Association of a 5-MT5A receptor polymorphism, Pro15Ser, to schizophrenia

Several different lines of evidence suggest that genes involved in serotone rgic neurotransmission are factors in the pathogenesis of schizophrenia. Fo r example, 5-HT5A knockout mice revealed decreased locomotor response to ly sergic diethylamide (LSD), which produces a psychotic-like state in healthy people. Recently, we reported a naturally occurring conservative Pro15Ser substitution in the 5-HT5A receptor. Here, we evaluate whether this substit ution is associated with schizophrenia in a sample including 249 unrelated Japanese schizophrenia patients and 253 unrelated controls. Patients and co ntrols were genotyped for the Pro15Ser polymorphism by a PCR-RFLP assay. Se r15 allele frequencies were 0.07 in patients with schizophrenia and 0.02 in controls (chi (2) = 17.42, df =1, P < 0.0001), Thus, We detected a highly significant association of Pro15Ser to schizophrenia in a large population of Japanese schizophrenia patients and controls, Since case-control studies have an inherent potential for false-positive results due to population st ratification, this finding is preliminary pending further studies, includin g studies using the transmission/disequilibrium test to eliminate stratific ation bias or control loci to assess ethnic matching of cases and controls.