Polymorphism Of Coagulation Factor Research Articles

ETIOPATHOGENESIS OF RECURRENT PREGNANCY LOSS DUE TO GENETIC FORMS OF THROMBOPHILIA

The aim of the study was to develop a concept of the etiopathogenesis of miscarriages due to the genetic form of thrombophilia.
 Materials and methods. In a prospective cohort study, 143 pregnant women were examined, including 109 with pregnancy loss and genetic defects of hemostasis [main (M) group]; the control (K) group consisted of 34 relatively healthy pregnant women with a light history and pregnancy without risk factors for pregnancy loss. Genetic polymorphisms of coagulation factors and fibrinolysis (1691 G→A FVL, 20210 G→A prothrombin, 675 5G/4G PAI-1, 455 G→A fibrinogen β), endothelial dysfunction (677 C→T MTHFR) were studied with the help of allele-specific polymerase chain reaction.
 Results. A comprehensive clinical, laboratory, instrumental and statistical analysis has determined the main risk factors for pregnancy loss. Pathological polymorphisms of hemostasis and endothelial dysfunction genes play an important role in the development of miscarriage, namely the following pathological genotypes: 1691 GA factor V Leiden - increases the risk by 5.3 times (95% CI 1.5-18.5), 20210 GA prothrombin - 26.47 times (1.6-445.7), 675 4G / 4G PAI-1 - 7.5 times (1.7-33.79), -455AA fibrinogen β - 9.7 times (1.3-74.16), 677 CT MTHFR - 2.6 times (1.0-6.2), 677TT MTHFR - 21.7 times (1.3-368.6). It has been found that multigenic forms of thrombophilia predominate in most patients with pregnancy loss - 76.1% (p <0.001, OR = 12.31, 95% CI 4.8-31.55).
 Conclusions. The obtained data allowed us to form a concept of the etiopathogenesis of recurrent pregnancy loss due to genetic thrombophilia and justify the need for a personalized approach in each case of pregnancy loss.

RISK OF PLACENTA-ASSOCIATED COMPLICATIONS AT PREECLAMPSIA IN PREGNANT WOMEN WITH THROMBOPHILIA.

The aim: To study the distribution and influence of coagulation factor gene polymorphisms, endothelial dysfunction, blood pressure regulator on the development of obstetric and perinatal complications in women with preeclampsia (PE). Materials and methods: The prospective cohort study included 46 women with PE and maternal or fetal complications and 87 pregnant women with PE, without complications. Genetic polymorphisms of coagulation factors and fibrinolysis (1691 G→A FVL, 20210 G→A prothrombin, 675 5G/4G PAI-1, 455 G→A fibrinogen β), endothelial dysfunction (192 Q→R PON-1, 677 C→T MTHFR) and blood pressure regulator (235 M→T angiotensinogen II) were studied with the help of allele-specific polymerase chain reaction. Results: Markers of predisposition to the development of obstetric and perinatal complications in pregnant women with PE are the following genotypes: 1691 GA by V Leiden factor gene - increases the risk in 2.9 times (95% CI 1.94-4.33), 20210 GA by prothrombin gene - in 2.36 times (95% CI 1.54-3.6), 20210 AA by prothrombin gene - in 3.12 times (95% CI 2.4-4.0). Pathological polymorphisms in the genes of angiotensinogen II 235 M→T, PAI-1 5G/4G, fibrinogen β 455 G→A, paraoxonase-1 192 Q→R do not significantly affect the development of complications during preeclampsia. Conclusions: The development of PE against the background of the existence of acquired and hereditary types of thrombophilia is associated with a more severe course, early-onset and the development of life-threatening complications for a mother and fetus.

Gene polymorphism of blood coagulation factors and endothelial dysfunction in early and late preeclampsia.

