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PubMed2006

The DRD2 TaqI-B polymorphism and its relationship to smoking abstinence and withdrawal symptoms.

The dopamine receptor D2 (DRD2) gene has polymorphisms that have been linked to regulation of the dopamine system and to an increased prevalence of smoking. The present study examined the relationship of the DRD2 TaqI-A and -B polymorphisms with short-term clinical outcome (abstinence and withdrawal symptoms), collected from daily (14 pre-quit and 42 post-quit) diary data among smokers (n=116) treated with the nicotine patch plus either venlafaxine or placebo. The results showed that B1/B1 or B1/B2 smokers were slightly less likely to be abstinent on a given day than those homozygous for the TaqI-B2 allele. Significant DRD2 TaqI-B x time interactions were found for several of the withdrawal scales, indicating that those smokers with the B1/B1 or B1/B2 genotypes tended to report more symptoms over time compared to those with the B2/B2 genotype. No interactions or main effects were found for the DRD2 TaqI-A polymorphism. The findings demonstrate that smokers homozygous for the TaqI-B2 allele experience progressive improvement in self-reported withdrawal symptoms while smokers with the TaqI-B1 allele showing little change.

Administration, Cutaneous↗

PubMed2003

Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor.

Although changes in nucleotide sequence affecting the composition and the structure of proteins are well known, functional changes resulting from nucleotide substitutions cannot always be inferred from simple analysis of DNA sequence. Because a strong synonymous codon usage bias in the human DRD2 gene, suggesting selection on synonymous positions, was revealed by the relative independence of the G+C content of the third codon positions from the isochoric G+C frequencies, we chose to investigate functional effects of the six known naturally occurring synonymous changes (C132T, G423A, T765C, C939T, C957T, and G1101A) in the human DRD2. We report here that some synonymous mutations in the human DRD2 have functional effects and suggest a novel genetic mechanism. 957T, rather than being 'silent', altered the predicted mRNA folding, led to a decrease in mRNA stability and translation, and dramatically changed dopamine-induced up-regulation of DRD2 expression. 1101A did not show an effect by itself but annulled the above effects of 957T in the compound clone 957T/1101A, demonstrating that combinations of synonymous mutations can have functional consequences drastically different from those of each isolated mutation. C957T was found to be in linkage disequilibrium in a European-American population with the -141C Ins/Del and TaqI 'A' variants, which have been reported to be associated with schizophrenia and alcoholism, respectively. These results call into question some assumptions made about synonymous variation in molecular population genetics and gene-mapping studies of diseases with complex inheritance, and indicate that synonymous variation can have effects of potential pathophysiological and pharmacogenetic importance.

Dopamine↗

PubMed2006

Haplotype spanning TTC12 and ANKK1, flanked by the DRD2 and NCAM1 loci, is strongly associated to nicotine dependence in two distinct American populations.

Nicotine dependence (ND) is a moderately heritable trait. We ascertained a set of 1615 subjects in 632 families [319 African-American (AA) and 313 European-American (EA)] based on affected sibling pairs with cocaine or opioid dependence. Subjects were interviewed with the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). Previously, we identified a modest linkage peak (LOD score =1.97) for ND in the EA part of the sample on chromosome 11q23, a region that includes the NCAM1-TTC12-ANKK1-DRD2 gene cluster. DRD2 and NCAM1 are functional candidate genes for substance dependence; the TTC12 and ANKK1 loci are not well characterized. We genotyped a set of 43 single nucleotide polymorphisms (SNPs) spanning this region, and performed family-based association and haplotype analysis. There was relatively weak evidence for association of the flanking DRD2 and NCAM1 markers to ND, but very strong evidence of association of multiple SNPs at TTC12 and ANKK1 in both populations (minimal P=0.0007 in AAs and minimal P=0.00009 in EAs), and in the pooled sample, as well as strong evidence for highly significant association of a single haplotype spanning TTC12 and ANKK1 to ND in the pooled sample (P=0.0000001). We conclude that a risk locus for ND, important both in AAs and EAs, maps to a region that spans TTC12 and ANKK1. Functional studies of these loci are warranted. These results provide additional information useful in evaluating the many earlier discrepant findings regarding association of DRD2 with substance dependence.

Adult↗

PubMed2002

Dopamine DRD2 Taq I polymorphism associates with caudate nucleus volume and cognitive performance in memory impaired subjects.

