Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene in schizophrenia.

Several studies have suggested that the transcriptional activity of the DRD4 gene may exert an important role in susceptibility to schizophrenia. To address this issue, we studied the association of schizophrenia and polymorphisms including -616C>G, -603T>del, -602G>del, 600G>C, -521C>T, -376C>T and a 120 bp tandem duplication polymorphism (120 bp repeat) in 1.2 kb upstream from the initiation codon in the promoter region of the DRD4 gene with 210 schizophrenic cases and 206 healthy controls. The results showed a significant excess of allele L of the 120 bp repeat in the schizophrenic patients compared to the controls (X(2)=8.585, df=1, P=0.003, OR=1.546, 95% CI=1.154-2.070). No significant difference was detected in the frequencies of genotype and allele of six other polymorphisms between the two groups. However, haplotypic distribution of 120 bp repeat, -616C>G, -602G>del, -521C>T and -376C>T was significantly different between case and control groups (P=0.005). This might cause the alteration of the transcriptional regulation of the DRD4 gene, as the consensus sequences of binding sites for several known transcription factors are involved in this region.