Polymorphisms in FVII and eNOS genesand risk of ischemic stroke

in patients with obesity

Introduction: Ischemic stroke is a complex pathology, with a variety ofgenetic and environmental factors that influence it’spathogenesis. Since polymorphisms in the coagulationfactor VII gene (FVII) contribute to variations in plasmalevels of factor VII, and polymorphisms in the endothelialNO synthase gene (eNOS) influence the functional activityof the enzyme and affect the susceptibility toatherogenesis, they may be associated with the risk ofischemic stroke. On the other hand, one of the knownstroke risk factors is obesity to be investigated for itsindividual effect and interaction with genetic factors onthe association with stroke.

Aim of the study:The aim of the study was to evaluate the associationbetween the FVII R353Q and eNOS 4a4b polymorphismsand ischemic stroke with obesity as a risk factor.

Sample collection:Case-control study including 179 patients aged 39 to 81years with ischemic stroke and 88 patients aged 59 to 92without stroke has been performed, as well as populationcontrol (100 individuals from Ukrainian population).

Methods:► DNA was extracted from blood samples using the

standard proteinase K phenol-chloroform extractionmethod.► The genotypes of FVII R353Q polymorphism weredetermined by the PCR followed by RFPL analysis. Thegenotypes of eNOS 4a4b were determined by the PCR withthe banding pattern on gel electrophoresis.► Statistical analysis was performed using Fisher exacttest (differences were considered significant at P<0.05level) 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 genotypedistribution of eNOS and FVII genes was foundbetween two control groups.► No significant association was found betweenischemic stroke and the eNOS 4a4b polymorphism(OR – 1.04; 95% CI, 0.6–1.8; P= 0.45).► Analysis of the FVII R353Q polymorphism showeda marginal association with ischemic stroke(OR – 1.67; 95% CI, 0.94–3; P= 0.046).► Obesity itself showed a strong association withischemic stroke(OR – 2.35; 95% CI, 1.51–4.8; P= 0.008).► While analyzing the joint effects of eNOS 4a4b andFVII R353Q polymorphisms and obesity interactionsbetween these risk factors were revealed – the FVIIRR carriers with obesity had significant susceptibilityto 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 RRand eNOS 4a allele carriers with obesity was 5.1 timeshigher 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, Ukraine2. 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 ofFVII gene and 4a allele of eNOS gene areassociated with ischemic strokesusceptibility among patients with obesity.

100

Fig. 1. FVII R353Q and eNOS 4a4bgenotypes frequencies in studied groups

0

10

20

30

40

50

60

70

80

90

100

Control Ischemic stroke Control Ischemic stroke

FVII

RRRQQQ

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

4b4b4a4b4a4a

**

**

*

Fig. 2. Odds Ratios of studied factors