Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians: no association with schizophrenia.
Because antipsychotic drugs selectively block dopamine receptors and since dopamine D4 receptors are elevated sixfold in postmortem schizophrenia brain, we searched for possible abnormalities in the coding region of the genomic DNA sequence for the dopamine D4 receptor in control and schizophrenia tissues. The DNA sequence for the first 250 bases of exon 3 of this receptor was examined in the genomic DNA from 296 control individuals and 58 schizophrenics. Twenty-three out of 183 control blacks (12.6%) and 3 out of 24 (12.5%) schizophrenic blacks revealed a replacement of T by G, predicting a substitution of valine by glycine at amino acid position 194. The identical prevalence of 12.5% indicates that the variant is not associated with schizophrenia. The amino acid replacement occurs one amino acid away from a serine amino acid which is critical for the attachment of dopamine. None of the 147 Caucasians (113 controls; 34 schizophrenics) revealed this variant, termed D4GLYCINE194.
Seeman
P
P
Department of Pharmacology, Clarke Institute of Psychiatry, Toronto, Canada.
Ulpian
C
C
Chouinard
G
G
Van Tol
H H
HH
Dwosh
H
H
Lieberman
J A
JA
Siminovitch
K
K
Liu
I S
IS
Waye
J
J
Voruganti
P
P
D000328:Adult; D000349:Africa / Q000208:ethnology; D000595:Amino Acid Sequence; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D001921:Brain / Q000378:metabolism; D004247:DNA / Q000032:analysis / Q000235:genetics; D005091:Exons; D005260:Female; D014644:Genetic Variation; D005998:Glycine; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D015995:Prevalence; D017433:Protein Structure, Secondary; D011954:Receptors, Dopamine / Q000737:chemistry / Q000235:genetics*; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D012091:Repetitive Sequences, Nucleic Acid; D012559:Schizophrenia / Q000235:genetics*; D044465:White People / Q000235:genetics*
C493599:DRD4 protein, human; D009838:Oligodeoxyribonucleotides; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D004247:DNA; D005998:Glycine