Factor V Leiden and Thermolabile Methylenetetrahydrofolate Reductase in Extreme Old Age

1997 ◽  
Vol 78 (05) ◽  
pp. 1357-1359 ◽  
Author(s):  
D C Rees ◽  
Y T Liu ◽  
M J Cox ◽  
P Elliott ◽  
J S Wainscoat
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Factor V Leiden ◽  
Premature Death ◽  
Mthfr Gene ◽  
Factor V ◽  
C677t Mthfr ◽  
C677t Mutation ◽  
Hardy Weinberg Equilibrium ◽  
Mthfr Mutation ◽  
The Uk

SummaryBoth factor V Leiden and the C677T methylenetetrahydrofolate reductase (MTHFR) gene mutation are associated with premature vascular disease, and yet are found at surprisingly high allele frequencies in European populations, 2.7% and 35% respectively. We have investigated the prevalence of these mutations in 87 UK residents over the age of ninety, to look for any evidence of their association with premature death.Five factor V Leiden heterozygotes were found, giving an allele frequency of 2.9%, similar to that in the general UK population. The frequency of the thermolabile C677T MTHFR mutation was 36% with 11% homozygotes, again similar to that in the UK population; these genotypes are in Hardy-Weinberg equilibrium, suggesting that there is not strong selection against the homozygous state. One person was both heterozygous for factor V Leiden and homozygous for the C677T mutation. This study suggests that neither factor V Leiden nor thermolabile MTHFR are risk factors for premature death.

Factor V Leiden, Prothrombin Gene G20210A Variant, and Methylenetetrahydrofolate Reductase C677T Genotype in Young Adults With Ischemic Stroke

2001 ◽  
Vol 7 (4) ◽  
pp. 346-350 ◽  
Author(s):  
Stanislaw Lopaciuk ◽  
Ksenia Bykowska ◽  
Hubert Kwiecinski ◽  
Anatol Mickielewicz ◽  
Anna Czlcankawska ◽  
...  
Keyword(s):  
Young Adults ◽  
Ischemic Stroke ◽  
Methylenetetrahydrofolate Reductase ◽  
Factor V Leiden ◽  
Mthfr Gene ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Control Subjects ◽  
Stroke In Young Adults ◽  
C677t Mutation

Ischemic stroke in young adults is a well-known disease, but despite extensive clinical and laboratory investigations, its etiology remains unclear in approximately half of the cases. We examined the prevalence of factor V Leiden, the prothrombin G20210A genotype, and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in 100 patients (51 males and 49 females) who survived an ischemic stroke without a cardiac embolic source at an age ≤45 years, and in 238 healthy control subjects from the same geographic area. The patients were selected for study only if the diagnosis of stroke was documented by computed tomography scan or nuclear magnetic resonance (NMR) of the brain, or both. Heterozygosity for the FV Leiden mutation was found in 3 patients (3.0%) and in 10 control subjects (4.2%). Two patients (2.0%) and five control subjects (2.1%) were heterozygous for the prothrombin G20210A mutation. The frequencies of the MTHFR 677TT, CT, and CC genotypes in the patient group were 12%, 37%, and 51%, respectively, and were not significantly different from those in control subjects (11%, 40%, and 49%, respectively). In conclusion, our results indicate that FV Leiden mutation, prothrombin G20210A genotype, and homozygosity for the C677T mutation in the MTHFR gene are not associated with an increased risk for ischemic stroke in young adults.

scholarly journals Association of anticardiolipin antibody and C677T in methylenetetrahydrofolate reductase mutation in women with recurrent spontaneous abortions: a new path to thrombophilia?