The aim of our study was to find out the influence of gene polymorphisms of coagulation factors, endothelial dysfunction and regulators of blood pressure in early (EPE) and late preeclampsia (LPE). The study of genetic polymorphisms of blood coagulation factors and fibrinolysis (1691 G/A factor V Leiden (FVL), 20210 G/A prothrombin, -675 5G/4G PAI-1, 455 G/A fibrinogen β), endothelial dysfunction (192 Q → R paraoxonase 1, 677 C/T MTHFR, arterial pressure regulator (235 M/T angio­tensinogen II (AGT II)) using an PCR was performed. A prospective cohort study of 39 women with EPE, 93 with LPE and 44 pregnant women with a physiological pregnancy (C group) was conducted. The average gestational age at the time of delivery in EPE group was lower than in LPE and control group (p<0.001). In group with EPE new-borns had low weight-growth characteristics, low grade by the Apgar scale and foetal distress (38.5% vs. 9.7%, p<0.05). Caesarean section in EPE group was performed by 2.25 times more often than in control group and by 2,13 times than in LPE group (p<0,05). It was detected that the number of 1691 GA FVL heterozygote carriers in the group with EPE was significantly higher than in LPE group (p<0.05, OR=3.65, 95% CI 1.5-8.9) and control group (6.04, 1.7-21.6). The number of 20210 GG homozygotes and 20210 GA heterozygotes in prothrombin gene was probably lower in EPE group compared with the LPE and control group (0.03, 0.002-0.49, and 0.18, 0.06-0.53, respectively). It was established increase in frequency of 677 TT MTHFR genotype in EPE compared with control group (17.27; 0.9-317). Also, the carriers of 235T allele AGT II gene have an increased risk of EPE and PPE development (2.25, 1.2-4.2), (1.9, 1.1-3.3) respectively. The allele -455A of fibrinogen β gene increases the chances of developing EPE by 4.4 times (2.0-9.5), and LPE by 3.5 times (1.7-7.1). Risk factors that significantly increase the chances of developing early preeclampsia were identified: allele 1691 A of FV Leiden (5.96, 1.5-8.9), allele 20210 A of prothrombin (39.8, 2,3-679), 677T MTHFR (2.5, 1.18-5.3). In was detected that other researched polymorphisms between groups with PE were not significantly different and did not affect on time of preeclampsia development.

The Cause of the Bleeding and Thrombosis in Patients with Implanted Left Ventricular Assist Devices

Chronic heart failure (CHF) is one of the most severe and adverse diseases of the cardiovascular system, which requires heart transplantation (HT) for patient. Implantation of the left ventricular assist device (LVAD) is the treatment option instead of HT. LVAD can be implanted as a bridge to transplantation and destination therapy (DT). Unfortunately, DT of the LVAD has side effects such as bleeding and thrombosis. These side effects occur because of the non-physiological high shear stress of the LVAD, which causes platelet degradation. However, side effects might occur because of the genetic polymorphisms in coagulation factors, platelet receptors etc. The purpose of the study is to identify the influence of the coagulation factor F5, F7 and FGB polymorphisms in LVAD patients. Venous blood samples were recruited from 100 patients with implanted LVAD at the National Research Center for Cardiac Surgery. Patients were prescribed with the dose of the warfarin according to the clinical protocol. Patients were divided into two groups: 1.Case study - patients with side effects; 2. Control study - patients without side effects. Genomic DNA was extracted by using the PureLink™ Genomic DNA Mini Kit (Invitrogen, UK). Genotyping of polymorphisms F5 (rs6025), F7 (rs6046) and FGB (rs1800790) was done by real-time polymerase chain reaction with TaqMan probes. Genotyping results of Factor Leiden V (F5) showed that most of the patients (99%) has wild type of genotype (C/C) which has no risk to thrombosis. On other hand, genotyping results of F7 and fibrinogen beta (FGB) polymorphisms presented different percentage results from F5. Results of polymorphism F7 showed wild type of genotype G/G in 76% patients, whereas only 3% patients has mutant genotype A/A which has no risk to thrombosis. Mutant genotype A/A of FGB polymorphism was expressed only in 3% of patients, which has high risk to thrombosis. Mutant version of polymorphisms shows that some LVAD patients have high risk to side effects apart from high shear stress. The study has presented that side effects might happen because of the individual genome differences in LVAD patients. Some patients demonstrated high risk of side effects on destination therapy as well as according to genotyping results too.

A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X during Acinetobacter baumannii Infection.

Coagulation and inflammation are interconnected, suggesting that coagulation plays a key role in the inflammatory response to pathogens. A phenome-wide association study (PheWAS) was used to identify clinical phenotypes of patients with a polymorphism in coagulation factor X. Patients with this single nucleotide polymorphism (SNP) were more likely to be hospitalized with hemostatic and infection-related disorders, suggesting that factor X contributes to the immune response to infection. To investigate this, we modeled infections by human pathogens in a mouse model of factor X deficiency. Factor X-deficient mice were protected from systemic Acinetobacter baumannii infection, suggesting that factor X plays a role in the immune response to A. baumannii Factor X deficiency was associated with reduced cytokine and chemokine production and alterations in immune cell population during infection: factor X-deficient mice demonstrated increased abundance of neutrophils, macrophages, and effector T cells. Together, these results suggest that factor X activity is associated with an inefficient immune response and contributes to the pathology of A. baumannii infection.

