The analysis of alleles and genotypes frequencies of 14 SNP in genes of rennin-angiotensin system (REN, AGT, AGTR1, AGTR2, BKR2, ADRB2) and hemostasis system (FGB, F2, F5, F7, ITGB3, SERPINE1, MTHFR), as well as ACE insertion-deletion polymorphism in patients with stroke comparing to healthy controls matched by age, sex and ethnicity has been carried out. The genotyping procedure included the amplification of selected gene sequences following by hybridization of fluorescently labeled fragments with SNP-specific DNA probes. The analysis of allele frequencies of each gene separately revealed no statistically significant differences between groups of patients with stroke and healthy donors. Also the complex study has been performed to estimate the contribution of rennin-angiotensin system and hemostasis system genes to the genetic susceptibility to ischemic stroke among Russians from Central Russia using method MDR (Multifactor Dimensionality Reduction). The combination with increased risk for development of ischemic stroke was presented by complex genotype FGB G/- x ACE I/- x MTHFR C/- x SERPINE1 5G/5G (p = 0.03, OR = 2.4, 95% CI 1.1-5.3), which frequency was statistically significant higher in patients with stroke compared to healthy control.
OBJECTIVE: Several hemostatic variables are identified as cardiovascular risk markers. In young and middle-aged individuals, plasma concentrations of these variables are partly determined by genetic factors. The genetic contribution to cardiovascular disease (CVD) decreases with increasing age, and it is therefore important to determine the heritability of hemostasis also in the elderly. METHODS: The heritability of plasma levels of factor VII, fibrinogen, tissue factor, tissue factor pathway inhibitor, von Willebrand factor, thrombin activatable fibrinolysis inhibitor (TAFI), and D-dimer was determined in 130 monozygotic and 155 dizygotic same-sex twin pairs, aged 73-94 years, who participated in the Longitudinal Study of Aging of Danish Twins. Furthermore, we determined the influence of promoter polymorphisms in corresponding genes on the plasma level variation. RESULTS: Genetic factors accounted for 33% (D-dimer) to 71% (TAFI) of the variation in plasma levels. Polymorphisms were associated with concentrations of FVII and TAFI in sib-pair based analyses, but in linkage analyses the polymorphisms did not explain a significant part of the genetic variation for any of the variables. CONCLUSIONS: Concentrations of hemostatic variables have a substantial genetic variation in the elderly, but in this study the promoter polymorphisms only explained a minimal part of this variation.
To estimate incidence of carriage of genetic polymorphisms coding hemostasis protein synthesis in patients with venous thromboembolic complications (VTEC) and healthy subjects in Moscow population; to detect VTEC genetic prognostic factors among the polymorphisms.
A total of 111 patients with the history of deep vein thrombosis and/or pulmonary artery thromboembolism were examined. The control groups consisted of 197 healthy volunteers. Eleven polymorphisms in 7 genes coding hemostasis protein synthesis were investigated: V Leiden G1691A factor, G20210A prothrombin, C677T methylentetrahydrofolatreductase, A1298C methylentetrahydrofolatreductase, type 1 plasminogen activator inhibitor, 4G/5G promoter region, XIII V34L coagulation factor, IIIa L33P thrombocytic glycoprotein, C282Y hemochromatosis, G854A beta-fibrinogen, G455A beta-fibrinogen, C249T beta-fibrinogen.
Polymorphisms of the genes coding hemostasis protein synthesis were detected in all the patients and controls. The carriage occurred with the same frequency, respectively. By one-factor analysis, VTEC was associated with carriage of three heterozygous genotypes: V Leiden factor (p
Do extremely old persons have a genetically favourable profile which has protected them from cardiovascular death? We have tried to answer this question by measuring DNA polymorphisms of selected cardiovascular risk indicators [factor VII, FVII (R/Q353, intron 7 (37bp)n, and -323ins10), beta fibrinogen (-455G/A), plasminogen activator inhibitor type 1, PAI-1 (-675(4G/5G)), tissue plasminogen activator, t-PA (intron 8 ins311), platelet receptor glycoprotein IIb/IIIa, GPIIb/IIIa (L/P33), prothrombin (20210G/A), methylene tetrahydrofolate reductase, MTHFR (A/V114), angiotensin converting enzyme, ACE (intron 16 ins287), and angiotensinogen (M/T235)]. Blood was collected from 187 unselected Danish centenarians, and 201 healthy Danish blood donors, aged 20-64 years (mean age 42 years). Genomic DNA was amplified using PCR and the genotype was determined by RFLP methods or allele-specific amplification followed by agarose gel electrophoresis. The frequencies of the high-risk alleles in centenarians were: for FVII R/Q353 0.91; for FVII intron 7 (37bp)n 0.67; for FVII-323 ins10 0.90; for fibrinogen 0.16; for PAI-1 0.52; for t-PA 0.59; for GPIIb/IIIa 0.16; for prothrombin 0.008; for MTHFR 0.33; for ACE 0.52; and for angiotensinogen 0.36. Comparable frequencies were observed in the blood donors. Subgroup analysis of men and women separately gave similar results. The genotype frequencies in the centenarians and the blood donors were similar for all polymorphisms, and this study suggests that common variations in genes associated with cardiovascular risk do not contribute significantly to longevity.
A comparative estimation was conducted to assess the prevalence of genotypes and alleles of the (353)R>Q polymorphism of the coagulation factor FVII gene between a group of the Russian adolescents with essential arterial hypertension and a group of Russian adolescents without such health problems. The RR genotype was diagnosed in 55 adolescents (75.34%) of the control group and in 99 adolescents (84.61%) of the adolescents suffering from essential arterial hypertension (?2 = 1.949, p = 0.163). The frequency of the R-allel was 85% and 91.9%, respectively (?2 = 3.110, p = 0.078). The role of the FVII gene in the determination of the F7 plasma activity was defined in adolescents with essential arterial hypertension and holders of different alleles. Holders of the R allele had significantly higher activity of coagulation factor F7 (97.66 ± 15.48 against 83.37 ± 15.16, p = 0.002) and factor F2 (107.45 ± 6.03 against 103.75 ± 6.81, p = 0.023) than holders of the Q allele. This relationship was not found in adolescents of the control group.