We studied the relationship among dopamine receptor D2 (DRD2) Taq I genetic polymorphism, caudate nucleus volumetry as measured using MRI and neuropsychological functions in 49 memory impaired older people. Compared with DRD2 A1 carriers, subjects homozygous for the DRD2 A2 allele performed poorer in a measure of general cognitive functioning (MMSE) and in long term verbal memory, and presented reduced left caudate nucleus volumes. Caudate nucleus atrophy correlated with cognitive measures influenced by the genetic polymorphism and with visual memory performance. Our findings suggest that among the aged with cognitive impairments, the homozygous status for the A2 allele of the DRD2 Taq I polymorphism is associated with diminished cognitive performance and increased atrophy in the striatum.

Age Factors↗

PubMed2001

Influence of the dopamine D2 receptor (DRD2) exon 8 genotype on efficacy of tiapride and clinical outcome of alcohol withdrawal.

We tested the hypothesis that allelic variants of the human dopamine D2 receptor E8 genotype are associated with (i) dopamine D2 antagonist tiapride dose in treatment of alcohol withdrawal (n = 50) and (ii) with anxiety and depression in patients during alcoholism detoxification therapy (admission n = 87; discharge n = 50). DRD2 E8 A/A genotype was associated with increased dose of tiapride during a 9-day detoxification therapy and with increased anxiety and depression scores on admission and 2 weeks later. The findings suggest a pharmacogenetic influence of DRD2 E8 genotype on tiapride efficacy in alcohol withdrawal. In an earlier report, DRD2 E8 A/A genotype was associated with reduced responsiveness to the dopamine D2 agonist apomorphine; however, it is not clear whether both findings share the same biological basis. Earlier findings concerning association of DRD2 E8 A/A with increased anxiety and depression are replicated for the first time.

Adult↗

PubMed2004

ADH1B1, ADH1C2, DRD2 (-141C Ins), and 5-HTTLPR are associated with alcoholism in Mexican American men living in Los Angeles.

BACKGROUND: The aim of the present study was to use a candidate gene approach to identify the genetic risk factors for alcoholism in Mexican Americans residing in the Los Angeles area. The genes selected include alcohol metabolizing genes and neurotransmitter genes, which have been shown in the literature to be associated with alcoholism in other ethnic groups. METHODS: Thirteen allelic variants from seven genes were evaluated for their role in alcoholism using alcoholic (n = 200) and nonalcoholic (n = 251) Mexican Americans. Those polymorphic sites include alcohol dehydrogenase (ADH1B, ADH1C), aldehyde dehydrogenase (ALDH2), cytochrome P-450 2E1 (CYP2E1) TaqI, DraI, RsaI, dopamine D2 receptor (DRD2) TaqI A, B, intron 6, exon 7, -141C Ins/Del, serotonin transporter (5-HTTLPR), and GABAA receptor beta3 subunit (GABRbeta3). RESULTS: The results demonstrate that Mexican Americans have extremely low allele frequency for both ALDH2*2 and ADH1B*2 and a relatively high frequency of ADH1C*2 and CYP2E1 c2 alleles. ADH1B*1, ADH1C*2, DRD2 (-141C Ins), and 5-HTTLPR were associated with alcoholism in Mexican Americans (p < 0.05). DRD2 Ins was associated with alcoholism in those alcoholics who carried the ADH1B*2 or ADH1C*1 protective alleles (p = 0.032 in genotype level and p = 0.015 in allele level). DRD2 TaqI A and B alleles were associated with early age of onset for drinking (p = 0.016 for TaqI A1 and p = 0.049 for TaqI B1 allele). CONCLUSIONS: Together, the data reveal unique genetic patterns in Mexican Americans that may be in part responsible for the heightened risk for alcoholism and alcohol-associated health problems in this population.

Adult↗

PubMed2005

Polymorphisms of the dopamine receptor gene DRD2 and colorectal cancer risk.

