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- Title
Serotonin transporter 5HTTLPR polymorphism and affective disorders: no evidence of association in a large European multicenter study.
- Authors
Mendlewicz, Julien; Massat, Isabelle; Souery, Daniel; Del-Favero, Jurgen; Oruč, Lilijana; Nöthen, Markus M.; Blackwood, Douglas; Muir, Walter; Battersby, Sharon; Lerer, Beny; Segman, Ronen H.; Kaneva, Radka; Serretti, Alessandro; Lilli, Roberta; Lorenzi, Christian; Jacovljevič, Miro; Ivezič, Sladana; Rietschel, Marcella; Milanova, Vihra
- Abstract
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.European Journal of Human Genetics (2004) 12, 377-382. doi:10.1038/sj.ejhg.5201149 Published online 21 January 2004
- Subjects
AFFECTIVE disorders; SEROTONIN; GENETIC transcription; GENETIC polymorphisms; PATHOLOGICAL psychology; HUMAN genetics; MENTAL illness risk factors
- Publication
European Journal of Human Genetics, 2004, Vol 12, Issue 5, p377
- ISSN
1018-4813
- Publication type
Article
- DOI
10.1038/sj.ejhg.5201149