Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dopamine D4 receptor gene (DRD4 gene) is one of the important candidate genes for schizophrenia and other psychoses. In humans, several alleles with variable repeat numbers of a 48-base-pair element within the third exon are known. The corresponding receptor proteins differ in their pharmacological properties. It might be possible that specific alleles or genotypes predispose for schizophrenia and other psychoses. The aim of the present study was to investigate and compare the frequency of the DRD4 alleles and genotypes in healthy controls and patients suffering from schizophrenia, schizoaffective or affective disorders. The DRD4 subtypes of 92 controls, 91 patients with schizophrenia, 90 patients with affective and 20 with schizoaffective disorders were identified by a combination of Southern blot technique and PCR. Statistical analysis revealed several significant differences between controls and patients, e.g. an increased frequency of the D4.7 allele among patients with schizophrenia, schizoaffective or unipolar affective disorder. The results indicate a possible role of the DRD4 gene polymorphism in the pathophysiology of psychotic diseases. When a part of the DRD4 gene sequence containing the codons for the most important amino acids for dopamine binding in 9 controls, 9 patients with schizophrenia and 10 with affective disorders were compared, no differences could be found.
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PMID:Association between different psychotic disorders and the DRD4 polymorphism, but no differences in the main ligand binding region of the DRD4 receptor protein compared to controls. 935 44

The human dopamine D4 receptor gene (DRD4) is an important candidate gene for schizophrenia. We identified a novel -521C>T polymorphism in the 5'-promoter region of DRD4. A transient expression method revealed that the T allele of this polymorphism reduces the transcriptional efficiency by 40% compared with the C allele. This polymorphism is of interest because of reported elevation of D4-like sites and DRD4 mRNA in the postmortem schizophrenic brain. The C allele frequency was significantly higher in 252 Japanese schizophrenics (0.48) than in 269 Japanese controls (0.41) (p = 0. 02) [odds ratio = 1.35 (95% confidence interval 1.05 - 1.72)]. Although the association is weak and should be considered tentative until other studies replicate it, this polymorphism provides a tool with the potential to examine whether DRD4 is related to susceptibility to and neuroleptic response in schizophrenia.
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PMID:A genetic polymorphism in the promoter region of DRD4 associated with expression and schizophrenia. 1032 80

The dopamine D4 receptor (DRD4) may play a role in the pathogenesis of neuropsychiatric disease and in the action of dopaminergic drugs. The 48-bp repeat polymorphism (48-bp VNTR) coding for a 16-amino acid segment in the third cytoplasmatic loop of the DRD4 was studied as a predictor of the therapeutic response to antipsychotics and as susceptibility factor for schizophrenia. We included 638 in-patients with acute schizophrenic, schizoaffective (mainly schizophrenic), and other nonaffective psychoses, as well as two reference groups: one with 278 in-patients with non-psychiatric diseases, and one with 474 healthy volunteers. Catatonic patients (DSM-IV 295.2) more frequently carried the DRD4 D4.2 and D4.3 allele than did all other schizophrenic cases (P < 0.001; OR: 2.7; CI: 1.5-4.9) and controls (P < 0.004; OR: 2.3; CI: 1.3-4.2). We found no significant difference in the DRD4 allele or in genotype frequencies in our comparison of all schizophrenic patients and controls. The subgroups with affected family members, and the subgroups with early or late onset of disease, also did not differ from the controls in DRD4 allele frequencies. The 48-bp VNTR was not a predictor for therapeutic outcome measured by the positive and negative symptoms scale. A total of 1390 subjects showed between 1 and 10 repeats (D4. 1 and D4.10), with 25 different genotypes. These data exclude a major role of DRD4 48-bp VNTR in response to antipsychotic therapy and as susceptibility factor for schizophrenia, but catatonic schizophrenia may be associated with the D4.2 and D4.3 alleles.
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PMID:Dopamine D4 receptor 48-bp repeat polymorphism: no association with response to antipsychotic treatment, but association with catatonic schizophrenia. 1088 53

