title: Identification of a naturally occurring polymorphism in the promoter region of the norepinephrine transporter and analysis in major depression.
abstract: Disturbances in the noradrenergic neurotransmission system have been implicated in the etiology of mood disorders. The norepinephrine transporter (NET) is a main target of antidepressant action and was shown to be dysregulated in major depression. Despite the clinical and physiological significance of NET gene regulation, little is known about the transcriptional control mechanisms governing its expression. Since it is well established that affective disorders have a genetic component with many genes of small effect contributing to the genetic susceptibility of depression, the NET gene is an interesting candidate gene for affective disorders. In a search for polymorphisms or mutations in the 5' flanging region of the NET gene we sequenced approximately 1000 bp upstream of the first codon in the NET gene promoter in 100 patients with major depression and 100 healthy controls. We identified a so far unknown T --> C polymorphism 182 bp upstream of the start codon in a transcriptional relevant region. In a case control association study we investigated the newly identified T-182C polymorphism and an already known G1287A polymorphism in exon 9 of the NET gene in a sample of 193 patients with major depression and 136 healthy, non-related controls. No statistical significant differences between patients and controls were found for any of the analyzed polymorphisms, either in the genotype distribution or in the allele frequencies. Our results suggest that the investigated polymorphisms are not major susceptibility factors in the etiology of major depression.
authors.affiliation: Psychiatric Hospital of the Ludwig-Maximilians-University Munich, Nussbaumstr. 7, D-80336 Munich, Germany. Peter.Zill@psu.med.uni-muenchen.de
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
authors.forename: Rolf
authors.initials: R
authors.lastname: Engel
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Baghai
authors.forename: Georg
authors.initials: G
authors.lastname: Juckel
authors.forename: Thomas
authors.initials: T
authors.lastname: Frodl
authors.forename: Florian
authors.initials: F
authors.lastname: Müller-Siecheneder
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
authors.forename: Cornelius
authors.initials: C
authors.lastname: Schüle
authors.forename: Christo
authors.initials: C
authors.lastname: Minov
authors.forename: Stefanie
authors.initials: S
authors.lastname: Behrens
authors.forename: Rainer
authors.initials: R
authors.lastname: Rupprecht
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hegerl
authors.forename: Hans Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.forename: Brigitta
authors.initials: B
authors.lastname: Bondy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics; D004247:DNA / Q000235:genetics; D003866:Depressive Disorder / Q000209:etiology / Q000235:genetics* / Q000523:psychology; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D027981:Symporters / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D003062:Codon; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D027981:Symporters; D004247:DNA