1. Polymorphisms in FVII and eNOS genes
and risk of ischemic stroke
in patients with obesity
Introduction:
Ischemic stroke is a complex pathology, with a variety of
genetic and environmental factors that influence it’s
pathogenesis. Since polymorphisms in the coagulation
factor VII gene (FVII) contribute to variations in plasma
levels of factor VII, and polymorphisms in the endothelial
NO synthase gene (eNOS) influence the functional activity
of the enzyme and affect the susceptibility to
atherogenesis, they may be associated with the risk of
ischemic stroke. On the other hand, one of the known
stroke risk factors is obesity to be investigated for its
individual effect and interaction with genetic factors on
the association with stroke.
Aim of the study:
The aim of the study was to evaluate the association
between the FVII R353Q and eNOS 4a4b polymorphisms
and ischemic stroke with obesity as a risk factor.
Sample collection:
Case-control study including 179 patients aged 39 to 81
years with ischemic stroke and 88 patients aged 59 to 92
without stroke has been performed, as well as population
control (100 individuals from Ukrainian population).
Methods:
► DNA was extracted from blood samples using the
standard proteinase K phenol-chloroform extraction
method.
► The genotypes of FVII R353Q polymorphism were
determined by the PCR followed by RFPL analysis. The
genotypes of eNOS 4a4b were determined by the PCR with
the banding pattern on gel electrophoresis.
► Statistical analysis was performed using Fisher exact
test (differences were considered significant at P<0.05
level) and odds ratio calculation.
Results:
FVII R353Q and eNOS 4a4b genotypes frequencies in
investigated groups are shown on Figure 1.
► No significant difference in allele and genotype
distribution of eNOS and FVII genes was found
between two control groups.
► No significant association was found between
ischemic stroke and the eNOS 4a4b polymorphism
(OR – 1.04; 95% CI, 0.6–1.8; P= 0.45).
► Analysis of the FVII R353Q polymorphism showed
a marginal association with ischemic stroke
(OR – 1.67; 95% CI, 0.94–3; P= 0.046).
► Obesity itself showed a strong association with
ischemic stroke
(OR – 2.35; 95% CI, 1.51–4.8; P= 0.008).
► While analyzing the joint effects of eNOS 4a4b and
FVII R353Q polymorphisms and obesity interactions
between these risk factors were revealed – the FVII
RR carriers with obesity had significant susceptibility
to ischemic stroke
(OR – 4.03; 95% CI, 1.6–9.8; P= 0.003)
as well as the carriers of eNOS 4a allele with obesity
(OR – 2.91; 95% CI, 1.04–10; P= 0.02).
► Moreover, risk of ischemic stroke in both FVII RR
and eNOS 4a allele carriers with obesity was 5.1 times
higher against all other genotypes
(OR – 5.1; 95% CI, 1.1–22; P= 0.006).
Odds Ratios of studied factors are shown on Figure 2.
IF YOU HAVE ANY QUESTIONS OR PROPOSITIONS
DON’T HESITATE TO CONTACT US:
Mail to: IMBG NASU, Department of Human Genomics,
150 Zabolotnogo str., Kyiv-03680, Ukraine
Tel/Fax:+38 044 526 07 69
E-mail: Livshits@imbg.org.ua,
MarinaBurlova@gmail.com
Burlova-Vasylieva M. K.1, Kravchenko S.A.2, Livshits L.A.2
1. Educational and Scientific Centre “Institute of Biology” of Taras Shevchenko National University of Kyiv, Ukraine
2. Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, Department of Human Genomics, Kyiv, Ukraine
Conclusion:
Our findings suggest that RR genotype of
FVII gene and 4a allele of eNOS gene are
associated with ischemic stroke
susceptibility among patients with obesity.
100
Fig. 1. FVII R353Q and eNOS 4a4b
genotypes frequencies in studied groups
0
10
20
30
40
50
60
70
80
90
100
Control Ischemic stroke Control Ischemic stroke
FVII
RR
RQ
QQ
eNOS
-
1,000
2,000
3,000
4,000
5,000
6,000
eNOS-4a FVII-RR obesity obesity +
eNOS-4a
obesity +
FVII-RR
obesity +
FVII-RR +
eNOS-4a
Odds Ratios
* - statistically significant difference
4b4b
4a4b
4a4a
*
*
*
*
*
Fig. 2. Odds Ratios of studied factors