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.
| Original language | English |
|---|---|
| Pages (from-to) | 377-382 |
| Number of pages | 6 |
| Journal | European Journal of Human Genetics |
| Volume | 12 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2004 |
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Keywords
- 5-HTTLPR polymorphism
- Association study
- Bipolar affective disorders
- Candidate genes
- Serotonin neurotransmission
- SLC6A4 gene
- Unipolar affective disorders
ASJC Scopus subject areas
- Genetics(clinical)
Cite this
Serotonin transporter 5HTTLPR polymorphism and affective disorders : No evidence of association in a large European multicentre study. / 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; Jakovljevič, Miro; Ivezič, Sladana; Rietschel, Marcella; Milanova, Vihra; Van Broeckhoven, Christine.
In: European Journal of Human Genetics, Vol. 12, No. 5, 05.2004, p. 377-382.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serotonin transporter 5HTTLPR polymorphism and affective disorders
T2 - No evidence of association in a large European multicentre study
AU - Mendlewicz, Julien
AU - Massat, Isabelle
AU - Souery, Daniel
AU - Del-Favero, Jurgen
AU - Oruč, Lilijana
AU - Nöthen, Markus M.
AU - Blackwood, Douglas
AU - Muir, Walter
AU - Battersby, Sharon
AU - Lerer, Beny
AU - Segman, Ronen H.
AU - Kaneva, Radka
AU - Serretti, Alessandro
AU - Lilli, Roberta
AU - Lorenzi, Christian
AU - Jakovljevič, Miro
AU - Ivezič, Sladana
AU - Rietschel, Marcella
AU - Milanova, Vihra
AU - Van Broeckhoven, Christine
PY - 2004/5
Y1 - 2004/5
N2 - 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.
AB - 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.
KW - 5-HTTLPR polymorphism
KW - Association study
KW - Bipolar affective disorders
KW - Candidate genes
KW - Serotonin neurotransmission
KW - SLC6A4 gene
KW - Unipolar affective disorders
UR - http://www.scopus.com/inward/record.url?scp=2442696545&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2442696545&partnerID=8YFLogxK
U2 - 10.1038/sj.ejhg.5201149
DO - 10.1038/sj.ejhg.5201149
M3 - Article
C2 - 14735161
AN - SCOPUS:2442696545
VL - 12
SP - 377
EP - 382
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 5
ER -