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

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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

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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

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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.

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• 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

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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.

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Results CRP
Proportion of mutant allele frequencies
rs1417938
rs1205
rs1800947
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Results CRP
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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).

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Results C1QB
Proportion of mutant allele
rs291982
Pn0.01 OR0,46 0.5346ltCIlt0.9084
Control
Schizophrenia
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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.

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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.

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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.

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• 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

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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
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Thank you