Association Study of Tyrosine Hydroxylase and Tryptophan Hydroxylase with Schizophrenia / 신경정신의학

ABSTRACT

Neurochemical investigation has played a major role in the search for the cause of schizophrenia. Among many hypotheses, dopamine hypothesis of schizophrenia prevails despite much criticism and qualification. Recently, evidences showing the atypical antipsychotics act via serotonergic mechanism suggest serotonin system as an etiologic factor for schizophrenia. We examined the possibility of the association of enzymes critical for the synthesis of serotonin (tryptophan hydroxylase, TPH) and dopamine (tyrosine hydroxylase, TH) with schizophrenia. The regions of DNA that has been known to be polymorphic were amplified using polymerase chain reaction from the peripheral blood cells of 374 biologically unrelated schizophrenic patients and 393 healthy controls. RFLP (A218C) and VNTR polymorphism (intron 1) were examined for TPH and TH, respectively. The patterns of polymorphisms and the frequencies of each allele were not significantly different between the control and the patient groups, suggesting no possible associations of the genetic polymorphisms of TPH and TH genes and schizophrenia. However, in schizophrenics, the frequency of A type allele was significantly higher in positive group than negative group. Thess findings suggest the association of positive schizophrenia with A type allele of TH gene.