Sporadic colorectal cancer is considered a multifactorial disease in which multiple exposures interact with the individual genetic background resulting in risk modulation. Recent experimental data suggest a role of dopamine and dopamine receptors in the control of proliferation of the cells of colon and gastrointestinal tract. To investigate whether polymorphisms within dopamine receptors genes could have a role in modulating the risk of sporadic colorectal cancer, we did a case-control association study and genotyped 370 cases and 327 controls for seven single-nucleotide polymorphisms (SNP) of DRD2 (-141Cdel, 957T>C, TaqIB, TaqIA, 1412A>G, S311C, and 3208G>T) by a microarray-based technique. Three SNPs within DRD2 were associated with colorectal cancer, with a maximum odds ratio of 2.28 (95% confidence interval, 1.38-3.76) for carriers of the functional SNP -141Cdel. The haplotype which includes -141Cdel, together with the variants 957C and 1412G, shows an odds ratio of 2.86 (95% confidence interval, 1.58-5.18), as compared with the most frequent haplotype. The SNPs within DRD2 associated with colorectal cancer are known to be related to reduced levels of D2 dopamine receptor. Thus, our data point to a possible role of dopamine receptor DRD2 in modulating the risk of colorectal cancer. Future studies on dopamine receptor-mediated signal transduction may provide new insight into the mechanisms of colorectal cancer and suggest new therapeutic strategies.

Adult↗

PubMed2007

Examining impulsivity as an endophenotype using a behavioral approach: a DRD2 TaqI A and DRD4 48-bp VNTR association study.

BACKGROUND: Research on the genetic basis for impulsivity has revealed an array of ambiguous findings. This may be a result of limitations to self-report assessments of impulsivity. Behavioral measures that assess more narrowly defined aspects of impulsivity may clarify genetic influences. This study examined the relationship between possession of the DRD2 TaqI A and DRD4 48 bp VNTR genetic polymorphisms and performance on a behavioral measure of impulsivity, the delay discounting task (DDT), and three traditional self-report measures. METHODS: 195 individuals (42% male) were recruited from a university campus and were assessed in small group sessions using personal computers. Genotyping was conducted using previously established protocols. For the DRD2 TaqI A locus, individuals were designated as possessing at least one copy of the A1 allele (A1+) or not (A1-), and for the DRD4 48-bp VNTR locus, individuals were designated as having at least one long allele (7 repeats or longer, L+) or not (L-). Principal analyses used multiple univariate factorial 2 (A1+/A1-) x 2 (L+/L-) analyses of variance. RESULTS: A significant main effect of A1+ status on DDT performance was evident (p = .006) as well as a significant interaction effect (p = .006) between both genes. No other significant effects were evident on the self-report measures, with the exception of a trend toward an interaction effect on the Sensation Seeking Scale. Exploratory analyses suggested that the significant effects were not a function of population stratification or gender. DISCUSSION: These data suggest that the DRD2 TaqI A and DRD4 VNTR polymorphisms influence impulsivity as measured with a delay discounting task. Specifically, these findings suggest that an interaction between the functional effects of the two unlinked genotypes results in significant difference in the balance of mesolimbic dopaminergic activation relative to frontal-parietal activation. However, these findings are also the first in this area and must be replicated. CONCLUSION: These findings suggest a meaningful interaction between the DRD2 TaqI A and DRD4 VNTR polymorphisms in the expression of impulsivity and provide initial support for the utility of using behavioral measures for clarifying genetic influences on impulsivity.

Journal Article↗

PubMed2007

An association study of DRD2 and COMT polymorphisms with novelty seeking and harm avoidance scores, in two independent samples of depressed patients.

BACKGROUND: It was recently reported that an interaction of the dopamine D2 receptor (DRD2) and catechol-O-methyltransferase (COMT) influences the behavioural approach system--as measured using Carver and White's Behavioural Inhibition and Behavioural Approach System (BIS/BAS) scales--in a sample of healthy German subjects. The Temperament and Character Inventory (TCI), in particular the novelty seeking (NS) and harm avoidance (HA) scales, correlates moderately with the BIS/BAS measure. This study aimed to examine support for an association of DRD2 and COMT with behavioural activation, using the TCI within two independent samples of depressed outpatients (for both samples n = 146). METHODS: Two clinical samples of depressed patients were ascertained to assess the efficacy of two different pharmacotherapy and psychotherapy treatments. Analysis of variance (ANOVA) was used to analyse NS and HA scale and subscale scores with respect to gene loci within each clinical sample. Analysis of covariance were undertaken to examine the association of age and gender with NS and HA scores. An association of age group or gender with gene loci were explored using chi-squared tests, in each sample. RESULTS: No significant effect of DRD2 or COMT, either independently or as an interaction, on NS or HA scores was observed, within either sample. Whilst age was significantly negatively associated with NS scores, including age in the two- and three-way interactions did not affect the significance of the association of personality with gene loci. CONCLUSION: This study suggests that the COMT-DRD2 Equilibrium Model of Positive Emotionality recently proposed by Reuter and his colleagues is not applicable amongst currently depressed individuals, whose behavioural approach and inhibition tendencies have been assessed using the TCI.

