scholarly journals MTHFR Gene Polymorphisms and Cardiovascular Risk Factors, Clinical-Imagistic Features and Outcome in Cerebral Venous Sinus Thrombosis

2020 ◽  
Vol 11 (1) ◽  
pp. 23
Author(s):  
Anca Elena Gogu ◽  
Dragos Catalin Jianu ◽  
Victor Dumitrascu ◽  
Horia Ples ◽  
Alina Zorina Stroe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gene Polymorphisms ◽  
Sinus Thrombosis ◽  
Mthfr Gene ◽  
Prothrombin G20210a ◽  
Factor V ◽  
C Reactive Protein ◽  
Mthfr Polymorphism ◽  
Reactive Protein ◽  
Pai 1

Cerebral venous sinus thrombosis (CVST) as a severe neurological emergency, is represented by variable conditions in its clinic presentation, onset, risk factors, neuroimagistic features and outcome. The genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C was associated with CVST. We aimed to characterize the prevalence of MTHFR gene polymorphisms associated with cardiovascular risk factors in the group of patients with CVST. Also, we studied additional causes associated with CVST including local infections, general infections, obstetric causes (pregnancy, puerperium) and head injury. This is a retrospective study including 114 patients which referred to our hospital between February 2012–February 2020. The protocol included demographic (age, sex), clinical, neuroimagistic features, paraclinic (genetic polymorphism of MTHFR, factor V G1691A—Leiden, prothrombin G20210A, PAI-1 675 4G/5G; Homocysteine level, the lipid profile, blood glucose and Glycohemoglobin HbA1c, high- sensitive C- reactive protein- hsCRP) data, as well as treatment and outcome. The mean age was 37.55 years with a female predominance (65.79%). In the first group of patients with inherited thrombophilia (60 cases; 52.63%) we found genetic mutation includes MTHFR C677T (38.59%) and A1298C (14.03%), factor V G1691A- Leiden (15.78%), prothrombin G20210A (2.63%), PAI-1 675 4G/5G (42.98%), and hyperhomocysteinemia (35.08%). At the second group with other etiology of CVST, except thrombophilia, we included 54 patients (47.36%). The most common sites of thrombosis were the superior sagittal sinus (52.63%). Headache was the most common symptom (91.22%) and seizures were the main clinical presentation (54.38%). The MTHFR polymorphism was significantly correlated with higher total cholesterol (TC) (p = 0.023), low- density lipoprotein cholesterol (LDL) (p = 0.008), homocysteine level (tHcy) (p < 0.001). Inside the first group with MTHFR polymorphism we have found a significant difference between the levels of homocysteine at the patients with MTHFR C677T versus MTHFR A1298C polymorphism (p < 0.001). The high-sensitive C-reactive protein (hsCRP) was increased in both groups of patients, but the level was much higher in the second group (p = 0.046). Mortality rate was of 2.63%. Demographic, clinical and neuroimagistic presentation of CVST in our study was similar with other studies on the matter, with a high frequency of thrombophilia causes. MTHFR gene polymorphisms (C677T and A1298C) are increased in prevalence in CVST. PAI-1 675 4G/5G gene mutation seems to be involved in CVST etiology. Plasma C-reactive protein level and hyperhomocysteinemia should be considered as a prognostic factor in CVST.

Association of increased C-Reactive Protein and hypocomplementemia with risk factors for thrombosis in women who have susceptibility for poor gestational outcome; importance of preconceptional counseling

2021 ◽  
pp. 1-6
Author(s):  
Mehmet Sinan Beksac ◽  
Hanife Guler Donmez
Keyword(s):  
Risk Factors ◽  
Inflammatory Diseases ◽  
Factor V Leiden ◽  
Care Program ◽  
Prothrombin G20210a ◽  
Study Group ◽  
Factor V ◽  
C Reactive Protein ◽  
Mthfr Polymorphisms ◽  
Reactive Protein

