Replication of Functional Serotonin Receptor Type 3A and B Variants in Bipolar Affective Disorder: A European Multicenter Study

DSpace/Manakin Repository

Replication of Functional Serotonin Receptor Type 3A and B Variants in Bipolar Affective Disorder: A European Multicenter Study

Show simple item record

dc.contributor.author Hammer, C
dc.contributor.author Cichon, S
dc.contributor.author Mühleisen, T W
dc.contributor.author Haenisch, B
dc.contributor.author Degenhardt, F
dc.contributor.author Breuer, R
dc.contributor.author Witt, S H
dc.contributor.author Strohmaier, J
dc.contributor.author Oruc, L
dc.contributor.author Rivas, F
dc.contributor.author Babadjanova, G
dc.contributor.author Grigoroiu-Serbanescu, M
dc.contributor.author Röth, R
dc.contributor.author Rappold, G
dc.contributor.author Rietschel, M
dc.contributor.author Nöthen, M M
dc.contributor.author Niesler, B
dc.contributor.author Mattheisen, Manuel
dc.contributor.author Hauser, J
dc.date.accessioned 2012-10-22T17:07:10Z
dc.date.issued 2012
dc.identifier.citation Hammer, C, S Cichon, T W Mühleisen, B Haenisch, F Degenhardt, M Mattheisen, R Breuer, et al. 2012. Replication of functional serotonin receptor type 3A and B variants in bipolar affective disorder: A European Multicenter Study. Translational Psychiatry 2(4): e103. en_US
dc.identifier.issn 2158-3188 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:9793861
dc.description.abstract Serotonin type 3 receptors (\(5-HT_3\)) are involved in learning, cognition and emotion, and have been implicated in various psychiatric phenotypes. However, their contribution to the pathomechanism of these disorders remains elusive. Three single nucleotide polymorphisms (SNPs) in the \(HTR3A\) and \(HTR3B\) genes (rs1062613, rs1176744 and rs3831455) have been associated with bipolar affective disorder (BPAD) in pilot studies, and all of them are of functional relevance. We performed a European multicenter study to confirm previous results and provide further evidence for the relevance of these SNPs to the etiology of neuropsychiatric disorders. This involved analysis of the distribution of the three SNPs among 1804 BPAD cases and 2407 healthy controls. A meta-analysis revealed a pooled odds ratio of 0.881 (P=0.009, 95% confidence intervals=0.802–0.968) for the non-synonymous functional SNP \(HTR3B\) p.Y129S (rs1176744), thereby confirming previous findings. In line with this, the three genome-wide association study samples BOMA (Bonn-Mannheim)-BPAD, WTCCC (Wellcome Trust Case Control Consortium)-BPAD and GAIN (Genetic Association Information Network)-BPAD, including >3500 patients and 5200 controls in total, showed an overrepresentation of the p.Y129 in patients. Remarkably, the meta-analysis revealed a P-value of 0.048 (OR=0.934, fixed effect model). We also performed expression analyses to gain further insights into the distribution of \(HTR3A\) and \(HTR3B\) mRNA in the human brain. \(HTR3A\) and \(HTR3B\) were detected in all investigated brain tissues with the exception of the cerebellum, and large differences in the A:B subunit ratio were observed. Interestingly, expression of the B subunit was most prominent in the brain stem, amygdalae and frontal cortex, regions of relevance to psychiatric disorders. In conclusion, the present study provides further evidence for the presence of impaired \(5-HT_3\) receptor function in BPAD. en_US
dc.language.iso en_US en_US
dc.publisher Nature Publishing Group en_US
dc.relation.isversionof doi:10.1038/tp.2012.30 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337070/pdf/ en_US
dash.license LAA
dc.subject association en_US
dc.subject bipolar en_US
dc.subject BPAD en_US
dc.subject HTR3 en_US
dc.subject HTR3B en_US
dc.subject 5-HT3 en_US
dc.title Replication of Functional Serotonin Receptor Type 3A and B Variants in Bipolar Affective Disorder: A European Multicenter Study en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Translational Psychiatry en_US
dash.depositing.author Mattheisen, Manuel
dc.date.available 2012-10-22T17:07:10Z

Files in this item

Files Size Format View
3337070.pdf 429.1Kb PDF View/Open

This item appears in the following Collection(s)

Show simple item record

 
 

Search DASH


Advanced Search
 
 

Submitters