Journal Article↗

PubMed2004

Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele.

BACKGROUND: Hyperprolactinaemia induced by D(2) dopamine receptor antagonist antipsychotic medication can result in significant health problems. AIMS: To examine the role of DRD2 polymorphism on prolactin levels in patients treated with antipsychotic medication. METHOD: Antipsychotic drugs with different degrees of D(2) receptor binding were given to 144 patients with schizophrenia. Serum prolactin levels were obtained and Taq1A DRD2 alleles were determined. RESULTS: Prolactin levels increased across medication groups reflecting increasingly tight D(2) receptor binding (clozapine, olanzapine, typical antipsychotics and risperidone). In the combined medication group, patients with the DRD2(*)A1allele had 40% higher prolactin levels than patients without this allele. In patients treated with clozapine (the loosest D(2) receptor binding agent), patients with the DRD2(*)A1allele had prolactin levels twice those of patients without this allele. CONCLUSIONS: Patients with the DRD2A1 allele receiving antipsychotic medications had higher prolactin levels and were overrepresented among those with hyperprolactinaemia, suggesting greater functional D(2) receptor binding in this group.

Adolescent↗

PubMed1997

Evaluation of four candidate genes encoding proteins of the dopamine pathway in familial and sporadic Parkinson's disease: evidence for association of a DRD2 allele.

We assessed the role of four candidate genes encoding proteins involved in dopaminergic transmission, the dopamine transporter (DAT), the dopamine receptor D2 (DRD2), and the main catabolic enzymes of dopamine, monoamine oxidase A (MAOA) and B (MAOB), through allelic association studies in a population of familial and sporadic Parkinson's disease (PD). Using intronic polymorphisms of the four candidate genes, we studied the allelic distributions of the polymorphic markers in 18 affected members, one patient was chosen randomly from each PD family; 60 sporadic PD and 60 healthy unrelated control subjects were matched for sex and for country of origin. All subjects were white. To complete the study of the DRD2, we subsequently tested 40 additional sporadic PD and 40 control patients, who were recruited using a similar procedure. For DAT, MAOA, MAOB polymorphisms, similar allelic frequencies were present in familial, sporadic PD and control patients. In contrast, at the DRD2 locus, the overall allelic distribution was significantly different in the sporadic PD (p < 0.01) and in the familial PD groups (p < 0.05), each was compared with the controls. The odd ratios were significant (p < 0.01) in sporadic PD and in familial PD for allele 3 with respective values of 1.84 (95% CI, 1.23-2.74) and 2.83 (95% CI, 1.32-6.08). Individuals who were homozygous for allele 3 were 2.3 times more frequent in the sporadic PD than in controls. Results suggest that DRD2, but not DAT, MAOA and MAOB, might be a genetic determinant of PD in the population tested.

Alleles↗

PubMed2001

Dopamine D2 receptor gene (DRD2) is associated with alcoholism with conduct disorder.

This study examined whether there is evidence for an association between alcoholism with conduct disorder and alleles of the TaqI A and TaqI B polymorphisms, both individually and as haplotypes, at the dopamine D2 receptor gene (DRD2). We studied 182 Han Chinese subjects, including 34 alcoholics with conduct disorder, 63 alcoholics without conduct disorder, and 85 nonalcoholics. Alcohol dependence and conduct disorder were defined according to DSM-III-R criteria. Significant associations were observed between TaqI A and TaqI B at the DRD2 locus, tested individually and as haplotypes, and alcoholism with conduct disorder. Our results suggested that DRD2 might be associated with conduct disorder or a predisposition to both conduct disorder and alcoholism. However, this needs to be further investigated by examining the differences among conduct disorder with alcoholism, conduct disorder only, and controls for the TaqI A and B system at DRD2.