The effect of coagulation factors polymorphisms on abortion

Recent studies showed coagulation factors play important role in controlling pregnancy duration in addition to controlling homeostasis. Recent studies showed several polymorphisms of coagulation factors genes increase the clot formation and lead to abortion. In this study, we evaluated the polymorphisms of coagulation factors and their effects on the development of the fetus. Relevant literature was identified by a PubMed search (1988-2017) of English language papers using the terms Abortion, pregnancy woman, coagulation factor and polymorphism. Several polymorphisms of coagulation factors disturb the exchange of food and other materials between the fetus and the mother, and impairs the formation of the placenta during embryonic stages. Evaluation of functional polymorphisms in coagulation factors gene during fetal development can be used as a prognostic factor in the prevention of the abortion.

Genetic Polymorphisms of coagulation factors and platelet glycoproteins in patients with chronic myeloproliferative neoplasms

Genetic Polymorphisms of coagulation factors and platelet glycoproteins in patients with chronic myeloproliferative neoplasms

Correlation of Thrombosis and Prothrombotic State with Coagulation Factor V Gene Polymorphism and APCR. HHcy

To investigate the correlation of patients with thrombosis or prothrombotic status with hyperhomocysteinemia (HHcy), activated protein C-resistance(APCR) and gene polymorphism of coagulation factor V. Three hundred healthy voluteers were selected as controls, 223 cases of thrombosis (80 cases of cerebral infarction of CT, the MI of 82 cases of myocardial infarction, venous thrombosis of VTE 61 cases), 270 cases of patients with prothrombotic state (76 cases of pregnancy disease of PIH, 62 cases of chronic obstructive pulmonary disease (COPD), 60 cases of diabetes(DM) and 72 cases of cancer) were enrolled in this study. The plasma APCR and hyperhomocysteinemia were detected by APTT coagulation method and cycling enzyme method respectively, and restriction fragment length polymorphism(RFLP) were was used to detect the gene polymorphism of FV G1691-A, G1091-C and A1090-G in the patient and control groups. APCR positive rate was 62.29% and 7.33%, and the positive hyperhomocysteinemia accounted for 68.42% and 10.00% respectively in the group of the patients with venous thrombosis and the normal control group. 3 cases of heterozygous FV gene mutations were found in the APCR-positive patients with venous thrombosis. HHcy possitive rate of patients with venous thrombosis is signiticantly higher than that in control, the HHcy is one of the important causes resulting in thrombosis, the patients with venous thrombosis have proved to be with APCR, and the possitive APCR may be related with the coagulation factor V gene polymorphism.

Association between the C46T polymorphism of coagulation factor Ⅻ gene and the involvement of factor Ⅻ activity in patients with unexplained recurrent spontaneous abortion

To explore the association between the C46T polymorphism of coagulation factor Ⅻ (FⅫ) gene and the involvement of FⅫ activity (FⅫ:C) in patients with unexplained recurrent spontaneous abortion (URSA), and to elucidate its role in the pathogenesis of URSA. This study included 203 patients with URSA (URSA group) and 171 healthy women with at least one child and no history of infertility or miscarriage (control group) in the southern area of Zhejiang Province. The C46T polymorphism of the FⅫ gene was analyzed with matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS) in all subjects. The values of prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, FⅫ:C and other coagulant parameters were determined. The frequency distribution of the wild-type (CC), heterozygote (CT), homozygote (TT) genotypes and C and T alleles were compared between the patients and controls. A comprehensive analysis of association was conducted between C46T genotypes and the FⅫ:C levels in URSA patients. The CC, CT, TT genotypes of the FⅫ gene were observed in 7 (3.4%, 7/203), 83 (40.9%, 83/203) and 113 (55.7%, 113/203) patients with URSA versus 7 (4.1%, 7/171), 46 (26.9%, 46/171) and 118 (69.0%, 118/171) controls. The frequency of CT in the patients with URSA was significantly higher than that in controls, but the frequency of TT in the patients was lower than that in controls (χ(2)=7.939, OR=1.884, 95%CI: 1.210-2.935, P<0.05). The frequencies of allele C and allele T were observed in 97 (23.9%, 97/406) and 309 (76.1%, 309/406) patients with URSA versus 60 (17.5%, 60/342) and 282 (82.5%, 282/342) controls. The distribution frequency of allele T in URSA group was lower than that in control group (χ(2)=4.510, OR=1.475, 95%CI: 1.029-2.115, P<0.05). The FⅫ: C levels in the patients were (102±13)% in CC genotype, (78±11)% in CT genotype and (59±9)% in TT genotype, respectively. The differences of the FⅫ: C levels between the CC and CT, CT and TT, CC and TT genotypes in the patients were significant (all P<0.05). The low level of FⅫ:C maybe result from the T allele of the FⅫ gene in URSA patients. The CT genotype might be relative to the pathogenesis of URSA in a Chinese Han female population from the southern area of Zhejiang province.

