No evidence for association of dopamine D2 receptor variant (Ser 311/Cys311) with major psychosis

Sasaki, Tsukasa; Macciardi, Fabìo; Badri, Farideh; Verga, M.; Meltzer, Herbert Y.; Lieberman, Jeffrey A.; Howard, Alfreda; Bean, Graham; Joffe, Russel T.; Hudson, Craig J.; Kennedy, James L.

doi:10.1002/(sici)1096-8628(19960726)67:4<415::aid-ajmg18>3.0.co;2-m

Cited by 35 publications

(24 citation statements)

References 4 publications

(2 reference statements)

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“…19 Following this hypothesis, a symptomatologic analysis has been performed using SADS items on a small sample of schizophrenics and no association was detected. 53 We did not replicate the finding in a preliminary report using the DRD2 VNTR marker in a sample of 47 bipolar subjects. 54 However, we reported and confirmed an association of DRD2* S311C with disorganized symptomatology in a large sample of 267 schizophrenics and delusional subjects.…”

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confidence: 59%

Dopamine receptor D2 Ser/Cys 311 variant is associated with delusion and disorganization symptomatology in major psychoses

et al. 2000

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The D2 receptor (DRD2) is a binding site of many psychoactive drugs and it has been proposed as a genetic risk factor for psychiatric disorders. The aim of this investigation was to study the DRD2 S311C variant in major psychoses. We studied 1182 inpatients with diagnoses of bipolar disorder (n = 480), major depressive disorder (n = 269), schizophrenia (n = 366), delusional disorder (n = 44), psychotic disorder not otherwise specified (n = 23) and 267 healthy controls. Eight hundred and eighty-seven subjects were also scored for their lifetime symptomatology using the the Operational Criteria checklist for psychotic illness (OPCRIT). DRD2 variants were not associated with affected subjects even when possible confounders like gender and onset were considered. When we considered the 887 subjects with the symptomatologic analysis, we observed a significant association of the DRD2 S311C variant with both delusion and disorganization features. The association was present independently from diagnoses. Our results do not show that coding variants of the DRD2 S311C play a major role in conferring susceptibility to major psychoses, but they may be connected with disorganized and delusional symptomatology independently from diagnoses. Molecular Psychiatry (2000) The D2 receptor is the major binding site of many typical and atypical neuroleptic drugs and its gene has been cloned and mapped to 11q22-23.2 Itokawa et al 3 reported a polymorphism causing a structural change from Serine to Cysteine at codon 311 of DRD2 (S311C); this substitution occurs in the third intracellular loop of the receptor. Preliminary results showed that DRD2 rarer TaqI variants were associated with higher levels of the monoamine metabolites homovanillic acid and 3-methoxy-4-hydroxyphenylglycol in lumbar cerebrospinal fluid in controls. 4 S311C has been proposed as Correspondence: A Serretti MD,

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confidence: 59%

Dopamine receptor D2 Ser/Cys 311 variant is associated with delusion and disorganization symptomatology in major psychoses

et al. 2000

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“…Our findings for TaqI-A and Ser311Cys polymorphisms do not corroborate previous findings obtained with case-control association studies (Arinami et al, 1994(Arinami et al, , 1996 and meta-analysis (Jonsson et al, 2003a). However, they are in agreement with case-control association studies carried out in different populations (Itokawa et al, 1993;Sasaki et al, 1996;Tanaka et al, 1996;Spurlock et al, 1998;Hori et al, 2001;Himei et al, 2002). Other authors also have obtained inconsistent results with association studies with the y141C InsyDel polymorphism at the DRD2 gene (Li et al, 1998;Breen et al, 1999;Jonsson et al, 1999;Himei et al, 2002).…”

Section: Discussioncontrasting

confidence: 50%

Family association study between DRD2 and DRD3 gene polymorphisms and schizophrenia in a Portuguese population

Ambrosio

Kennedy

Macciardi

et al. 2004

Psychiatry Research

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Schizophrenia is a highly heritable condition, as demonstrated in family, twin and adoption studies. Candidate genes from the dopaminergic system have long been hypothesized to be involved in the etiology of this disorder. In the present study, we investigated the genetic association between polymorphisms in the D2 and D3 dopamine receptor (DRD2, DRD3) genes and schizophrenia. We examined 90 trios from Portugal, and negative results were obtained from association studies with both Haplotype Relative Risk (HRR) and Transmission Disequilibrium Test (TDT), as well as TRANSMIT. Therefore, we conclude that neither the DRD2 nor the DRD3 gene polymorphisms investigated are associated with schizophrenia in our sample.

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“…In previous reports the fre-quency of schizophrenic individuals heterozygous for Cys 311 varied between 3.6% up to 8.5% in Asian populations 32,[47][48][49][50][51] and was less frequent (1.8-5.0%) in Caucasians. 46,[52][53][54][55][56][57][58] Arinami et al 32 firstly reported a significantly increased allele frequency of the cysteine allele in schizophrenic Japanese patients (5.4%) compared to controls (1.8%). Furthermore, the age of onset was lower in patients with the cysteine allele and most of the allele carriers had a positive family history.…”

Section: Discussionmentioning

confidence: 99%

Relationship between adverse effects of antipsychotic treatment and dopamine D2 receptor polymorphisms in patients with schizophrenia

Kaiser

Klufmöller

et al. 2002

Mol Psychiatry

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Extrapyramidal adverse symptoms (EPS) represent a major type of adverse events in treatment with typical antipsychotic drugs which share high affinity to the dopamine D 2 receptor (DRD2). Genetic variants of this receptor may modulate the therapeutic response and the severity of adverse symptoms of antipsychotics. We analyzed nine known polymorphisms of the DRD2 in 665 schizophrenic patients with European Caucasian ethnic background and compared the intensity of acute dystonia, extrapyramidal symptoms, akathisia, and tardive dyskinesia between carriers of different DRD2 genotypes. In a subgroup of 40 patients with most severe extrapyramidal symptoms we sequenced the coding region including the exonintron junctions of the DRD2 gene. Functionally relevant DRD2 amino acid variants (Ser 310 , Cys 311 ) were rare or were not found at all (Ala 96 ). Complete sequence analysis of sufferers from the most severe adverse effects revealed two new intronic polymorphisms and a silent polymorphism in exon 7, but no new amino acid variants beyond those which are already known. We found no significant association between these polymorphisms and the intensity of the different types of adverse neurologic effects of the antipsychotics. These results were obtained by correlating adverse events with each of the nine single nucleotide polymorphisms and by correlation with the estimated haplotypes. In conclusion, genetic variations in the DRD2 gene were no major predictors of the individually variable adverse effects from antipsychotic treatment in Caucasian schizophrenic patients.

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No evidence for association of dopamine D2 receptor variant (Ser 311/Cys311) with major psychosis

Cited by 35 publications

References 4 publications

Dopamine receptor D2 Ser/Cys 311 variant is associated with delusion and disorganization symptomatology in major psychoses

Dopamine receptor D2 Ser/Cys 311 variant is associated with delusion and disorganization symptomatology in major psychoses

Family association study between DRD2 and DRD3 gene polymorphisms and schizophrenia in a Portuguese population

Relationship between adverse effects of antipsychotic treatment and dopamine D2 receptor polymorphisms in patients with schizophrenia

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