Serotonin transporter 5HTTLPR polymorphism and affective disorders: no evidence of association in a large European multicenter study

The available data from preclinical and pharmacological studies on the role of the serotonin transporter (5-HTT) support the hypothesis that a dysfunction in brain serotonergic system activity contributes to the vulnerability to affective disorders (AD). 5-HTT is the major site of serotonin reuptake...

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Published in:	European journal of human genetics : EJHG Vol. 12; no. 5; pp. 377 - 382
Main Authors:	MENDLEWICZ, Julien, MASSAT, Isabelle, SEGMAN, Ronen H, KANEVA, Radka, SERRETTI, Alessandro, LILLI, Roberta, LORENZI, Christian, JAKOVLJEVIC, Miro, IVEZIC, Sladana, RIETSCHEL, Marcella, MILANOVA, Vihra, VAN BROECKHOVEN, Christine, SOUERY, Daniel, DEL-FAVERO, Jurgen, ORUC, Lilijana, NÖTHEN, Markus M, BLACKWOOD, Douglas, MUIR, Walter, BATTERSBY, Sharon, LERER, Beny
Format:	Journal Article
Language:	English
Published:	Avenel, NJ Nature Publishing 01-05-2004 Nature Publishing Group
Subjects:	Biological and medical sciences Bipolar Disorder - genetics Bipolar Disorder - pathology Carrier Proteins - genetics Depressive Disorder - genetics Depressive Disorder - pathology Europe Female Gene Frequency General aspects. Genetic counseling Genotype Humans Male Medical genetics Medical sciences Membrane Glycoproteins - genetics Membrane Transport Proteins Middle Aged Mood Disorders - genetics Mood Disorders - pathology Nerve Tissue Proteins - genetics Polymorphism, Genetic Serotonin Plasma Membrane Transport Proteins Statistics as Topic Europe Affective disorder Mood disorder Association Serotonin Nitric oxide Multicenter study European Polymorphism
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Summary:	The available data from preclinical and pharmacological studies on the role of the serotonin transporter (5-HTT) support the hypothesis that a dysfunction in brain serotonergic system activity contributes to the vulnerability to affective disorders (AD). 5-HTT is the major site of serotonin reuptake into the presynaptic neuron, and it has been shown that the polymorphic repeat polymorphism in the 5-HTT promotor region (5-HTTLPR) may affect gene-transcription activity. 5-HTT maps to chromosome 17 at position 17q11.17-q12, and the 5-HTTLPR polymorphisms have been extensively investigated in AD with conflicting results. The present study tested the genetic contribution of the 5-HTTLPR polymorphism in a large European multicenter case-control sample, including 539 unipolar (UPAD), 572 bipolar patients (BPAD), and 821 controls (C). Our European collaboration has led to efforts to optimize a methodology that attenuates some of the major limitations of the case-control association approach. No association was found with primary psychiatric diagnosis (UPAD and BPAD) and with phenotypic traits (family history of AD, suicidal attempt, and presence of psychotic features). Our negative findings are not attributable to the lack of statistical power, and may contribute to clarify the role of 5-HTTLPR polymorphism in AD.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1018-4813 1476-5438
DOI:	10.1038/sj.ejhg.5201149