2005 ◽  
Vol 123 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Egle Couto ◽  
Ricardo Barini ◽  
Renata Zaccaria ◽  
Joyce Maria Annicchino-Bizzacchi ◽  
Renato Passini Junior ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Methylenetetrahydrofolate Reductase ◽  
Factor V Leiden ◽  
Anticardiolipin Antibody ◽  
Mthfr Gene ◽  
Recurrent Spontaneous Abortion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inherited Thrombophilia ◽  
C677t Mutation ◽  
Fertile Women

CONTEXT: Recurrent spontaneous abortion (RSA) has been associated with venous thrombosis in the mother. Acquired and inherited thrombophilia factors are possible causes. OBJECTIVE: To evaluate the association between thrombogenic factors and recurrent spontaneous abortion. TYPE OF STUDY: Case-control study. SETTING: Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas. METHODS: 40 ml of blood was collected from 88 women attending an RSA clinic and 88 fertile women attending a family planning clinic, to evaluate the presence of acquired and inherited thrombophilia factors. Anticardiolipin antibodies (ACA), lupus anticoagulant and deficiencies of proteins C and S and antithrombin III were evaluated by enzyme-linked immunosorbent assay (ELISA), dilute Russell Viper Venom time (dRVVT), coagulometric and chromogenic methods. DNA was amplified by the polymerase chain reaction (PCR) to study factor V Leiden and G20210A mutations in the prothrombin gene and C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Data were analyzed using odds ratios and a regression model for age adjustment. Fisher’s exact test was used to evaluate statistical relationships between associated factors and RSA. RESULTS: ACA was detected in 11 women with RSA and one fertile woman. Heterozygous C677T was detected in 59 women with RSA and 35 fertile women. Concomitant presence of ACA and C677T was found in eight women with RSA and no fertile women (p < 0.01). DISCUSSION: The meaning of the association between C677T mutation in the MTHFR gene and ACA is still not clear. It is possible that an inherited factor that alone would not strongly predispose a woman to thrombosis could, when associated with an acquired factor, start the process and increase the likelihood of thrombosis expression. CONCLUSIONS: ACA and C677T in the MTHFR gene are statistically associated with RSA. The association of these two conditions is a new finding in thrombogenic factors and RSA.

C677T Methylenetetrahydrofolate Reductase and Plasma Homocysteine Levels among Thai Vegans and Omnivores

2013 ◽  
Vol 83 (2) ◽  
pp. 86-91 ◽  
Author(s):  
Saowanee Kajanachumpol ◽  
Kalayanee Atamasirikul ◽  
Phieuvit Tantibhedhyangkul
Keyword(s):  
Vitamin B12 ◽  
Methylenetetrahydrofolate Reductase ◽  
Vitamin B12 Deficiency ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Serum Folate ◽  
Geometric Means ◽  
C677t Mutation ◽  
B12 Deficiency ◽  
Mthfr Mutation

Hyperhomocysteinemia among vegetarians and vegans is caused mostly by vitamin B12 deficiency. A C-to-T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene results in a thermolabile MTHFR, which may affect homocysteine (Hcy) levels. The importance of this gene mutation among populations depends on the T allele frequency. Blood Hcy, vitamin B12, folate, vitamin B6, and MTHFR C677T mutation status were determined in 109 vegans and 86 omnivores aged 30 - 50 years. The vegans had significantly higher Hcy levels than the omnivores, geometric means (95 % CI) 19.2 (17.0 - 21.7) µmol/L vs. 8.53 (8.12 - 8.95) µmol/L, p < 0.001. A C-to-T mutation in the vegans increased plasma Hcy, albeit insignificantly; geometric means 18.2 µmol/L, 20.4 µmol/L, and 30.0 µmol/L respectively in CC, CT, and TT MTHFR genotypes. There was also a significant decrease in serum folate; geometric means 12.1 ng/mL, 9.33 ng/mL, and 7.20 ng/mL respectively, in the CC, CT, and TT mutants, p = 0.006, and particularly, in the TT mutant compared with the CC wild type, 7.20 ng/mL vs. 12.1 ng/mL, p = 0.023. These findings were not seen in the omnivores. It was concluded that hyperhomocysteinemia is prevalent among Thai vegans due to vitamin B12 deficiency. C-to-T MTHFR mutation contributes only modestly to the hyperhomocysteinemia.

