Insertion/deletion variant (−141C Ins/Del) in the 5′ regulatory region of the dopamine D2 receptor gene: lack of association with schizophrenia and bipolar affective disorder

Summary. A possible dysregulation of dopaminergic neurotransmission has been implicated in the aetiology of schizophrenic psychoses, in particular of paranoid-hallucinatory states, and of the manic episodes of bipolar affective disorder. In the present study we analysed allelic and genotypic variations of a recently described functional deletion/insertion variant (−141C Ins/Del) in the 59 flanking region of the human dopamine D2 receptor gene. We investigated a total of 620 unrelated individuals, comprising 260 schizophrenic patients, 70 patients with bipolar affective disorder, and 290 population controls. Analysis of the −141C Ins/Del variant revealed that the schizophrenic, bipolar affective and control groups did not differ significantly regarding genotype frequencies and allele frequencies. No evidence of an allelic association with either a family history of schizophrenic psychosis or a diagnosis of schizophrenia of the paranoid type (according to ICD 10) was found. Our findings indicate that the −141C Del variant in the 5′ flanking region of the human dopamine D2 receptor gene is unlikely to play a substantial role in genetic predisposition to major psychiatric disorders in Caucasians.

[1]  K. Kidd,et al.  No linkage between D2 dopamine receptor gene region and schizophrenia. , 1991, Archives of general psychiatry.

[2]  R. Todd,et al.  Analysis of the Structure and Expression of the Human Dopamine D2A Receptor Gene , 1991, Journal of neurochemistry.

[3]  C. Larsson,et al.  Normal structural dopamine type 2 receptor gene in prolactin-secreting and other pituitary tumors. , 1994, The Journal of clinical endocrinology and metabolism.

[4]  J. Mallet,et al.  Transcription of the rat dopamine-D2-receptor gene from two promoters. , 1994, European journal of biochemistry.

[5]  D. Grandy,et al.  Cloning of the cDNA and gene for a human D2 dopamine receptor. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[6]  F. Bloom,et al.  Psychopharmacology: The Fourth Generation of Progress , 1995 .

[7]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[8]  A. Cravchik,et al.  Antagonist binding characteristics of the Ser311-->Cys variant of human dopamine D2 receptor in vivo and in vitro. , 1997, Biochemical and biophysical research communications.

[9]  Alberto Piazza,et al.  The History and Geography of Human Genes: Abridged paperback Edition , 1996 .

[10]  E. Smeraldi,et al.  No association of the Ser/Cys311 DRD2 molecular variant with schizophrenia using a classical case control study and the haplotype relative risk , 1997, Schizophrenia Research.

[11]  A Carlsson,et al.  The current status of the dopamine hypothesis of schizophrenia. , 1988, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[12]  S. Kanba,et al.  Linkage studies between affective disorder and dopamine D2, D3, and D4 receptor gene loci in four Japanese pedigrees , 1994, Psychiatry Research.

[13]  T. Arinami,et al.  A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. , 1997, Human molecular genetics.

[14]  T. Minowa,et al.  Negative modulator of the rat D2 dopamine receptor gene. , 1994, The Journal of biological chemistry.

[15]  A. Rolfs,et al.  Dopamine D2 receptor gene (DRD2) haplotypes in Caucasians. , 1996, Gene.

[16]  H. Maeno,et al.  Dopamine Receptors , 2018 .

[17]  M. Itokawa,et al.  Association of dopamine D2 receptor molecular variant with schizophrenia , 1994, The Lancet.

[18]  D. Sibley,et al.  Functional Analysis of the Human D2 Dopamine Receptor Missense Variants* , 1996, The Journal of Biological Chemistry.

[19]  T. Minowa,et al.  Analysis of the promoter region of the rat D2 dopamine receptor gene. , 1992, Biochemistry.

[20]  D. Grandy,et al.  Structure and linkage of the D2 dopamine receptor and neural cell adhesion molecule genes on human chromosome 11q23. , 1992, Genomics.

[21]  S. Cichon,et al.  Systematic screening for mutations in the 5'-regulatory region of the human dopamine D1 receptor (DRD1) gene in patients with schizophrenia and bipolar affective disorder. , 1996, American journal of medical genetics.

[22]  Christer Halldin,et al.  No elevated D2 dopamine receptors in neuroleptic-naive schizophrenic patients revealed by positron emission tomography and [11C]N-methylspiperone , 1995, Psychiatry Research: Neuroimaging.

[23]  K. Blum,et al.  No structural mutation in the dopamine D2 receptor gene in alcoholism or schizophrenia. Analysis using denaturing gradient gel electrophoresis. , 1994, JAMA.

[24]  M. Itokawa,et al.  A structural polymorphism of human dopamine D2 receptor, D2(Ser311-->Cys). , 1993, Biochemical and biophysical research communications.

[25]  N. Craddock,et al.  Association study of bipolar disorder using a functional polymorphism (Ser311→Cys) in the dopamine D2 receptor gene , 1995, Psychiatric genetics.

[26]  J. Lieberman,et al.  No evidence for association of dopamine D2 receptor variant (Ser311/Cys311) with major psychosis. , 1996, American journal of medical genetics.

[27]  M. Nöthen,et al.  Association versus linkage studies in psychosis genetics. , 1993, Journal of medical genetics.