A FUNCTIONAL POLYMORPHISM IN THE PROMOTER REGION OF THE DOPAMINE D2 RECEPTOR GENE IS ASSOCIATED WITH SCHIZOPHRENIA

An excess dopaminergic activity may be implicated in the etiology of s chizophrenia. Our objective was to identify nucleotide variants in the 5' region of the dopamine D2 receptor gene (DRD2) and to clarify thei r effects on schizophrenia. We identified two polymorphisms, the A-241 G and -141C Ins/Del, by examination of 259 bp in the 5'-flanking regio n and 249 bp of exon 1 of DRD2, Reporter constructs containing the -14 1C Del allele cloned into a luciferase reporter plasmid drove 21% (Y-7 9 cells) and 43% (293 cells) expression compared with the -141C Ins al lele, In a case-control study, the -141C Del allele frequency was sign ificantly lower in 260 schizophrenic patients than in 312 controls (OR = 0.60, 95% CI 0.44-0.81, P<0,001), No significant association was fo und between the A-241G polymorphism and in vitro luciferase activity, or in allele frequency between the patients versus controls, These fin dings show that the -141C Ins/Del may be a functional polymorphism in the 5'-promoter region of DRD2 and may affect the susceptibility to sc hizophrenia.