Polymorphisms in the CRP and C1Q genes and schizophrenia in Armenian population: A pilot study - PowerPoint PPT Presentation

About This Presentation
Title:

Polymorphisms in the CRP and C1Q genes and schizophrenia in Armenian population: A pilot study

Description:

Polymorphisms in the CRP and C1Q genes and schizophrenia in Armenian population: A pilot study Zakharyan R1,2, Khoyetsyan A1, Chavushyan A1, Arakelyan A1, Boyajyan A1 ... – PowerPoint PPT presentation

Number of Views:110
Avg rating:3.0/5.0
Slides: 16
Provided by: Arse2
Category:

less

Transcript and Presenter's Notes

Title: Polymorphisms in the CRP and C1Q genes and schizophrenia in Armenian population: A pilot study


1
Polymorphisms in the CRP and C1Q genes and
schizophrenia in Armenian population A pilot
study
  • Zakharyan R1,2, Khoyetsyan A1, Chavushyan A1,
  • Arakelyan A1, Boyajyan A1, Stahelova A2, Mrazek
    F2,
  • Petrek M2,3
  • 1Laboratory of Macromolecular Complexes,
    Institute of Molecular Biology, Yerevan, NAS
    Armenia
  • 2Laboratory of Immunogenomics and Proteomics,
    Dept. of Immunology, Medical Faculty, Palacky
    University, Olomouc
  • 3 Div. of Clinical Biochemistry and
    Immunogenetics, Faculty Hospital, Olomouc

2
Schizophrenia
  • Schizophrenia is a complex mental disease with
    genetic component characterized by behavioral,
    cognitive and social abnormalities
  • According to data provided by the World Health
    Organization (WHO, 2008) this disease affects
    about 7 per thousand of the adult population,
    mostly in the age group 15-35 years (first
    episodes)
  • Disease heritability is about 80, siblings
    recurrence risk is 10

3
CRP ? C1Q in schizophrenia
  • CRP is an acute and chronic phase inflammation
    marker.
  • C1Q is the first and key component of classical
    activation pathway of complement and consists of
    3 subunits C1QA, C1QB, C1QC.
  • The CRP (Hakobyan et al, 2005 Dickerson et al.
    2007) and C1Q (Boyajyan et al, 2008) are
    upregulated in schizophrenia, and likely
    contribute to disease progression
  • Hypothesis
  • The functional variants of the CRP and C1Q genes
    might be involved in pathogenesis of
    schizophrenia.

4
  • Objective
  • To investigate possible association of selected
    variants in CRP and C1Q genes with susceptibility
    to schizophrenia.
  • Selected SNP variants
  • CRP
  • rs1417938 (T/A) intron
  • rs1800947 (C/G) intron
  • rs1205 (C/T) UTR-3
  • C1QB
  • rs291982 (G/T) intron
  • rs631090 (T/C) intron

5
Subjects and methods
  • Study population
  • patients with paranoid schizophrenia n103
  • healthy subjects n105
  • all subjects unrelated Armenians
  • Methods
  • DNA extraction Standard phenol-chloroform method
    using 3-5ml venous blood from subjects of both
    groups
  • Genotyping Polymerase chain reaction with
    sequence-specific primers (PCR-SSP)
  • Statistical analysis Pearsons Chi-square test
    was performed for analysis of genotyping data.

6
Results CRP
Proportion of mutant allele frequencies
rs1417938
rs1205
rs1800947
7
Results CRP
8
Results CRP
  • The distribution of genotypes for all 3 CRP SNPs
    corresponded to the Hardy-Weinberg equilibrium
  • No association between the selected three SNPs in
    the CRP gene and schizophrenia has been found
    (Pgt0.05).

9
Results C1QB
Proportion of mutant allele
rs291982
Pn0.01 OR0,46 0.5346ltCIlt0.9084
Control
Schizophrenia
10
Results C1QB
  • The distribution of genotypes for both C1QB SNPs
    corresponded to the Hardy-Weinberg equilibrium
  • The carriers of the C1QB rs291982T allele were
    significantly less frequent in patients with
    schizophrenia compared to control subjects
    (Pnominal0.01, Pcorr0.05)
  • No association between the C1QB rs631090 SNP and
    schizophrenia has been found.

11
Conclusions
  • Polymorphism rs291982 of the C1QB gene is
    associated with schizophrenia in this pilot
    study.
  • C1QB gene variants or a locus located nearby may
    therefore be involved in susceptibility to
    schizophrenia.
  • No association between the C1QB rs631090 SNP and
    schizophrenia has been found.
  • No association between the selected variants of
    the CRP gene and schizophrenia was observed.

12
Discussion
  • To our knowledge, this is the first study
    investigating a relationship of C1Q gene with
    schizophrenia.
  • According to the recommendation for the genetic
    association studies our results should be
    replicated in independent cohorts.
  • The exact role of C1Q molecules and their gene
    variants in schizophrenia remains to be
    clarified.

13
  • Future plans
  • To enlarge study group for gaining more
    statistical power and for subanalysis according
    to the particular disease phenotypes
  • To evaluate several other CRP polymorphisms to
    achieve more coverage of the gene
  • To investigate additional two SNPs within C1Q
    genes (rs913243 and rs172378) using PCR
    techniques
  • To perform haplotype mapping for C1Q genes

14
Presenting author Roksana Zakharyan
  • PhD Student Junior researcher
  • Institute of Molecular Biology, Yerevan, Armenia

Acknowledgements
Study is supported by International Visegrad
Fund Prof. Anna Boyajyan, DrSc Yeravan,
Armenia Prof. MUDr. Martin Petrek, CSc MUDr.
Frantisek Mrazek, PhD. Olomouc, Czech Republic
15
Thank you
Write a Comment
User Comments (0)
About PowerShow.com