title: Association of major depression with rare functional variants in norepinephrine transporter and serotonin1A receptor genes.
abstract: Dysregulations of central noradrenergic and serotonergic neurotransmission have been suggested to contribute to the pathogenesis of neuropsychiatric disorders such as depression. The norepinephrine transporter (NET; SLC6A2) and the serotonin (5-HT)(1A) receptor (5-HT(1A) receptor; HTR1A) play an important role in central nervous monoaminergic homeostasis. As shown previously, variations in the human NET and 5-HT(1A) receptor genes can alter noradrenergic and serotonergic signaling in the brain: a single nucleotide polymorphism (SNP) in the coding region of the NET gene resulting in a F528C substitution increased plasma membrane expression of this NET variant, and a SNP in the human 5-HT(1A) receptor gene leading to the R219L receptor variant almost abolished cellular signal transduction subsequent to receptor activation. The present study aimed at investigating whether these NET and 5-HT(1A) receptor variants are associated with major depression (MD). The sample comprised 426 patients suffering from unipolar MD as well as 643 healthy control subjects for the variants of the 5-HT(1A) receptor and the NET. Both SNPs were shown to be associated with MD. In conclusion, our results favor the hypothesis that monoaminergic neurotransmission in general and the F528C NET and R219L 5-HT(1A) receptor variants in particular are involved in the pathogenesis of depression.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Bonn, Bonn, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Haenisch
authors.forename: Karoline
authors.initials: K
authors.lastname: Linsel
authors.forename: Michael
authors.initials: M
authors.lastname: Brüss
authors.forename: Ralf
authors.initials: R
authors.lastname: Gilsbach
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Rolf
authors.initials: R
authors.lastname: Fimmers
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Astrid
authors.initials: A
authors.lastname: Zobel
authors.forename: Susanne
authors.initials: S
authors.lastname: Höfels
authors.forename: Vera
authors.initials: V
authors.lastname: Guttenthaler
authors.forename: Manfred
authors.initials: M
authors.lastname: Göthert
authors.forename: Heinz
authors.initials: H
authors.lastname: Bönisch
mesh_terms: D017677:Age Distribution; D017668:Age of Onset; D016022:Case-Control Studies; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A