Parent of origin effect and differential allelic expression of BDNF Val66Met in suicidal behaviour.
OBJECTIVE
Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of mood disorders and may also be involved in suicidal behaviour since BDNF levels are decreased in brain and plasma of suicide victims. Because the differential allelic expression of Val66Met BDNF gene on suicidal behaviour has not been investigated, we analyzed the parent-of-origin effect (POE) in suicide attempters and the differential expression of BDNF Val66Met alleles in suicide victims.


METHODS
We performed a family-based association study and ETDT analyses of the Val66Met polymorphism in nuclear families with at least one subject affected by major psychosis with suicidal behaviour, and compared allele-specific mRNA levels in post-mortem brain samples from suicide and non-suicide victims. The subjects included in this study have diagnosis of schizophrenia, bipolar disorder type I and type II.


RESULTS
Allele 3 in the GT repeat polymorphism was transmitted significantly more often to patients who attempted suicide (maternal transmissions: 46/22, P = 0.003; paternal transmissions: 55/30, P = 0.006). There was no significant difference between maternal and paternal transmission ratios. Furthermore, there was no significant difference in the ratio of Val/Met-specific mRNA expression between suicide victims and controls.


CONCLUSIONS
These data do not support a role for allelic imbalance or POE of BDNF for suicidal behaviour in major psychoses.
de Luca
Vincenzo
V
Department of Psychiatry, University of Toronto, Toronto, Canada.
Souza
Renan P
RP
Zai
Clement C
CC
Panariello
Fabio
F
Javaid
Naima
N
Strauss
John
J
Kennedy
James L
JL
Tallerico
Teresa
T
Wong
Albert H
AH
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D010290:Parents; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics; D013405:Suicide; D013406:Suicide, Attempted; D014633:Valine / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D008715:Methionine; D014633:Valine