The human dopamine D4 receptor (DRD4) is of major interest in molccular studies of schizophrenia and personality traits. We examined the association of schizophrenia and polymorphisms in the upstream region of the DRD4 gene (-768G>A in the negative modulator region; -521C>T, -376C >T, and -291C>T in the cell type-specific promoter region; and -616C>G between the two regions) in 208 schizophrenic patients and 210 normal controls. No significant difference in genotype and allele frequencies was observed between the two groups, indicating that these polymorphisms do not make a major contribution to the pathogenesis of schizophrenia. We also studied the association of polymorphisms in the upstream region and a 48-bp repeat polymorphism in exon III of the DRD4 gene with personality traits in 173 Japanese individuals who completed the temperament and character inventory (TCI). The -768G>A polymorphism was significantly associated with reward dependence (P= 0.044), while no significant association was observed between novelty seeking and polymorphisms in the upstream region or the exon III repeat polymorphism of the DRD4 gene.
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PMID:Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene (DRD4) with schizophrenia and personality traits. 1128 15

alpha(2) adrenergic receptors are activated by adrenaline and noradrenaline, and three subtypes (ie, A, B, C) have differential affinities for antagonists and medications. The alpha(2c) adrenergic receptor (ADRA2C), located on chromosome 4p16.3, is a candidate gene for schizophrenia because it binds clozapine, an atypical neuroleptic useful for treatment-resistant schizophrenia. In addition, ADRA2C binds clonidine which is prescribed for three psychiatric diseases. This report communicates the findings of the genetic scanning of this gene of very tough GC content. The complete coding sequences and splice junctions were scanned with [DOVAM]-S in 104 schizophrenics, and pilot probes of patients with alcoholism (41 patients), cocaine abuse (25 patients), puerperal psychosis (30 patients), attention deficient/hyperactivity disorder (25 patients) and autism (25 patients). Six sequence variants were found, including five silent polymorphisms (allele frequencies 0.6--25%) and an in-frame deletion of a homologous repeat at nucleotides 967--978 (ie, TIDRU(1)). Genotyping of the normal two repeat unit of the Third Intracytoplasmic Domain Repeat Unit (TIDRU(2)) and the deleted variant (TIDRU(1)) revealed that TIDRU(1) had allelic frequencies of 39% (11/28) and 3.5% (6/172) in African-American and Caucasian schizophrenics, respectively, and it occurred with equal frequency in controls (44%, 31/70 and 3.0%, 6/198). TIDRU(1) occurs at a location similar to the third intracytoplasmic 48-nucleotide repeat unit in the DRD4 that is associated with ADHD. Although these data do not suggest an association of TIDRU(1) with schizophrenia, additional studies are needed to see whether TIDRU(1) confers a clinical phenotype.
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PMID:An in-frame deletion in the alpha(2C) adrenergic receptor is common in African--Americans. 1131 18

We previously reported an association of DRD4 exon3 long allele variants with delusional symptomatology independently from diagnoses. The aim of this investigation was to study DRD4 in major psychoses and to test the association in a larger sample. We studied 2,011 inpatients affected by bipolar disorder (n = 811), major depressive disorder (n = 635), schizophrenia (n = 419), delusional disorder (n = 104), psychotic disorder not otherwise specified (n = 42), and 601 healthy controls. A subsample of 1,264 patients were evaluated using the OPCRIT checklist and differences of symptomatology factor scores among genetic variants were assessed using one-way analysis of variance (ANOVA). DRD4 allele and genotype frequencies in bipolars, schizophrenics, delusionals, and psychotic NOS were not significantly different from controls; major depressives showed a trend toward an excess of DRD4*Short and DRD4*Short/Short variants versus controls. The ANOVA on factor scores in the whole subsample of 1,264 subjects showed a significant difference on delusion factor in allele analysis (P = 0.007), and in genotype one (P = 0.018), with DRD4*Long containing variants associated with severe symptomatology. The analysis in the replication subjects only (n = 803) showed a trend in the same direction, though not reaching the significance level. This analysis in an enlarged sample suggests that DRD4*Long alleles exert a small but significant influence on the delusional symptomatology in subjects affected by major psychoses.
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PMID:DRD4 exon 3 variants associated with delusional symptomatology in major psychoses: a study on 2,011 affected subjects. 1135 51

The -521C/Tsingle nucleotide polymorphism (SNP) in the promoter region of the dopamine D4 receptor gene (DRD4) has recently been detected in oriental (Japanese) individuals and related to novelty seeking and schizophrenia. Here, we report the analysis of the -521C/T polymorphism in a Caucasian (Hungarian) population using two independent genotyping methods. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure utilized the Fspl restriction site around the -521 position. An additional, nonpolymorphic cleavage site was also included into the amplified region to serve as an internal standard for verifying the completion of the digestion. As another independent method, a tetraprimer system for single-tube allele-specific PCR (SAS-PCR) was developed to generate -521C and -521T specific PCR products with different fragment sizes. Consequently, genotyping with SAS-PCR is based on the gel-electrophoretic separation of the allele-specific double-stranded DNA (dsDNA) fragments. 119 healthy Hungarian individuals were genotyped for -521C/T polymorphism of the dopamine D4 promoter region, using both methods. Similar allele frequencies were found (-521C allele: 0.43; -521T allele: 0.57) as reported earlier for the Japanese population.
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PMID:Genotyping the -521C/T functional polymorphism in the promoter region of dopamine D4 receptor (DRD4) gene. 1135 33

The dopamine D(4) receptor has been implicated in the pathogenesis of schizophrenia. An association between a putative functional promoter polymorphism (-521C/T) in the dopamine D(4) receptor gene (DRD4) and schizophrenia was recently reported. In the present study, patients with schizophrenia (n = 132) and control subjects (n = 388) were analyzed with respect to the DRD4 - 521C/T polymorphism. No significant case control differences emerged. The present results do not support a major role for DRD4 in the etiology of schizophrenia among Caucasians from Sweden.
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PMID:No association between a promoter dopamine D(4) receptor gene variant and schizophrenia. 1149 69

The goal of the present study was to use a meta-analysis on previous studies plus our own unpublished data to confirm and extend findings which indicate that the variation in the dopamine D4 receptor (DRD4) gene is best represented by a mixture of two different ethnic groups. The genotype distribution was divided into either a long or short form using a mixture analysis of normal controls of different ethnic origins under the assumption that there is a single major gene. The meta-analysis was based on the data from 19 independent samples, 18 association studies, and from our own unpublished data, including a total of 1431 schizophrenic patients (sporadic cases 1309, familial cases 122) and 1439 controls. No significant genotype differences were noted between patients and controls for the whole sample. However, reorganization of the studies into different groups by the geographical origin of samples revealed significant ethnic heterogeneity. In addition, there was a significant association between the long form of DRD4 gene and schizophrenia in Caucasians, especially those with familial schizophrenia.
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PMID:Ethnic heterogeneity in allele variation in the DRD4 gene in schizophrenia. 1222 55

This study examined the possible association between the polymorphism in the dopamine receptor DRD4 gene and response to risperidone among 24 Israeli Jewish adolescent inpatients with first-episode schizophrenia. Response was categorically determined by a change of >40% on the Brief Psychiatric Rating Scale (BPRS). No significant association was found between the DRD4 genotype and clinical response, although carriers of <7 repeat alleles demonstrated higher response rate (10/20 vs. 0/4, P=0.11). Studies in larger groups of adolescent schizophrenia patients are warranted to clarify the possible association between DRD4 exon III repeat alleles and the response to risperidone.
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PMID:DRD4 exon III polymorphism and response to risperidone in Israeli adolescents with schizophrenia: a pilot pharmacogenetic study. 1272 44


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