DOPAMINE D4 RECEPTOR VARIANT, D4GLYCINE194, IN AFRICANS, BUT NOT IN CAUCASIANS - NO ASSOCIATION WITH SCHIZOPHRENIA

Because antipsychotic drugs selectively block dopamine receptors and s ince dopamine D4 receptors are elevated sixfold in postmortem schizoph renia brain, we searched for possible abnormalities in the coding regi on of the genomic DNA sequence for the dopamine D4 receptor in control and schizophrenia tissues. The DNA sequence for the first 250 bases o f exon 3 of this receptor was examined in the genomic DNA from 296 con trol individuals and 58 schizophrenics. Twenty-three out of 183 contro l 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 glyci ne at amino acid position 194. The identical prevalence of 12.5% indic ates that the variant is not associated with schizophrenia. The amino acid replacement occurs one amino acid away from a serine amino acid w hich is critical for the attachment of dopamine. None of the 147 Cauca sians (113 controls; 34 schizophrenics) revealed this variant, termed D4GLYCINE194. (C) 1994 Wiley-Liss, Inc.