Study Report

Reference	Niesler, B.,2001(b) PMID: 11207027
Citation	Niesler, B., B. Weiss, et al. (2001). "Serotonin receptor gene HTR3A variants in schizophrenic and bipolar affective patients." Pharmacogenetics 11(1): 21-27.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	70 schizophrenic patients, 48 patients with bipolar affective disorder and 47 healthy control persons
SNP/Region/Marker Size	11 variants
Predominant Ethnicity	Caucasian
Population	German

Sample Diagnosis	DSM
Sample Status	The screening sample included 70 patients with schizophrenia, 48 patients with bipolar affective disorder, and 47 control subjects for whom all exons of HTR3A were analysed. The screening sample differed slightly between exons, e.g. 70+-76 patients with schizophrenia, 48 or 49 patients with bipolar affective disorder and 47 or 48 control subjects were screened for individual exons. All schizophrenic and 36 bipolar patients were derived from affected sib pairs and multiple affected pedigrees chosen at random prior to genotyping. The remaining bipolar patients as well as the patients from the extended samples were recruited from inpatient and day hospital facilities. The extended schizophrenic sample consisted of an additional 205 patients for exon 8 (total 75 + 205 =280) and 282 patients for exon 9 (total 76+282=358). The same screening sample was previously used for investigation of other serotonin receptor genes (Erdmann et al., 1995; Shimron-Abarbanell et al., 1995; Erdmann et al., 1996a,b; Shimron-Abarbanell et al., 1996). All patients were unrelated and of German descent. The control subjects from the screening sample were derived from CEPH families (Dausset et al., 1990). The extended control sample consisted of anonymous blood donors for whom only ethnicity, year of birth and sex were known.
Technique	PCR and SSCP analysis
Statistical Method	chi-square tests
Result Summary	We discovered six sequence variants, five of which represent polymorphisms. These polymorphisms could not be associated with schizophrenia and bipolar affective disorder (P = 0.055-1). We also detected a missense mutation in exon 9 in a schizophrenic patient at a conserved position (Pro391Arg). To determine the incidence of this substitution an extended set of 358 schizophrenic patients and 155 control individuals was investigated. The Pro391Arg mutation was not detected in these schizophrenic patients and controls screened. However, a second missense mutation (Arg344His) was detected in one schizophrenic patient, but not in any of the controls. These results suggest that the observed mutations in HTR3A are rare and therefore do not play a major role in the aetiology of the disorder. Further studies are needed to support the hypothesis that HTR3A may contribute to the schizophrenia in these patients.