Adult↗

PubMed2025

The importance of dopamine levels and single-nucleotide polymorphism within COMT, DRD1 and DRD2 genes in obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a prevalent sleep disorder that contributes to serious cardiovascular comorbidities. While the mechanical aspects of OSA are well-studied, its neurobiological underpinnings remain underexplored. In this study, we investigated the role of dopamine and its genetic modulators in OSA pathophysiology. PATIENTS AND METHODS: Serum dopamine levels were assessed in a cohort of 153 participants (96 OSA patients and 57 controls), and single-nucleotide polymorphisms (SNPs) in dopamine-related genes, including COMT, DRD1 and DRD2, were analysed in a cohort of 286 participants (141 OSA patients and 145 controls). RESULTS: Elevated serum dopamine levels were observed in OSA patients (p = 0.01), with dopamine levels correlating independently with OSA and male gender. Genotypic analysis identified the DRD2 rs1800497 T allele as a potential independent predictor of OSA severity (p = 0.011), hypopnea (p = 0.005) and arousals (p = 0.024). CONCLUSIONS: This study advances the understanding of OSA by identifying elevated dopamine levels and genetic variations in DRD2 rs1800497 as potential modulators of its occurrence and severity. These findings pave the way for personalized diagnostic and therapeutic approaches. By integrating neurobiology, genetics, and clinical practice, this research contributes to the evolving framework for precision medicine in sleep disorders.

Humans↗

PubMed2000

Allelic association between the DRD2 TaqI A polymorphism and Parkinson's disease.

Genes encoding proteins involved in dopaminergic transmission have been of special interest during the evaluation of candidate genes for Parkinson's disease (PD). The dopamine D2 receptor gene (DRD2) is located on chromosome 11 q22-q23, and several polymorphisms of the gene have been described. The DRD2 gene has a TaqI A restriction fragment length polymorphism that is located in the untranslated region, approximately 10 kilobases from the 3' end of the gene. This polymorphism creates the two alleles A1 (variant) and A2. In this study, we investigated the hypothesis that a TaqI repeat fragment length polymorphism in the dopamine D2 receptor gene may be associated with PD. DNA from 72 patients with PD, classified as definite, probable, or atypical PD, and from 81 controls was genotyped by polymerase chain reaction and gel electrophoresis for the presence of the TaqI A1 polymorphism. The controls were matched for age, race, and geographic origin. There were significant differences in allelic distribution between the overall PD group and control groups (chi2 = 5.009, p = 0.025). When only patients with definite PD were considered an even more significant association was found (chi2 = 8.2121, p = 0.004). Among the overall PD group, the odds ratio for having the variant allele A1 was found to be 2.2 (95% confidence interval, [1.1; 4.4]), whereas it was calculated to be 3.0 (95% confidence interval, [1.4; 6.4]) when only patients with definite PD were considered. The current study showed that there is a statistically significant association between the DRD2 variant allele A1 and PD. This association is most pronounced in patients with definite PD and becomes nonsignificant when the clinical picture is classified as atypical PD.

Aged↗

PubMed2003

Ethanol consumption and DRD2 gene TaqI a polymorphism among socially drinking males.

The dopaminergic system in the human brain is thought to play a major role in the development of alcohol consumption habits and alcoholism. It has been reported that homozygous D2-/- knock-out mice lacking D2 receptors consume about 50% to 60% less ethanol than wild-type D2+/+ mice, and heterozygous mice have an intermediate level of alcohol consumption. The DRD2 gene TaqI A polymorphism has been suggested to associate with a low D2 receptor density in post mortem and in vivo measurements. Numerous association studies on this polymorphism and alcoholism have shown most controversial results. We studied whether DRD2 TaqI A genotype affects alcohol consumption in an ethnically homogeneous, representative sample of 1,019 Finnish Caucasian males. After excluding the abstainers from the study, the self-reported alcohol consumption among the remaining 884 non-abstainers was compared in the TaqI A genotype groups (A1/A1, A1/A2, A2/A2). The alcohol consumption of the homozygous A1/A1 group was about 30% lower than in A1/A2 group, and 40% lower than in A2/A2 group (P = 0.042 and 0.041 in a sociodemographic variable-adjusted multivariate model). The results indicate an association between DRD2 genotype and alcohol consumption habits in humans. These results in the large sample of non-alcoholic males are also opposite to some previous findings on the higher A1 allele frequency among alcoholic populations.

Alcohol Drinking↗

PubMed2006

Effects of DRD2 and CYP2D6 genotypes on delta EEG power response to aripiprazole in healthy male volunteers: a preliminary study.

