Transcript Polymorphisms in the CRP and C1Q genes and - dr

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
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%
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.
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
Subjects and methods

Study population
◦ patients with paranoid schizophrenia n=103
◦ healthy subjects n=105
◦ 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 sequencespecific primers (PCR-SSP)
◦ Statistical analysis: Pearson’s Chi-square test was
performed for analysis of genotyping data.
Results: CRP
Proportion of mutant allele frequencies
0,35
0,3
Control
rs1417938
rs1205
0,25
0,2
0,15
0,1
0,05
0
Schizophrenia
rs1800947
Results : CRP
60
Control
50
Schizophrenia
rs1205
P=0.1
40
30
20
rs1417938
P=0.1
10
0
AA homozygotes
T carriers
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
(P>0.05).
Results: C1QB
Proportion of mutant allele
100
rs291982
Pn=0.01; OR=0,46
0.5346<CI<0.9084
80
60
40
20
0
Control
Schizophrenia
Results: C1QB

The distribution of genotypes for both C1QB SNPs
corresponded to the Hardy-Weinberg equilibrium

The carriers of the C1QB rs291982*T allele
were significantly less frequent in patients
with schizophrenia compared to control subjects
(Pnominal=0.01, Pcorr=0.05)

No association between the C1QB rs631090 SNP
and schizophrenia has been found.
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.
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.
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
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
Thank you