Association between brain-derived neurotrophic factor gene and a severe form of bipolar disorder, but no interaction with the serotonin transporter gene.
BACKGROUND
Recent data suggest that brain-derived neurotrophic factor (BDNF) and the serotonergic system are involved and interact in major depressive disorder and suicidal behavior (SB). Several family and population-based studies have reported associations between the BDNF gene and serotonin-related genes, specifically the serotonin transporter (5HTT) gene, with bipolar disorder (BD) and SB. However, despite the fact that gene-by-gene interaction between BDNF and 5HTT has been demonstrated in monoamine deficiencies in animals, this kind of interaction has never been tested in humans. Our hypothesis is that some BDNF and 5HTT polymorphisms might confer increased risk for BD and SB and that both genes may interact with each other.


METHODS
To test this hypothesis, we genotyped the most common BDNF polymorphisms, G196A (Val66Met), A-633T and BDNF-LCPR, as well as 5HTT (5HTT-LPR), in 447 BD patients and 370 controls.


RESULTS
We replicated the association previously reported between BDNF G196A (Val66Met) polymorphism and BD. We also observed a correlation between the number of G196 alleles and short alleles of 5HTT-LPR and the severity of SB in BD. However, we found no significant interaction between these two markers.


CONCLUSIONS
These results suggest that BDNF G196A as well as 5HTT-LPR polymorphisms confer risk for SB in BD, but we did not observe any evidence for an interaction between them.
Vincze
Ilona
I
Department of Psychiatry, University Hospital of Geneva, Geneva, Switzerland.
Perroud
Nader
N
Buresi
Catherine
C
Baud
Patrick
P
Bellivier
Frank
F
Etain
Bruno
B
Fournier
Claire
C
Karege
Felicien
F
Matthey
Marie-Louise
ML
Preisig
Martin
M
Leboyer
Marion
M
Malafosse
Alain
A
D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004198:Disease Susceptibility; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013406:Suicide, Attempted / Q000523:psychology*
D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins