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 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.
Mendlewicz
Julien
J
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, 808 route de Lennik, Belgium. jmendlew@ulb.ac.be
Massat
Isabelle
I
Souery
Daniel
D
Del-Favero
Jurgen
J
Oruc
Lilijana
L
Nöthen
Markus M
MM
Blackwood
Douglas
D
Muir
Walter
W
Battersby
Sharon
S
Lerer
Beny
B
Segman
Ronen H
RH
Kaneva
Radka
R
Serretti
Alessandro
A
Lilli
Roberta
R
Lorenzi
Christian
C
Jakovljevic
Miro
M
Ivezic
Sladana
S
Rietschel
Marcella
M
Milanova
Vihra
V
Van Broeckhoven
Christine
C
D001714:Bipolar Disorder / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics / Q000473:pathology; D005060:Europe; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D013223:Statistics as Topic
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins