Title:Schizophrenia-associated Risk and Protective Variants of c-Fos Encoding Gene
Volume: 9
Issue: 1
Author(s): Anna Boyajyan, Roksana Zakharyan, Sofi Atshemyan, Andranik Chavushyan and Gohar Mkrtchyan
Affiliation:
Keywords:
c-Fos protein, FOS gene, genetic polymorphisms, plasma levels, schizophrenia, synaptic plasticity.
Abstract: Defects in synaptic plasticity play a key role in pathophysiology of schizophrenia. Pathomechanisms
responsible for synaptic plasticity alterations in schizophrenia are very complicated and not
well defined. Transcription factor c-Fos plays an important role in regulation of synaptic plasticity. In
the present study we evaluated the association of rs7101 and rs1063169 single nucleotide polymorphisms
(SNPs) of c-Fos encoding gene (FOS) with schizophrenia. A total of 604 DNA samples of
schizophrenia-affected and healthy subjects of Armenian ancestry were genotyped using polymerase
chain reaction with sequence-specific primers. Also, comparative determination of the blood levels of c-Fos protein in
schizophrenia patients and controls was performed using the enzyme-linked immunosorbent assay. Potential interaction
between protein level and genotypes as well as relationships between genotypes/protein level and clinical-demographic
characteristics of schizophrenia patients were assessed. The results obtained demonstrated that mutant allele of FOS
rs1063169 SNP is negatively associated with schizophrenia and may be nominated as a protective factor for this disorder.
On the other hand, according to our results, the FOS rs7101T mutant allele is positively associated with schizophrenia
and, therefore, may be considered as a risk factor for this disorder. In addition, decreased c-Fos plasma levels in schizophrenia
patients compared to controls were found. In conclusion, the results of this study suggest that FOS is among the
candidate genes of schizophrenia and that changes in the expression of c-Fos protein may contribute to molecular pathomechanisms
of schizophrenia-related alterations in synaptic plasticity.