This study aimed to investigate the association of increased C-Reactive Protein (CRP) and hypocomplementemia with risk factors for thrombosis such as Factor V Leiden (FVLP) and Prothrombin G20210A polymorphisms (PP), increased Activated Protein C Resistance (APCR) and decreased anti-thrombin III (ATIII) activity in women who have metabolic (MTHFR polymorphisms) and immunological risk factors (autoimmune antibody positivity, autoimmune disorders, and chronic inflammatory diseases). All patients (n= 197) were evaluated in terms of risk factors for thrombosis including FVLP, PP, increased APCR, and decreased ATIII activity as well as CRP and complement (C) 3 and C4 levels within a framework of preconceptional care program. Patients with high CRP levels together with hypocomplementemia were included to the study group (n= 13), while women with normal levels of CRP, C3, and C4 were accepted as controls (n= 184). Decreased ATIII activity was found to be statistically more frequent in the study group compared to controls (p= 0.036). There were no significant differences between the study and control groups in terms of the presence of FVLP, PP and increased APCR (p= 0.386, p= 0.462, p= 0.625, respectively). Decreased ATIII activity should be the concern of preconceptional and antenatal care programs in risky patients with increased CRP levels and hypocomplementemia in order to prevent placental inflammation related gestational complications.

scholarly journals Plasminogen Activator Inhibitor-1 (PAI-1) Gene Polymorphisms Associated with Cardiovascular Risk Factors Involved in Cerebral Venous Sinus Thrombosis

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 266
Author(s):  
Anca Elena Gogu ◽  
Andrei Gheorghe Motoc ◽  
Alina Zorina Stroe ◽  
Any Docu Axelerad ◽  
Daniel Docu Axelerad ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Sinus Thrombosis ◽  
Young Patients ◽  
Plasminogen Activator Inhibitor ◽  
Cerebral Venous Sinus Thrombosis ◽  
C Reactive Protein ◽  
Plasminogen Activator Inhibitor 1 ◽  
Reactive Protein ◽  
Activator Inhibitor ◽  
Pai 1

Cerebral venous sinus thrombosis (CVST), accounting for less than 1% of stroke cases, is characterized by various causes, heterogeneous clinical presentation and different outcome. The plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms has been found to be associated with CVST. The aim of this retrospective study was to determine the potential association of PAI-1 675 4G/5G polymorphisms and homocysteine levels with cardiovascular risk factors in a group of young patients with CVST. Eighty patients with CVST and an equal number of age and sex matched controls were enrolled. The protocol included demographic and clinical baseline characteristics, neuroimagistic aspects, genetic testing (PAI-1 675 4G/5G polymorphisms), biochemical evaluation (homocysteine—tHcy, the lipid profile, blood glucose, glycohemoglobin—HbA1c, high-sensitive C-reactive protein—hsCRP) data, therapy and prognosis. The PAI-1 675 4G/5G gene polymorphisms were significantly correlated with increased homocysteine level (tHcy) (p < 0.05), higher total cholesterol (TC) (p < 0.05), low- density lipoprotein cholesterol (LDLc) (p = 0.05) and high- sensitive C- reactive protein (hsCRP) (p < 0.05) in patients with CVST when compared with controls. From the PAI-1 gene polymorphisms, the PAI-1 675 4G/5G genotype presented statistically significant values regarding the comparisons of the blood lipids values between the CVST group and control group. The homocysteine (tHcy) was increased in both groups, patients versus controls, in cases with the homozygous variant 4G/4G but the level was much higher in the group with CVST (50.56 µmol/L vs. 20.22 µmol/L; p = 0.03). The most common clinical presentation was headache (91.25%), followed by seizures (43.75%) and focal motor deficits (37.5%). The superior sagittal sinus (SSS) was the most commonly involved dural sinus (56.25%), followed by the lateral sinus (LS) (28.75%). Intima—media thickness (IMT) values were higher in the patients’ group with CVST (0.95 mm vs. 0.88 mm; p < 0.05). The fatal outcome occurred 2.5% of the time. PAI-1 675 4G/5G gene polymorphisms and higher homocysteine concentrations were found to be significantly associated with CVST in young patients.

