ISSN 10227954, Russian Journal of Genetics, 2013, Vol. 49, No. 12, pp. 1250–1253. © Pleiades Publishing, Inc., 2013.
Original Russian Text © Z.G. Kokaeva, T.O. Kochetkova, E.V. Afonchikova, N.S. Kondratyeva, E.A. Klimov, 2013, published in Genetika, 2013, Vol. 49, No. 12, pp. 1432–1435.
Brainderived neurotrophic factor (BDNF)
belongs to superfamily of closely related peptides—
neurotrophins that play important role in establish
ment of plasticity in mature nervous system: they pro
vide growth, development, and survival in neuronal
populations. Particularly, BDNF participates in sur
vival and differentiation of dopaminergic neurons,
appears to be the trophic factor for serotoninergic
neurons, and plays important role in synapse forma
tion. Proteins of this family are synthesized as pre
forms which can be cleaved intracellularly, forming
mature secreted ligands. Mature neurotrophins selec
tively bind to tyrosine kinase receptors which activate
signaling pathways leading to differentiation or sur
vival of neurons .
It is known that
gene is localized in chromo
some 11 locus p14.1 and has complex structure:
9 functional promoters and 11 exons. The sequence
encoding functional part of the protein is in the last
exon. Alternative promoters provide nine tissue and
timespecific transcripts that encode inter alia differ
ent leading sequences of preproprotein BDNF .
The gene is expressed in nociceptive sensory neurons
and modulates functioning of metabotropic and iono
tropic receptors of glutamate.
Single nucleotide polymorphisms (SNPs) in
gene in different populations were found to be associ
ated with disorders generally common in big cities,
such as autism , Alzheimer disease , anorexia
and bulimia , depressive disorder , schizophrenia
, etc. Currently, the possibility of BDNF participa
tion in migraine pathogenesis is discussed .
The article was translated by the authors.
One of most studied SNPs in
gene is G/A
substitution in 196 position of exon 8 (rs6265), which
results in substitution in codon 66 of Val into Met ami
noacid in 5' proBDNF domain. However, this substi
tution does not affect the function of BDNF protein
itself but leads to downregulated BDNFdependent
secretion, dramatically altering intracellular traffick
ing and folding of proBDNF. This may be connected
with increased sensitivity to neuropsychiatric disor
ders including depressions, anxiety, etc. [6–9].
Previously, it was shown that allele A may be asso
ciated with memory dysfunction, disruption of hip
pocampus activation, and hippocampus volume.
Decreased secretion of BDNF in cultured neurons
carrying allele A had been revealed, as well as that
allele A affected intracellular distribution of BDNF
and its depolarizationsensitive secretion .
Therefore, polymorphic locus rs6265 is one of best
studied in BDNF gene, and its role in pathogenesis of
several psychiatric disorders was shown in associative
studies. At the same time, association of polymorphic
loci rs2049046 and rs11030107 with functional activity
gene remains insufficiently explored.
The aim of present study is the analysis of occur
rence rate of three SNPs located in
PCR–RFLP method in randomized selection of
Moscow citizens. Ethnicity of participants was not
taken into account.
In the study, DNA extracted from whole blood of
volunteers living in Moscow was examined. Sample
volume was 204 persons (100 males and 104 females
aged from 18 to 57 years old). Blood sampling was held
in Moscow blood transfusion station. Blood samples
were kindly provided by Laboratory of Functional
Genomics (Vavilov Institute of General Genetics,
BrainDerived Neurotrophic Factor Gene (
among Moscow Citizens
Z. G. Kokaeva, T. O. Kochetkova, E. V. Afonchikova, N. S. Kondratyeva, and E. A. Klimov
Department of Genetics, Lomonosov Moscow State University, Moscow, 119991
Received February 5, 2013
—Recent studies showed that brainderived neurotrophic factor (BDNF) can participate in patho
genesis of various CNS disorders, being connected with proliferation, differentiation, and survival of neu
rons. In present study, analysis of occurrence rate was performed for three single nucleotide polymorphisms
(SNPs) located in
gene (rs6267 (A/G) allele A—0.265; rs2049046 (A/T) allele A—0.407; rs11030107
(A/G) allele A—0.872) in randomized selection of Moscow citizens. Linkage disequilibrium of rs6165 and
rs2049046 loci was shown. Differences in allele frequencies in studied selection and populations of other
regions were discovered.