‫داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ‬
‫و ﺧﺪﻣﺎت ﺑﻬﺪاﺷﺘﻲ و درﻣﺎﻧﻲ آذرﺑﺎﻳﺠﺎن ﻏﺮﺑﻲ‬
Evaluation of DISC1
DISC1 gene rs3738401
rs3738401 polymorphism in Iranian
patients
i affected
ff d by
b SSchizophrenia
hi h i andd iindividuals
di id l
Presented by:
narmin mokarizadeh
Department of Biochemistry, School of Medicine, Urmia University of
M di l SScience,
Medical
i
U i , Iran
Urmia,
Urmia
I
Introduction
Schizophrenia (SCZ) is a complex psychiatric disorder characterized by:
Hallucinations and delusions
Disorganized speech
cognitive impairment
disturbances in emotions and social functioning
Changes in memory and will
defined by a group of characteristic positive and negative symptoms
Negative
Positive
Deficiency
D fi i off speechh
Absence of emotion
surface reactions
Loss of will
Hallucinations
H ll i ti
Delusions
Bizarre behaviour
Aberrant reactions
Escape from the community
Disorganized speech
Diagnosis is based on observed manners and reported experiences
g
p
speech
Disorganized
Onset from adolescence to age 45 (Men have earlier onset ((20
20--28)
28) than
women (26
(26--32).
32).
affects approximately 0.5–1.0% of the global population
Abnormal brain structure and function
Underactive frontal lobes and overactive parietal lobes are thought to cause
some of schizophrenia’s associated symptoms
genetics, epigenetics and environment are important
contributing
ib i ffactors
One ggene frequently
q y associated with schizophrenia
p
is the
Disrupted in Schizophrenia Gene 1 (DISC
DISC11)
A recent review of all genes associated with risk prediction
p
identified DISC
DISC11 as the topp candidate
for schizophrenia
(Ayalew et al., 2012)
2012)
DISC1 is a moderately conserved gene that highly expressed in the central
DISC1
nervous system, particularly in the hippocampus and the cerebral cortex
codes for a 93.
93.6-kDa protein of 854 amino acids
plays a role in both neural signalling and development
Three common missense mutations in DISC
DISC11
R264
264QQ (rs3738401
(rs3738401))
L607
607FF (rs6675281
(rs6675281))
S704
704CC (rs
(rs821616
821616))
have been variably associated with the risk of schizophrenia
The prevalence of mental illness (particullarly
(particullarly SCZ) in our community is
23..6% (14%
23
14% of the total disease in iran
iran))
In this study we examined the DISC
DISC11 gene rs
rs3738401
3738401
polymorphism And to assess its association with
S hi h i we ddetermined
Schizophrenia,
t i d All
Allelel andd genotype
t
frequencies of rs3738401
rs3738401 polymorphism
in an Iranian population
Material and Methods
¾
¾
¾
71 patients with Schizophrenia After diagnosis based on the approved
clinical protocols and Diagnostic and Statistical Manual (DSM
(DSM--IV),
IV), and
140 healthy controls
Genomic DNA from venous blood samples were isolated using DNA
Extraction Kit PGS (Model: PGS0051
PGS0051)) in accordance with
manufacturer's instructions. DNA were quantified with the NanoDrop
technology
The DISC1
DISC1 gene rsrs3738401
3738401 polymorphism genotyping was performed
base on the amplification
amplification--refractory mutation sequencing (ARMS)
assay
Primer sequence
¾
FC
5’- GTT CCT TTC CCC AGC AGT G -3’
RN
5’-AGA ATG CAT GTC ACG CTC C -3’
RM
5’-AGA ATG CAT GTC ACG CTC T -3’
Statistical analyses were conducted using with the SPSS software
version18
version
18.. Chi
Chi-- square test (χ
(χ2), was used to check the association
between ,two categorical variables or even to detect difference between
several proportions
Results
Results
Patients showed an extensively increased frequency of the
rsrs3738401
3738401 polymorphism allele compared with controls.
there were significantly correlation between DISC1
DISC1 gene
rsrs3738401
3738401 ppolymorphism
y p and Schizophrenia.
p
Therefore,,
DISC11 gene rsrs3738401
DISC
3738401 polymorphism may be a genetic
predisposing
di i ffactor
t ffor SSchizophrenia
hi h i
p
in Iranian ppopulation.
Thankss for
Than
f r yyour
ur aattention
nin