Basal high-sensitivity-C-reactive protein levels in patients with spontaneous venous thromboembolism

2005 ◽  
Vol 93 (03) ◽  
pp. 488-493 ◽  
Author(s):  
Rainer Vormittag ◽  
Thomas Vukovich ◽  
Verena Schönauer ◽  
Stephan Lehr ◽  
Erich Minar ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Statistical Significance ◽  
Factor V Leiden ◽  
High Sensitivity ◽  
Prothrombin G20210a ◽  
Factor V ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hs Crp

SummaryThe role of C-reactive protein (CRP) in venous thromboembolism (VTE) is still under discussion because of controversial results in the literature. Conflicting data may have partly been due to bias by exogenous factors altering CRP levels. We investigated CRP concentrations in patients with spontaneous VTE applying a study design that allowed the measurement of basal high sensitivity (hs)-CRP levels. Patients with a history of deep vein thrombosis (DVT, n=117) and pulmonary embolism (PE, n=97) were compared to healthy individuals (n=104). Hs-CRP levels (mg/dl) were significantly higher in patients (n=214, median/interquartile range: 0.171/0.082–0.366) than in controls (0.099/0.053–0.245, p=0.001). The unadjusted odds ratio (OR) for VTE per 1 mg/dl increase of CRP was 2.8 [95% confidence interval (CI): 1.1–6.8, p=0.03]. This association remained significant after adjustment for factor V Leiden, prothrombin G20210A and factor VIII activity above 230% (OR = 2.9, 95% CI [1.1–7.5]), but became remarkably attenuated and lost its statistical significance after adjustment for BMI alone (OR = 1.7 [0.7–4.0]). CRP was also not independently associated with VTE in subgroups of patients (those with DVT without symptomatic PE, those with PE and patients without established risk factor) in multiple regression analysis. In summary, we observed significantly higher basal hs-CRP levels in patients with spontaneous VTE compared to healthy controls. This association was independent of hereditary and laboratory risk factors for VTE, but lost its significance after adjustment for BMI. Increased basal CRP levels do not appear to represent an independent risk factor for VTE.

scholarly journals Evaluation of pai-1 polymorphisms in central and peripheral thromboembolies

2021 ◽  
Vol 38 (2) ◽  
pp. 167-171
Author(s):  
Özge Arıcı DÜZ ◽  
Oktay OLMUŞÇELİK ◽  
Ali İhsan GEMİCİ ◽  
Özlem SAATÇİ SANCAKTEPE
Keyword(s):  
Risk Factors ◽  
Methylenetetrahydrofolate Reductase ◽  
Vascular System ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Genetic Mutations ◽  
Factor V ◽  
Significant Difference ◽  
Medium Risk ◽  
Pai 1

Thromboembolism is a clinical finding that occurs due to thrombus; formed in the vascular system and has various etiological factors. It can be classified as central and peripheral thromboembolism. Our objective in this study is to explore genetic risk factors in central and peripheral thromboembolism and reveal the differences. 342 thromboembolism patients were retrospectively included to the study between January 2016 and December 2019. Demographic characteristics, risk factors for thromboembolism and genetic mutations in central and peripheral thromboembolism groups were overviewed. The genetic mutations evaluated in patients were Factor V Leiden G1691A, Factor V HR1299R, Factor II (Prothrombin) G20210A, MTHFR (Methylenetetrahydrofolate reductase) C677T, MTHFR A1298C, PAI 4G/5G. Within the scope of the study, genetic analyzes of 106 patients were reached and included in the study. Seventy-two central thromboembolism (69.8%), 34 (31.2%) peripheral thromboembolisms were detected. Sixty-three of the central thromboembolisms were from arterial and nine were from venous origin. There was no significant difference between age, gender and risk factors of central thromboembolism and peripheral thromboembolism patients (p˃0.05), but smoking was more common in central thromboembolism patients (p: 0.041). 4G/5G polymorphism was observed more frequently in patients with central thromboembolism (p: 0.039). Thromboembolism is a multifactorial disease, PAI-1 4G/5G polymorphism is a medium risk factor for thromboembolism. We conclude that PAI-1 4G/5G polymorphism is more frequent in central thromboembolism than peripheral thromboembolism and its evaluation can give more information about the thromboembolic risk analyze.

