Association of major depression with rare functional variants in norepinephrine transporter and serotonin1A receptor genes.
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.
Haenisch
Britta
B
Institute of Pharmacology and Toxicology, University of Bonn, Bonn, Germany.
Linsel
Karoline
K
Brüss
Michael
M
Gilsbach
Ralf
R
Propping
Peter
P
Nöthen
Markus M
MM
Rietschel
Marcella
M
Fimmers
Rolf
R
Maier
Wolfgang
W
Zobel
Astrid
A
Höfels
Susanne
S
Guttenthaler
Vera
V
Göthert
Manfred
M
Bönisch
Heinz
H
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*
D050484:Norepinephrine Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A