Serotonin receptor gene HTR3A variants in schizophrenic and bipolar affective patients

Serotonin receptor genes have always been considered excellent candidate ge nes in the aetiology of neurogenetic diseases, In this study, we assessed s equence variations of the HTR3A gene. For this purpose, we established exon - specific primers and analysed DNA samples from 165 unrelated individuals including 70 schizophrenic patients, 48 patients with bipolar affective dis order and 47 healthy control persons using polymerase chain reaction/single -strand conformational polymorphism analysis. We discovered six sequence va riants, five of which represent polymorphisms. These polymorphisms could no t be associated with schizophrenia and bipolar affective disorder (P = 0.05 5-1). We also detected a missense mutation in exon 9 in a schizophrenic pat ient at a conserved position (Pro(391)Arg). To determine the incidence of t his substitution an extended set of 358 schizophrenic patients and 155 cont rol individuals was investigated, The Pro(391)Arg mutation was not detected in these schizophrenic patients and controls screened. However, a second m issense mutation (Arg(344)His) was detected in one schizophrenic patient, b ut not in any of the controls, These results suggest that the observed muta tions in HTR3A are rare and therefore do not play a major role in the aetio logy of the disorder. Further studies are needed to support the hypothesis that HTR3A may contribute to the schizophrenia in these patients. Pharmacog enetics 11:21-27 (C) 2001 Lippincott Williams & Wilkins.