Prothrombotic Genetic Risk Factors and the Occurrence of Gestational Hypertension with or without Proteinuria

1999 ◽  
Vol 81 (03) ◽  
pp. 349-352 ◽  
Author(s):  
Maurizio Margaglione ◽  
Donatella Colaizzo ◽  
Giuseppe Cappucci ◽  
Natale Sciannamé ◽  
Sergio Montanaro ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gestational Hypertension ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Carrier Status ◽  
Factor V ◽  
Mthfr Polymorphism ◽  
Confounding Variables ◽  
Fv Leiden ◽  
The Impact

SummaryGestational hypertension with or without proteinuria is a multi-factorial disease in which the presence of a hypercoagulable state has been suggested. The prothrombin G20210A, the Factor V (FV) Leiden mutations, and the C677T 5-10 methylenetethrahydrofolate reductase (MTHFR) polymorphism were investigated in 140 women with gestational hypertension and in 216 normotensive women from Southern Italy. Nine controls (4.1%) and 16 cases (11.4%; OR: 2.96, 95% CI: 1.27-6.91) carried the prothrombin A20210 allele. FV Leiden mutation was observed in 4 controls (1.8%) and 11 cases (7.9%; OR: 4.53, 95% CI: 1.41-14.53). The TT MTHFR genotype was found in 36 controls (16.6%) and 34 cases (24.4%; OR: 1.61, 95%CI: 0.96-2.74). The impact of potential confounding variables was evaluated using a logistic regression analysis. Nulliparity, Factor V Leiden and prothrombin A20210 carrier status resulted to be independent risk factors of having gestational hypertension with or without proteinuria. Imbalance of haemostasis, through prothrombotic genetic factors, may predispose to the occurrence of gestational hypertension.

Thrombophilic Risk Factors in Patients with Central Retinal Vein Occlusion

2001 ◽  
Vol 86 (09) ◽  
pp. 722-726 ◽  
Author(s):  
Rossella Marcucci ◽  
Laura Bertini ◽  
Betti Giusti ◽  
Tamara Brunelli ◽  
Sandra Fedi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Retinal Vein Occlusion ◽  
Central Retinal Vein Occlusion ◽  
Methylenetetrahydrofolate Reductase ◽  
Factor V Leiden ◽  
Factor V ◽  
Mthfr Polymorphism ◽  
Vein Occlusion ◽  
Pai 1 ◽  
Central Retinal Vein

SummaryFew and contrasting data are available on the prevalence of hemostatic risk factors in patients with central retinal vein occlusion (CRVO). Aim of this study was to investigate the metabolic and inherited risk factors for venous thrombosis in 100 CRVO patients (age: 59 yrs; range 18-77) and in 100 controls (age: 56 yrs; range 18-84). In patients homocysteine (Hcy) levels were significantly higher than in controls and were affected by the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism (p <0.001). The prevalences of activated protein C resistance (APCR), factor V Leiden positivity, elevated PAI-1 and Lp(a) levels were significantly higher in patients with respect to controls. At multivariate analysis, only hyperhomocysteinemia (OR 11, 95% CI 3.6-36.2; p <0.0001) and elevated PAI-1 levels (OR 8.9, 95% CI 3.5-41.3; p <0.01), in addition to hypertension (OR 40.5, 95% CI 8.6-188.8; p <0.00001) and hypercholesterolemia (OR 3.1, 95% CI 1.6-20.5; p <0.05), were independent risk factors for CRVO. These data demonstrate a potential role of hemostatic risk factors in the pathophysiology of CRVO.

