-141 C Del/Ins polymorphism of the dopamine receptor 2 gene is associated with schizophrenia in a British population

G Breen, J Brown, S Maude, H Fox, D Collier, T Li, M Arranz, D Shaw, D St Clair

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Dopamine has long been hypothesised to be involved in the pathogenesis of schizophrenia. The dopamine D2 receptor is a major site of action of neuroleptic agents used in the treatment of schizophrenia. Arinami et al. [1997; Human Mol Genet 6:577-582] have recently sequenced the dopamine receptor 2 (DRD2) gene in Japanese individuals and identified a novel polymorphism: a single cytosine deletion at position -141 disrupting a BstN1 restriction site with a frequency of 0.22 in their control group. They then found a strong association with this polymorphism and schizophrenia (p < 0.001) with an odds ratio of 0.60 in a Japanese population. We have attempted to verify their results by repeating the RFLP analysis on a sample of Scottish schizophrenics and controls. We then combined our data with those from another British sample recruited using similar procedures. The total combined sample size was 439 schizophrenics and 437 controls, We obtained a significant association-p = 0.02 with an odds ratio of 1.41. Schizophrenia is associated with the C insertion in the Japanese, but that association is reversed in Caucasians, Linkage disequilibrium with a causative polymorphism nearby is the most likely explanation for this reverse association. Am. J. Med. Genet, (Neuropsychiatr, Genet.) 88:407-410, 1999, (C) 1999 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)407-410
Number of pages4
JournalAmerican Journal of Medical Genetics
Volume88
Publication statusPublished - 1999

Keywords

  • dopamine
  • schizophrenia
  • DRD2 gene
  • association
  • insertion
  • linkage disequilibrium
  • AFFECTIVE-DISORDERS
  • MOLECULAR VARIANT
  • SER311/CYS311
  • PSYCHOSIS

Cite this

-141 C Del/Ins polymorphism of the dopamine receptor 2 gene is associated with schizophrenia in a British population. / Breen, G ; Brown, J ; Maude, S ; Fox, H ; Collier, D ; Li, T ; Arranz, M ; Shaw, D ; St Clair, D .

In: American Journal of Medical Genetics, Vol. 88, 1999, p. 407-410.

Research output: Contribution to journalArticle

@article{9d3e739b691f411daebc80b45811059f,
title = "-141 C Del/Ins polymorphism of the dopamine receptor 2 gene is associated with schizophrenia in a British population",
abstract = "Dopamine has long been hypothesised to be involved in the pathogenesis of schizophrenia. The dopamine D2 receptor is a major site of action of neuroleptic agents used in the treatment of schizophrenia. Arinami et al. [1997; Human Mol Genet 6:577-582] have recently sequenced the dopamine receptor 2 (DRD2) gene in Japanese individuals and identified a novel polymorphism: a single cytosine deletion at position -141 disrupting a BstN1 restriction site with a frequency of 0.22 in their control group. They then found a strong association with this polymorphism and schizophrenia (p < 0.001) with an odds ratio of 0.60 in a Japanese population. We have attempted to verify their results by repeating the RFLP analysis on a sample of Scottish schizophrenics and controls. We then combined our data with those from another British sample recruited using similar procedures. The total combined sample size was 439 schizophrenics and 437 controls, We obtained a significant association-p = 0.02 with an odds ratio of 1.41. Schizophrenia is associated with the C insertion in the Japanese, but that association is reversed in Caucasians, Linkage disequilibrium with a causative polymorphism nearby is the most likely explanation for this reverse association. Am. J. Med. Genet, (Neuropsychiatr, Genet.) 88:407-410, 1999, (C) 1999 Wiley-Liss, Inc.",
keywords = "dopamine, schizophrenia, DRD2 gene, association, insertion, linkage disequilibrium, AFFECTIVE-DISORDERS, MOLECULAR VARIANT, SER311/CYS311, PSYCHOSIS",
author = "G Breen and J Brown and S Maude and H Fox and D Collier and T Li and M Arranz and D Shaw and {St Clair}, D",
year = "1999",
language = "English",
volume = "88",
pages = "407--410",
journal = "American Journal of Medical Genetics",
issn = "0148-7299",
publisher = "Wiley",

}

TY - JOUR

T1 - -141 C Del/Ins polymorphism of the dopamine receptor 2 gene is associated with schizophrenia in a British population

AU - Breen, G

AU - Brown, J

AU - Maude, S

AU - Fox, H

AU - Collier, D

AU - Li, T

AU - Arranz, M

AU - Shaw, D

AU - St Clair, D

PY - 1999

Y1 - 1999

N2 - Dopamine has long been hypothesised to be involved in the pathogenesis of schizophrenia. The dopamine D2 receptor is a major site of action of neuroleptic agents used in the treatment of schizophrenia. Arinami et al. [1997; Human Mol Genet 6:577-582] have recently sequenced the dopamine receptor 2 (DRD2) gene in Japanese individuals and identified a novel polymorphism: a single cytosine deletion at position -141 disrupting a BstN1 restriction site with a frequency of 0.22 in their control group. They then found a strong association with this polymorphism and schizophrenia (p < 0.001) with an odds ratio of 0.60 in a Japanese population. We have attempted to verify their results by repeating the RFLP analysis on a sample of Scottish schizophrenics and controls. We then combined our data with those from another British sample recruited using similar procedures. The total combined sample size was 439 schizophrenics and 437 controls, We obtained a significant association-p = 0.02 with an odds ratio of 1.41. Schizophrenia is associated with the C insertion in the Japanese, but that association is reversed in Caucasians, Linkage disequilibrium with a causative polymorphism nearby is the most likely explanation for this reverse association. Am. J. Med. Genet, (Neuropsychiatr, Genet.) 88:407-410, 1999, (C) 1999 Wiley-Liss, Inc.

AB - Dopamine has long been hypothesised to be involved in the pathogenesis of schizophrenia. The dopamine D2 receptor is a major site of action of neuroleptic agents used in the treatment of schizophrenia. Arinami et al. [1997; Human Mol Genet 6:577-582] have recently sequenced the dopamine receptor 2 (DRD2) gene in Japanese individuals and identified a novel polymorphism: a single cytosine deletion at position -141 disrupting a BstN1 restriction site with a frequency of 0.22 in their control group. They then found a strong association with this polymorphism and schizophrenia (p < 0.001) with an odds ratio of 0.60 in a Japanese population. We have attempted to verify their results by repeating the RFLP analysis on a sample of Scottish schizophrenics and controls. We then combined our data with those from another British sample recruited using similar procedures. The total combined sample size was 439 schizophrenics and 437 controls, We obtained a significant association-p = 0.02 with an odds ratio of 1.41. Schizophrenia is associated with the C insertion in the Japanese, but that association is reversed in Caucasians, Linkage disequilibrium with a causative polymorphism nearby is the most likely explanation for this reverse association. Am. J. Med. Genet, (Neuropsychiatr, Genet.) 88:407-410, 1999, (C) 1999 Wiley-Liss, Inc.

KW - dopamine

KW - schizophrenia

KW - DRD2 gene

KW - association

KW - insertion

KW - linkage disequilibrium

KW - AFFECTIVE-DISORDERS

KW - MOLECULAR VARIANT

KW - SER311/CYS311

KW - PSYCHOSIS

M3 - Article

VL - 88

SP - 407

EP - 410

JO - American Journal of Medical Genetics

JF - American Journal of Medical Genetics

SN - 0148-7299

ER -