0.018). We indicated the impact of the association between MAOA-uVNTR 3-repeat and DRD2 A1/A2 with ALC+BP.

POSTER SESSION 2: MARKERS, PSYCHIATRY AND TREATMENT * MARKERS * P49 * BIOMARKERS DEMONSTRATE INCREASED CONSUMPTION BUT NOT ABUSE OF ETHANOL IN ESSENTIAL TREMOR

Dopaminergic neurotransmissions play indispensible roles in modulation ofaddictive behaviours through personality and stress response. This study aimsat exploring the relationships among personality traits, salivary cortisol andalcohol craving in alcohol-dependent subjects, and the associations betweenthese parameters and gene polymorphisms involved. Alcohol-dependent subjects(n = 156) were recruited during a 5-day detoxification treatment.Neuroticism (N), extraversion (E) and conscientiousness (C) were measuredby NEO PI-R; harm avoidance (HA), reward dependence (RD), noveltyseeking (NS), persistence (P) and self-directedness (SD) were measured byTridimensional Character Inventory. Alcohol craving level was measured byAlcohol Urge Questionnaire in the morning of day 3–day 5, and a salivasample was collected subsequently for cortisol measurement. Genotyping wasdone on by PCR-RFLP. Results showed that alcohol craving correlated withsalivary cortisol level in female subjects (Spearman’s ρ = 0.430, P = 0.022)but not in male subjects. Alcohol craving is significantly (P < 0.05) correlatedwith N, C, NS and RD scores for male subjects but with E, C, NS and Pscores for female subjects. Significant correlation between alcohol cravingand these personality traits was only observed in DRD2 TaqIA A1-allele carriers,whose craving level was negatively correlated with RD scores (adjustedr2 = 0.191, P < 0.001). Structural equation modeling revealed the effect ofDRD2 TaqIA on alcohol craving is mediated through RD trait. The currentfindings suggest that correlations between alcohol craving, salivary cortisollevel and certain addiction-related personality traits are gender-specific.DRD2 TaqIA polymorphisms may be associated with alcohol craving levelthrough mediation of RD trait: alcohol-dependent A1-carrying patients withmore prominent RD trait may benefit from a detoxification treatment environmentin which alcohol craving level is low.

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

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

DRD2 and DRD4 in relation to regular alcohol and cannabis use among adolescents: Does parenting modify the impact of genetic vulnerability? The TRAILS study

AimsThe aims of the present study were to determine the direct effect of DRD2 and DRD4, as well as their interaction with parenting (i.e. rejection, overprotection and emotional warmth), on the development of regular alcohol and cannabis use in 1192 Dutch adolescents from the general population. MethodsInformation was obtained by self-report questionnaires. Perceived rejection, overprotection and emotional warmth were assessed at age 10–12. Regular alcohol and cannabis use were determined at age 15–18 and defined as the consumption of alcohol on 10 or more occasions in the past four weeks, and the use of cannabis on 4 or more occasions in the past four weeks. Models were adjusted for age, sex, parental alcohol or cannabis use, and externalizing behavior. ResultsCarrying the A1 allele of the DRD2 TaqIA polymorphism, or the 7 repeat DRD4, was not directly related to regular alcohol or cannabis use. In addition, adolescent carriers of these genetic risk markers were not more susceptible to the influence of less optimal parenting. Main effects for parenting indicated that overprotection increased the risk of regular alcohol use, whereas the risk of cannabis use was enhanced by parental rejection and buffered by emotional warmth. ConclusionsOur findings do not support an association between DRD2/DRD4 and regular alcohol and cannabis use in adolescents. Given the substance-specific influences of rejection, overprotection and emotional warmth, these parenting factors might be promising candidates for prevention work.