title: Investigation of the human serotonin receptor gene HTR3B in bipolar affective and schizophrenic patients.
abstract: The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) mediates a multitude of central nervous functions by activating 5-HT receptor subtypes. A dysfunction of serotonergic neurotransmission is considered to play a major role in the pathophysiology of complex neuropsychiatric disorders. In our study, a mutation screen of the serotonin receptor gene HTR3B was carried out to explore a putative contribution to the etiology of bipolar affective disorder (BPAD) and schizophrenia (SZ). Screening of 49 patients suffering from BPAD, 78 patients with SZ and 62 control individuals revealed eleven sequence variations including a 3 bp deletion within the 5'UTR (5' untranslated region), four exonic and five intronic SNPs as well as a point mutation in the 3'UTR of HTR3B. Four of these sequence variations have not been described previously. Statistical computation rated most variants as probably non-disease related polymorphisms. However, IVS6 + 31C > T, IVS6 + 40C > A, and 1386T > C were solely detected in bipolar affective patients and in none of the controls. Interestingly, we observed a significant underrepresentation of the 3 bp deletion -100_-102delAAG in an extended sample of 162 bipolar affected patients compared to controls (allele-wise: 8% vs. 15%, P = 0.006, OR = 0.49, 95% CI: 0.3-0.82; genotype-wise: 15,5% vs. 29,0%, P = 0.005, OR = 0.45, 95% CI: 0.26-0.77). We suggest that this deletion may influence translational efficiency, thereby possibly affecting the development of bipolar affective disease.
authors.affiliation: Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Frank
authors.forename: Beate
authors.initials: B
authors.lastname: Niesler
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Helge
authors.initials: H
authors.lastname: Neidt
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Brigitta
authors.initials: B
authors.lastname: Bondy
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Margot
authors.initials: M
authors.lastname: Albus
authors.forename: Gudrun
authors.initials: G
authors.lastname: Rappold
mesh_terms: D020121:5' Untranslated Regions / Q000737:chemistry / Q000235:genetics; D000483:Alleles; D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D020121:5' Untranslated Regions; D044406:Receptors, Serotonin, 5-HT3; D004247:DNA