Replication of functional serotonin receptor type 3A and B variants in bipolar affective disorder: a European multicenter study

被引：39

作者：

Hammer, C. ^{[1
]}

Cichon, S. ^{[2
,3
,4
]}

Muehleisen, T. W. ^{[2
,4
]}

Haenisch, B. ^{[2
,4
]}

Degenhardt, F. ^{[2
,4
]}

Mattheisen, M. ^{[2
,4
,5
,6
,7
]}

Breuer, R. ^{[8
]}

Witt, S. H. ^{[8
]}

Strohmaier, J. ^{[8
]}

Oruc, L. ^{[9
]}

Rivas, F. ^{[10
]}

Babadjanova, G. ^{[11
]}

Grigoroiu-Serbanescu, M. ^{[12
]}

Hauser, J. ^{[13
]}

Roeth, R. ^{[1
,14
]}

Rappold, G. ^{[1
]}

Rietschel, M. ^{[8
]}

Noethen, M. M. ^{[2
,4
,15
]}

Niesler, B. ^{[1
,14
]}

机构：

[1] Heidelberg Univ, Dept Human Mol Genet, D-69120 Heidelberg, Germany

[2] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany

[3] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany

[4] Univ Bonn, Inst Human Genet, Bonn, Germany

[5] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[6] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Boston, MA USA

[8] Univ Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany

[9] Univ Sarajevo, Ctr Clin, Psychiat Clin, Sarajevo 71000, Bosnia & Herceg

[10] Civil Hosp Carlos Haya, Malaga, Spain

[11] Russian State Med Univ, Moscow 117437, Russia

[12] Alexandru Obregia Clin Psychiat Hosp, Biometr Psychiat Genet Res Unit, Bucharest, Romania

[13] Lab Psychiat Genet, Dept Psychiat, Poznan, Poland

[14] Heidelberg Univ, Inst Human Genet, nCounter Core Facil, Heidelberg, Germany

[15] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

来源：

TRANSLATIONAL PSYCHIATRY | 2012年 / 2卷

基金：

英国惠康基金;

关键词：

association; bipolar; BPAD; HTR3; HTR3B; 5-HT3; 5-HT3; RECEPTOR; GENE HTR3A; ASSOCIATION; EXPRESSION; REGION; DELETION; CLONING; HETEROGENEITY; POLYMORPHISM; DEPRESSION;

D O I：

10.1038/tp.2012.30

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Serotonin type 3 receptors (5-HT3) 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 43500 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-HT3 receptor function in BPAD. Translational Psychiatry (2012) 2, e103; doi:10.1038/tp.2012.30; published online 17 April 2012

引用

页码：e103 / e103

页数：8

共 45 条

[1] PHARMACOLOGICAL AND REGIONAL CHARACTERIZATION OF [H-3] LY278584 BINDING-SITES IN HUMAN BRAIN [J].

ABI-DARGHAM, A ;

LARUELLE, M ;

WONG, DT ;

ROBERTSON, DW ;

WEINBERGER, DR ;

KLEINMAN, JE .

JOURNAL OF NEUROCHEMISTRY, 1993, 60 (02) :730-737

[2] IDENTIFICATION AND CHARACTERIZATION OF 5-HYDROXYTRYPTAMINE3 RECOGNITION SITES IN HUMAN-BRAIN TISSUE [J].

BARNES, JM ;

BARNES, NM ;

COSTALL, B ;

IRONSIDE, JW ;

NAYLOR, RJ .

JOURNAL OF NEUROCHEMISTRY, 1989, 53 (06) :1787-1793

[3] The 5-HT3 receptor - the relationship between structure and function [J].

Barnes, Nicholas M. ;

Hales, Tim G. ;

Lummis, Sarah C. R. ;

Peters, John A. .

NEUROPHARMACOLOGY, 2009, 56 (01) :273-284

[4]

Belelli D, 1995, MOL PHARMACOL, V48, P1054

[5] Pituitary-adrenal activity in acute and chronically stressed male and female mice lacking the 5-HT-3A receptor [J].

Bhatnagar, S ;

Vining, C .

STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, 2004, 7 (04) :251-256

[6] Deletion of the 5-HT3 receptor differentially affects behavior of males and females in the Porsolt forced swim and defensive withdrawal tests [J].

Bhatnagar, S ;

Nowak, N ;

Babich, L ;

Bok, L .

BEHAVIOURAL BRAIN RESEARCH, 2004, 153 (02) :527-535

[7] DISTRIBUTION AND CHARACTERIZATION OF THE [H-3] GRANISETRON-LABELED 5-HT3 RECEPTOR IN THE HUMAN FOREBRAIN [J].

BUFTON, KE ;

STEWARD, LJ ;

BARBER, PC ;

BARNES, NM .

NEUROPHARMACOLOGY, 1993, 32 (12) :1325-1331

[8] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[9] The minicolumn hypothesis in neuroscience [J].

Buxhoeveden, DP ;

Casanova, MF .

BRAIN, 2002, 125 :935-951

[10] The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons [J].

Chameau, Pascal ;

Inta, Dragos ;

Vitalis, Tania ;

Monyer, Hannah ;

Wadman, Wytse J. ;

van Hooft, Johannes A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (17) :7227-7232

← 1 2 3 4 5 →