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Poster FEBS 2011_P15.3

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Poster FEBS 2011_P15.3

  1. 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:, 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