Polymorphisms in the Polymorphisms in the CRP CRP and and C1C1QQ genes and schizophrenia genes and schizophrenia in Armenian population: in Armenian population: A A pilot studypilot 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

HypothesisThe functional variants of the CRP and C1Q

genes might be involved in pathogenesis of schizophrenia.

ObjectiveObjective::To investigate possible association of selected variants in CRP and C1Q genes with susceptibility to schizophrenia.

Selected SNP variants:

CRP: rs1417938 (T/A) – intronrs1800947 (C/G) – intronrs1205 (C/T) – UTR-3´C1QB: rs291982 (G/T) – intronrs631090 (T/C) – intron

Subjects and methodsSubjects 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 sequence-specific primers (PCR-SSP)

◦ Statistical analysis: Pearson’s Chi-square test was performed for analysis of genotyping data.

Proportion of mutant allele frequencies

ResultsResults: : CRPCRP

0

0,05

0,1

0,15

0,2

0,25

0,3

0,35 Control Schizophrenia

rs1417938

rs1800947

rs1205

Results Results : : CRPCRP

0

10

20

30

40

50

60

AA homozygotes T carriers

Control

Schizophrenia

rs1417938P=0.1

rs1205P=0.1

ResultsResults: : CRPCRP

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: Results: C1C1QBQB

Proportion of mutant allele

0

20

40

60

80

100

Pn=0.01; OR=0,460.5346<CI<0.9084

rs291982

Control Schizophrenia

ResultsResults:: C1C1QBQB

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.

ConclusionsConclusions

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.

DiscussionDiscussion

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 plansFuture 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: RoksanaRoksana ZakharyanZakharyanPhD Student & Junior researcherInstitute of Molecular Biology, Yerevan, Armenia

AcknowledgementsAcknowledgementsStudy is supported by International Visegrad Fund

Prof. Anna Boyajyan, DrScYeravan, Armenia

Prof. MUDr. Martin Petrek, CSc &MUDr. Frantisek Mrazek, PhD.Olomouc, Czech Republic

Thank youThank you