Interaction Between Hyperhomocysteinemia, Mutated Methylenetetrahydrofolatereductase (MTHFR) and Inherited Thrombophilic Factors in Recurrent Venous Thrombosis

2002 ◽  
Vol 88 (11) ◽  
pp. 723-728 ◽  
Author(s):  
Miranda Keijzer ◽  
Henk Blom ◽  
Gerard Bos ◽  
Huub Willems ◽  
Wim Gerrits ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Odds Ratio ◽  
Factor V Leiden ◽  
Mthfr Gene ◽  
Prothrombin G20210a ◽  
Control Group ◽  
Factor V ◽  
Homocysteine Concentration ◽  
Recurrent Venous Thrombosis

SummaryVenous thrombosis is a multicausal disease involving acquired and genetic factors. In this study we investigated a possible interaction between hyperhomocysteinemia (fasting or postload) and factor V Leiden or prothrombin G20210A on the risk of recurrent venous thrombosis. We also looked at the risk due to mutations in the MTHFR-gene (C677T and A1298C).We performed a case-control study in 171 patients with a history of recurrent venous thrombosis and 461 control subjects from the general population. Hyperhomocysteinemia (fasting or 6 h after an oral methionine load) was defined as a homocysteine concentration above the 90th percentile of the distributions in the control group.The odds ratio (adjusted for age and sex) for recurrent venous thrombosis was 1.8 (95%CI: 1.1 to 3.0) for fasting hyperhomocysteinemia, 5.1 (95%CI: 3.0 to 8.6) for factor V Leiden and 1.8 (95%CI: 0.7 to 4.2) for prothrombin G20210A. We found 14 patients and 3 controls with both hyperhomocysteinemia and factor V Leiden, which yielded an odds ratio of 11.6 (95%CI: 3.2 to 42.5). We found no interaction between hyperhomocysteinemia and prothrombin G20210A. The relative risk for MTHFR 677CT was 1.6 (95%CI: 1.1 to 2.4) and for MTHFR 677TT was 1.4 (95%CI: 0.7 to 2.8). The combined risk for MTHFR 677TT and factor V Leiden was 18.7 (95%CI: 3.3 to 108).We conclude that hyperhomocysteinemia and factor V Leiden are risk factors for recurrent venous thrombosis. The risk of thrombosis appeared high for individuals who had both risk factors.

Clotting Factor Gene Polymorphisms and Colorectal Cancer Risk

2011 ◽  
Vol 29 (13) ◽  
pp. 1722-1727 ◽  
Author(s):  
Carla Y. Vossen ◽  
Michael Hoffmeister ◽  
Jenny C. Chang-Claude ◽  
Frits R. Rosendaal ◽  
Hermann Brenner
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Gene Polymorphisms ◽  
Factor V Leiden ◽  
Colorectal Cancer Risk ◽  
Clotting Factor ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor Gene ◽  
Pai 1

PurposeIncreased coagulation has been associated with cancer onset and progression. Mainly small studies have addressed the association between clotting factor gene polymorphisms and the onset of colorectal cancer. We examined the association between six well-known clotting factor gene polymorphisms and colorectal cancer risk in a large case-control study.Patients and MethodsFactor V Leiden (rs6025), prothrombin G20210A (rs1799963), PAI-1 4G/5G (rs1799889), MTHFR 677C>T (rs1801133), fibrinogen gamma 10034C>T (rs2066865), and factor XIII Val34Leu (rs5985) were genotyped in 1,801 patients with colorectal cancer and 1,853 healthy controls from a large German population-based study. The risk of colorectal cancer associated with gene variants was determined by calculating odds ratios (ORs) and their 95% CIs using logistic regression.ResultsHomozygous carriers of the prothrombotic factor V Leiden polymorphism showed a 5.8-fold increased risk (95% CI, 1.69 to 19.72) for colorectal cancer compared with noncarriers. A 30% reduced risk was found for heterozygous carriers of factor V Leiden (OR = 0.68; 95% CI, 0.52 to 0.90) and prothrombin G20210A (OR = 0.69; 95% CI, 0.49 to 0.96), implying an advantage for slightly increased thrombin generation. Carriers of the antithrombotic factor XIII Val34Leu polymorphism showed a 15% reduced risk of developing colorectal cancer (OR = 0.85; 95% CI, 0.74 to 0.97) compared with noncarriers. Our results did not support an effect of PAI-1 4G/5G, MTHFR 677C>T, and fibrinogen gamma 10034C>T on colorectal cancer risk.ConclusionOur results support a role of clotting factor polymorphisms and thereby the coagulation system in the risk of colorectal cancer.

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