Multigenic forms of thrombophilia in habitual miscarige.

Miscarriage is an actual problem of modern obstetrics. The frequency of miscarriage is 10-25% of all pregnancies, and habitual abortion occurs in 5%. Habitual miscarriage is considered as a typical multifactorial disease, being the result of expression of functionally weakened versions of many genes on the background of adverse external and internal factors. The genetic nature of habitual miscarriage includes groups of genes responsible for hemostatic disorders and endothelial dysfunction. The aim of the study was to determine the frequency and the role of combination of allelic variants of thrombophilia genes and endothelial dysfunction in the development of habitual miscarriage. 109 women with recurrent miscarriage and 34 apparently healthy pregnant women were tested with allele specific polymerase chain reaction and genetic polymorphisms of coagulation factors and fibrinolysis (1691 G → A factor V Leiden, 20210 G → A prothrombin, 5G/4G PAI-1, -455 G → A fibrinogen β) and endothelial dysfunction (192 Q → R PON-1, 677 C → T MTHFR) were identified. The study showed the expediency of examination of women with habitual miscarriage for the presence of an inherited defect in the hemostatic system (gene mutations factor V Leiden, prothrombin 20210G → A, polymorphism of PAI-1 5G / 4G, fibrinogen β -455 G → A) and endothelial dysfunction (MTHFR gene polymorphism 677 C → T). A high frequency of multigene form of thrombophilia (two or more defects) in patients with habitual miscarriage - 80.7% was detected. Pathologic polymorphisms that cause fibrinolysis defects in combination with dysfibrinogenemia were identified the most frequently.

Genotyping analysis for the 46 C/T polymorphism of coagulation factor XII and the involvement of factor XII activity in patients with recurrent pregnancy loss.

BackgroundEstablished causes of recurrent pregnancy loss (RPL) include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations and abnormal embryonic karyotype. A systematic review concluded that coagulation factor XII (FXII) deficiency was associated with RPL. However, it could not be established whether the 46 C/T SNP of FXII or low activity of FXII was a risk factor for RPL, because of the small sample size.Methods and FindingsWe conducted a cross-sectional and cohort study in 279 patients with two or more unexplained consecutive pregnancy losses and 100 fertile women. The association between the lupus anticoagulant (LA) activity and FXII activity was examined. The frequency of the CC, CT and TT genotypes and the FXII activity were also compared between the patients and controls. Subsequent miscarriage rates among the CC, CT, TT genotypes and according to the FXII activity was examined. LA was associated with reduced FXII activity. The CT, but not the TT, genotype was confirmed to be a risk factor for RPL in the cross-sectional study using multivariate logistic regression analysis (OR, 2.8; 95% CI, 1.37–5.85). The plasma FXII activity in the patients was similar to that in the controls. Neither low FXII activity nor the CT genotype predicted the subsequent pregnancy outcome in the cohort study. On the other hand, and intermediate FXII activity level of 85–101% was predictive of subsequent miscarriage.ConclusionsLow FXII activity was not associated with RPL. The FXII gene was found to be one of the significant susceptibility genes for RPL, similar to the FV Leiden mutation. However, the clinical influence of the CT genotype might be relatively small, because the presence/absence of this genotype did not have any predictive value for the subsequent pregnancy outcome. This was the first study indicating the influence of FXII 46C/T on further pregnancy outcomes.

