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Mol Psychiatry. 2001 Mar;6(2):217-9.

Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia.

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  • 1Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.


Several different lines of evidence suggest that genes involved in serotonergic neurotransmission are factors in the pathogenesis of schizophrenia. For example, 5-HT(5A) knockout mice revealed decreased locomotor response to lysergic diethylamide (LSD), which produces a psychotic-like state in healthy people. Recently, we reported a naturally occurring conservative Pro15Ser substitution in the 5-HT(5A) receptor. Here, we evaluate whether this substitution is associated with schizophrenia in a sample including 249 unrelated Japanese schizophrenia patients and 253 unrelated controls. Patients and controls were genotyped for the Pro15Ser polymorphism by a PCR-RFLP assay. Ser15 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 stratification, this finding is preliminary pending further studies, including studies using the transmission/disequilibrium test to eliminate stratification bias or control loci to assess ethnic matching of cases and controls.

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