C677T MTHFR Mutation and Factor V Leiden Mutation in Patients with TIA/Minor Stroke

1999 ◽  
Vol 93 (2) ◽  
pp. 61-69 ◽  
Author(s):  
Wolfgang Lalouschek ◽  
Susanne Aull ◽  
Wolfgang Serles ◽  
Peter Schnider ◽  
Christine Mannhalter ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Minor Stroke ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
C677t Mthfr ◽  
Mthfr Mutation

Thrombophilic Genetic Mutations Have No Impact in the Pathogenesis of Thromboembolism in Gastro-Intestinal Cancer Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3518-3518
Author(s):  
Odoardo M. Olimpieri ◽  
Gaia Schiavon ◽  
Barbara Giannetti ◽  
Maria C. Tirindelli ◽  
Daniele Santini ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Gene Mutations ◽  
Factor V Leiden ◽  
Mthfr Gene ◽  
Intestinal Cancer ◽  
Genetic Mutations ◽  
Factor V ◽  
C677t Polymorphism ◽  
Factor Ii ◽  
C677t Mutation

Abstract Deep venous thrombosis and pulmonary embolism are well recognized and feared complications in cancer patients, with a considerable impact on the overall survival and the quality of life. During the last years many prothrombotic genetic mutations have been described, of these the most common are: Factor V Leiden, prothrombin G20210A gene mutation and the C677T mutation in the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene. Aim of this study was to asses the impact of these thrombophilic gene mutations on the development of VTE (Venous ThromboEmbolism) in patients with gastro-intestinal neoplasms. Moreover, we have tried to determine whether or not the C677T polymorphism of the MTHFR gene was associated with a higher toxicity during chemotherapy with antimetabolites such as 5-FU. From October 2002 to June 2004 48 patients (aged more than 18 years) not assuming anticoagulant therapy, with a new histopathologic diagnosis of gastro-intestinal cancer and no known hematologic or immunologic diseases were investigated by standard polymerase chain reaction techniques for the presence of the above thrombophilic gene mutations. Of the 48 tested patients, a homozygous or heterozygous Factor V Leiden was present respectively in 1 and 3, while the G20210A Factor II mutation was observed in 6 patients (all heterozygous). The C677T mutation in the MTHFR gene allelic frequency in the studied population was 46%. A VTE was observed in 7/48 patients (14.5%) and none of these patients had Factor V Leiden or G20210A Factor II mutations while 4 had a C677T MTHFR mutation. Therefore, none of the thrombophilic genetic mutations studied was associated to the development of VTE in the cohort of gastro-intestinal cancer patients. On the contrary chemotherapy (P=0.007) and advanced inoperable disease (P=0.009) were the only risk factors statistically significant for the development of VTE. As for toxicity during chemotherapy with antimetabolites, it was present in 25% of patients with the C677T polymorphism of the MTHFR while none of the patients without mutation had a toxicity (P=0.06). In conclusion, thrombophilic genetic mutations have no effect on the development of VTE in gastro-intestinal cancer patients. Moreover, we confirm that chemotherapy and an advanced disease play an important role in the pathogenesis of VTE in cancer patients. Furthermore, patients carrier of the C677T mutation in the MTHFR gene have a higher risk (OR: 1.4; C.I. 95%: 0.88–2.24) of toxicity during an antimetabolites-based chemotherapy.

scholarly journals Homozygous Cystathionine β-Synthase Deficiency, Combined With Factor V Leiden or Thermolabile Methylenetetrahydrofolate Reductase in the Risk of Venous Thrombosis

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 2015-2018 ◽  
Author(s):  
Leo A.J. Kluijtmans ◽  
Godfried H.J. Boers ◽  
Bert Verbruggen ◽  
Frans J.M. Trijbels ◽  
Irena R.O. Nováková ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Methylenetetrahydrofolate Reductase ◽  
Significant Risk ◽  
Factor V Leiden ◽  
Major Complication ◽  
Significant Risk Factor ◽  
Mthfr Gene ◽  
Factor V ◽  
Thromboembolic Complications ◽  
Thrombotic Complications

Abstract Severe hyperhomocysteinemia in its most frequent form, is caused by a homozygous enzymatic deficiency of cystathionine β-synthase (CBS). A major complication in CBS deficiency is deep venous thrombosis or pulmonary embolism. A recent report by Mandel et al (N Engl J Med 334:763, 1996) postulated factor V Leiden (FVL) to be an absolute prerequisite for the development of thromboembolism in patients with severe hyperhomocysteinemia. We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C→T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. Thrombotic complications were diagnosed in six patients, of whom only one was a carrier of FVL. On the contrary, thermolabile MTHFR caused by the 677C→T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR. These data indicate that FVL is not an absolute prerequisite and probably not even a major determinant of venous thrombosis in homocystinuria, but, interestingly, thermolabile MTHFR may constitute a significant risk factor for thromboembolic complications in this inborn error of methionine metabolism.