Genotyping analysis for the 46C/T polymorphism of coagulation factor XII and the involvement of factor XII activity in patients with recurrent pregnancy loss

Genotyping analysis for the 46C/T polymorphism of coagulation factor XII and the involvement of factor XII activity in patients with recurrent pregnancy loss

GW25-e0503 The congenital and acquired thrombophilia in Chinese pulmonary thromboembolism patients

The genetic polymorphisms of coagulation factor V Leiden and prothrombin G20210A are common risk factors of inherited thrombophilia in Caucasians, but rare in Aisan. Factor V is an substrate of the activated protein C anticoagulant system. While in Asian population, dysfunction of APC system

Activated Protein C Anticoagulant System Dysfunction and Thrombophilia in Asia

Thrombophilia that is common among Caucasians is caused by genetic polymorphisms of coagulation factor V Leiden (R506Q) and prothrombin G20210A. Unlike that in Caucasians, thrombophilia that is common in the Japanese and Chinese involve dysfunction of the activated protein C (APC) anticoagulant system caused by abnormal protein S and protein C molecules. Approximately 50% of Japanese and Chinese individuals who develop venous thrombosis have reduced activities of protein S. The abnormal sites causing the protein S molecule abnormalities are distributed throughout the protein S gene, PROS1. One of the most common abnormalities is protein S Tokushima (K155E), which accounts for about 30% of the protein S molecule abnormalities in the Japanese. Whether APC dysfunction occurs in other Asian countries is an important aspect of mapping thrombophilia among Asians. International surveys using an accurate assay system are needed to determine this.

Polymorphisms of Genes Encoding Coagulation Factors II, V, VII, and XIII in Relation to Pediatric Ischemic Stroke

The investigation of a possible association between the FII, FV, FVII, and FXIII genes polymorphisms and pediatric ischemic stroke (IS). The study group consisted of 392 individuals, including 81 children with IS, their biological parents (n=162), and 149 control children. The polymorphisms were genotyped using polymerase chain reaction-restriction fragments length polymorphism method. The relation between analyzed polymorphisms and the disease was tested by 2 independent methods: family-based association test-transmission/disequilibrium test (TDT) and classic case-control model. We did not observe any preferential distribution of any analyzed allele from parents to the affected children. For the FVII gene polymorphism, there was a trend toward a higher frequency of the R allele. In a case-control model, the differences between the patients and controls in the frequency of the Q allele, Q allele carriers, and RR homozygotes lay close to the border of statistical significance (P=0.08). There were no significant differences in genotype and allele distribution between patients and controls in case of other polymorphisms. Analyzed polymorphisms of coagulation factors are not significant determinants of pediatric IS in the studied population; however, these findings require a confirmation in a larger group of participants.

Association of C46T genetic polymorphism of coagulation factor XII with deep venous thrombosis: a cohort study on Egyptian patients

Deep vein thrombosis (DVT) is a common multi-factorial disease, with serious short- and long-term complications, and a potential fatal outcome. Many genes are involved in determining the interindividual variation in traits that define the onset and progression of disease, as well as the response to treatment. Several association studies have designed the relationship between factor XII C46T polymorphism and the risk of arterial and venous thrombosis. Some studies reported that FXII gene polymorphism is not associated with venous thrombosis, whereas other studies found an increased risk of venous thrombosis in carriers of a FXII-T variant. We constructed an age–gender–ethnic–matched case–control study including 52 DVT patients and 100 healthy volunteers. C46T polymorphism of the coagulation factor XII was carried out using allelic discrimination assay by real-time polymerase chain reaction for patients and controls, while plasma factor XII activity was detected by one-step clotting assay. FXII C46T genotyping in DVT patients revealed that 34.6% were heterozygous harboring the FXII-CT heterotype and 3.85% were homozygous; FXII-TT homotype, with no statistically significant difference in the distribution of the mutant genotypes between DVT patients and the control group. FXII activity was significantly reduced in DVT patients harboring the mutant genotypes. In the present study, FXII C46T gene polymorphism was not associated with increased risk of deep venous thrombosis.