The aim of the present study was to evaluate the effects of polymorphisms in dopamine D2 receptor (DRD2) and cytochrome P450 (CYP) 2D6 genes on delta EEG power response to aripiprazole in healthy male volunteers. Seventeen volunteers were recruited according to the DRD2 Taq1A genotype, and separated into the following groups: homozygous wild-type (A2/A2, n = 7), heterozygous (A2/A1, n = 5) and homozygous variant-type (A1/A1, n = 5) groups. After enrollment in this study, they were genotyped for CYP2D6. The volunteers received single 10 mg oral doses of aripiprazole, in accordance with an open-label parallel group study design. Plasma levels of aripiprazole and its metabolite were determined and EEGs were obtained simultaneously. The pharmacodynamic parameter was absolute delta power in the Cz channel. The changes of delta power were not different according to DRD2 Taq1A genotypes. As to the CYP2D6 allele, the subjects had the following CYP2D6 genotypes: *10/*10 (n = 4), *1/*10 (n = 5), *1/*5 (n = 2), *1/*1 (n = 3), *2/*41 (n = 1), *2/*2 (n = 1), *2N/*10 (n = 1). Subjects exhibiting the *1/*5 and *1/*10 genotypes showed a trend toward high area under the plasma aripiprazole concentration-time curve (AUC), which was linearly related to area under the EEG response-time curve (AUEC). Our results demonstrate a need for further evaluation of the CYP2D6 genotypic effect on the pharmacodynamics of aripiprazole.

Adult↗

PubMed1993

The dopamine D2 receptor (DRD2) as a major gene in obesity and height.

Dopamine plays a major role in the regulation of appetite and growth hormone. Dopaminergic agonists suppress appetite and dopamine D2 receptor antagonists enhance it. We examined the hypothesis that allelic variants of the DRD2 locus may be associated with weight and height. Sarkar and Sommer described two DRD2 polymorphisms that could be haplotyped by PCR. For weight, the mean Z score (National Center for Health Statistics) for 208 subjects without haplotype 4 was 0.086 versus 0.557 for 280 subjects with haplotype 4, P = 0.0003. Two separate sets of subjects were studied and these results were significant for both, providing an internal replication. For height, the mean Z score for 164 subjects without haplotype 4 was 0.1677 versus 0.6885 for 219 subjects with haplotype 4, P < 0.00001. These and other data suggest that the 4 haplotype is in linkage disequilibrium with allelic variants of the DRD2 gene that play a major role in the regulation of weight (obesity) and height, and may serve as a risk factor in late-onset non-insulin-dependent diabetes mellitus (NIDDM).

Adolescent↗

PubMed2000

Prolactin response to nemonapride, a selective antagonist for D2 like dopamine receptors, in schizophrenic patients in relation to Taq1A polymorphism of DRD2 gene.

The dopamine D2 receptor (DRD2) gene has a Taq1A restriction fragment length polymorphism yielding two alleles, A1 and A2. It has been shown that the subjects with less frequent allele, the A1 allele, have lower density and diminished function of DRD2 in the striatum, compared to those with no A1 allele. In the present study, the relationship between this polymorphism and prolactin response to nemonapride, an antipsychotic drug with selective and potent DRD2 antagonistic property, was investigated in 25 Japanese schizophrenic inpatients (13 males, 12 females). The daily dose of nemonapride was fixed at 18 mg, and the duration of treatment was 3 weeks. Taq1A genotypes were determined by the polymerase chain reaction method. Plasma prolactin concentrations were measured by enzyme immunoassay. The subjects were divided into four subgroups by gender and Taq1A genotypes, i.e., six males and eight females with the A1 allele, seven males and four females with no A1 allele. The (delta)prolactin (change from the pretreatment concentration) at 1 week was significantly (P<0.05) higher in females with the A1 allele (78.0 +/- 47.1 ng/ml) than in males with the A1 allele (33.4 +/- 14.0 ng/ml) or with no A1 allele (29.5+/-24.8 ng/ml). In addition, (delta)prolactin at 3 weeks was significantly (P<0.05) higher in females with the A1 allele (98.1+/-67.9 ng/ml) than in females with no A1 allele (33.4+/-24.6 ng/ml), males with the A1 allele (29.1+/-17.3 ng/ml) or males with no A1 allele (28.6+/-22.0 ng/ml). The present study thus suggests that female patients with the A1 allele show a greater prolactin response to nemonapride, who may have a high risk for adverse effects associated with neuroleptic-induced hyperprolactinemia.

Adolescent↗