The Methylenetetrahydrofolate Reductase TT677 Genotype Is Associated with Venous Thrombosis Independently of the Coexistence of the FV Leiden and the Prothrombin

1998 ◽  
Vol 79 (05) ◽  
pp. 907-911 ◽  
Author(s):  
Maurizio Margaglione ◽  
Giovanna D’Andrea ◽  
Marina d’Addedda ◽  
Nicola Giuliani ◽  
Giuseppe Cappucci ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Methylenetetrahydrofolate Reductase ◽  
Factor V Leiden ◽  
Mthfr Gene ◽  
Factor V ◽  
Mthfr Genotype ◽  
Estimated Risk ◽  
Fv Leiden ◽  
Mild Hyperhomocysteinemia

SummaryA polymorphism, C→T677, in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified as a cause of mild hyperhomocysteinemia, a risk factor for venous thrombosis. We have investigated the frequency of the TT genotype in 277 consecutive patients with confirmed deep venous thrombosis and 431 healthy subjects. The TT MTHFR genotype was more frequent in patients than in controls (25.6% vs. 18.1%; p = 0.016). The risk of thrombosis among carriers of this genotype was significantly increased [odds ratio: 1.6 (95% CI: 1.1-2.3)]. The estimated risk associated with the TT genotype was 2.0 (95% CI: 1.3-3.1) in subjects with (n = 122), and 1.3 (95% CI: 0.8-2.0) in those without (n = 155) predisposing (hereditary, acquired or circumstantial) risk factors for venous thrombosis. Factor V Leiden and prothrombin G→A20210 are known risk factors for venous thrombosis. After stratification for FV Leiden and prothrombin A20210 mutations, a significant association was also observed. After adjustment for sex, FV Leiden and prothrombin A20210 mutation, the estimated risk of venous thrombosis among carriers of the TT MTHFR genotype was 1.7 (95% CI: 1.2-2.6). The TT MTHFR genotype is independently associated with venous thrombosis, mainly among individuals with a high risk profile.

Factor V Leiden, Prothrombin 20210 G → A and the MTHFR C677T Mutations in Childhood Stroke

1999 ◽  
Vol 81 (05) ◽  
pp. 690-694 ◽  
Author(s):  
E. A. Chalmers ◽  
A. Thomas ◽  
A. Sproul ◽  
C. Healey ◽  
I. Rafferty ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Protein S ◽  
Mthfr C677t ◽  
Anticardiolipin Antibodies ◽  
Mthfr Gene ◽  
Factor V ◽  
Large Prospective Study ◽  
C677t Mutation ◽  
Haematological Analysis

SummaryIschaemic stroke is a rare occurrence in children and in a proportion of cases the aetiology remains unknown. We have investigated the role of thrombophilia in the aetiology of this condition. Of 50 cases identified at two centres, 37 were available for detailed haematological analysis. No cases were identified with deficiencies of antithrombin, protein C or protein S. One case had elevated IgG anticardiolipin antibodies at low titre. The prevalence of the prothrombin 20210 G→A mutation, factor V Leiden (FVL) mutation and the C677T mutation in the MTHFR gene was compared in cases to that observed in random unselected cord blood controls. The odds ratio for stroke was not significantly increased in carriers of the prothrombin mutation (OR 1.2; 95% CI 0.1-10.7), FVL (OR 2.5; 95% CI 0.5-13.5), or the C677T mutation (OR 1.7; 95% CI 0.6-4.5). Our findings suggest that thrombophilia may not play a significant role in the aetiology of stroke in children, although a large prospective study is required to investigate this area further.

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