Association of PAI‐1 gene polymorphism with survival and chemotherapy‐related vascular toxicity in testicular cancer

High Plasminogen-Activator Inhibitor 1 (PAI-1) expression by tumors has been associated with poor prognosis in several cancer types, and high systemic PAI-1 levels with increased thrombosis risk. The authors investigated whether the germline 4G/5G deletion/insertion polymorphism in the PAI-1 promoter (rs1799889), which may influence PAI-1 expression, is associated with survival and chemotherapy-related vascular toxicity in testicular cancer (TC). Data were collected on PAI-1 4G/5G polymorphism, survival, venous thromboembolism (VTE), and coronary heart disease (CHD) for 324 non-seminomatous TC patients treated with platinum-based chemotherapy. Genotypes were compared regarding survival and disease outcome. VTE and CHD incidence were compared with adjustment for cardiovascular risk factors and prothrombotic gene polymorphisms of coagulation factors II/prothrombin (G20210A) and V (G1691A). The 4G/4G variant of PAI-1 4G/5G polymorphism shows a higher prevalence of International Germ Cell Cancer Classification (IGCCC) poor prognosis compared with 4G/5G and 5G/5G (24% vs 8% and 15%; chi-square P = .003). In addition, the 4G/4G variant shows reduced TC-related survival with a hazard ratio of 2.69 (95% CI, 1.26-5.73; P = .010) for TC-related death (adjusted for IGCCC). This is related to an increased risk for refractory disease and early relapses (odds ratio, 3.35; 95% CI, 1.48-7.59; P = .004). PAI-1 4G/5G polymorphism is not associated with VTE and CHD risk. The 4G/4G variant of PAI-1 4G/5G polymorphism may be an unfavorable prognostic as well as predictive factor for response to chemotherapy in TC patients. If confirmed, it may contribute to the identification of patients with increased risk for refractory disease.

Polymorphisms in coagulation factors and the risk of recurrent cardiovascular events in men after a first myocardial infarction.

The aim of this study was to examine whether genetic predisposition to high levels of coagulation factors influences the risk of developing fatal and non-fatal arterial cardiovascular events in men with a first myocardial infarction (MI). We performed a cohort study among 542 MI patients with a mean age of 56 years (range 32-70 years) at the time of the event. All of the men had a first MI between 1990 and 1996 and were followed until 1 September 2004. DNA was analyzed for polymorphisms of fibrinogen, prothrombin (factor II), factor V, factor VII and plasminogen activator inhibitor type 1, all of which are associated with gain of function of the protein. We collected information from hospital files and general practitioners on the occurrence of major arterial events. In total, 254 major arterial cardiovascular events occurred during a median follow-up period of 11 years (range 0.2-15 years). The point estimates of the relative rates (RRs) of these events for the variant genotypes were all between 0.7 and 1.1 except for the prothrombin 20210A mutation: RR 1.8 (95% confidence interval 0.8-4.1). These findings suggest that there is no association between coagulation factor polymorphisms, previously associated with plasma levels, and the risk of recurrent cardiovascular events.

Genetics of thrombophilia: impact on atherogenesis.

The goal of this review is to present an update on basic and epidemiological findings associating variants in prothrombotic genes with atherogenesis and atherothrombotic disease. The relation between atherosclerosis and thrombosis has long been recognized but only recently has it been understood that certain hemostatic factors affect not only thrombus formation, but also have a direct atherogenic role. Atherosclerosis is a complex disorder that results from the interaction of multiple genetic and environmental factors. Numerous polymorphisms and mutations in genes related to the hemostatic system and to vascular redox determinants that modulate nitric oxide bioavailability have been identified in the past decade; their role in atherogenesis and the risk of cardiovascular disease, however, remain uncertain. We will discuss the functional implications and association with disease risk of polymorphisms in coagulation factors (fibrinogen, prothrombin, and factor V); fibrinolytic factors (plasminogen activator inhibitor 1 and lipoprotein(a)); platelet surface receptors; and vascular redox determinants (methylenetetrahydrofolate reductase, endothelial nitric oxide synthase, and the antioxidant enzymes cellular glutathione peroxidase and paraoxonase). Overall, these genetic variants have a modest effect on risk when considered individually but gain potency when acting synergistically with other genetic or environmental risk factors. We conclude that a better characterization of these interactions, in addition to the identification of potential novel genetic determinants, constitute key issues in the future understanding of the pathogenesis of atherothrombosis.

Cerebral ischemia in young adults and genetic polymorphisms of coagulation factors II, V and VII

Cerebral ischemia in young adults and genetic polymorphisms of coagulation factors II,V and VII -