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Genes that regulate serotonergic (5-HT) systems may underlie the etiology of schizophrenia. In this study the gene encoding the 5-HT2A receptor in schizophrenics and healthy controls was examined. First, we sequenced all exons and the flanking introns of the 5-HT2A receptor gene in 10 schizophrenics and 10 controls. The substitution of C for T at position 102 in exon, which had been reported by Warren et al. (1993), was confirmed. Restriction fragment length polymorphism (RFLP) analysis revealed no association between polymorphism and schizophrenia. There was no association between the polymorphism and subdiagnosis, family history, age of onset, amounts of antipsychotics, or positive and negative symptoms before or after medication. Other polymorphisms in the gene were screened in 100 schizophrenics by the single-strand conformation polymorphism method, but none was found. Our results suggest that an abnormality in the 5-HT2A receptor gene in schizophrenia is unlikely.

We studied the 5'-flanking promoter region comprising positions -1441 to +128 of the 5-HT2A receptor gene in 95 schizophrenics and 100 unrelated normal control subjects. The genes encoding the 5-HT2A receptor exons and the adjoining introl regions had already been studied in these subjects, but no disease specific polymorphism was found (Ishigaki et al., 1996). The DNA fragments were amplified by means of the polymerase chain reaction (PCR), and then analyzed by the single-stranded conformation polymorphism (SSCP) and sequencing methods. One patient had a substitution, from A to G, at position -668, and a 5 nucleotide deletion of TACTT at positions -646 to -642, however, the patient also had a normal sequence on the other allele. SSCP analysis showed that the other schizophrenics and the control subjects did not have any polymorphism in the 5'-flanking promoter region of the 5-HT2A receptor gene.