Ethnic Differences in the Frequency of the C677T Mutation in the Methylenetetrahydrofolate Reductase (MTHFR) Gene in Healthy Israeli Populations

The role of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene in retinal vein occlusion (RVO) is a theme of discussion since the first reports of RVO in patients with MTHFR C677T mutation and without classic acquired risk factors for retinal vascular disease. The association between MTHFR polymorphisms and RVO has been studied over the last 20 years producing conflicting results. This review aims to summarize the literature concerning the role MTHFR polymorphisms as risk factors for RVO.

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The Role of Vitamin B12 in Fasting Hyperhomocysteinemia and Its Interaction with the Homozygous C677T Mutation of the Methylenetetrahydrofolate Reductase (MTHFR) Gene

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613864 ◽

2000 ◽

Vol 83 (04) ◽

pp. 563-570 ◽

Cited By ~ 71

Author(s):

Antonio Coppola ◽

Pasquale Madonna ◽

Isabella Fermo ◽

Anna Pagano ◽

Giuseppina Mazzola ◽

...

Keyword(s):

Vitamin B12 ◽

Methylenetetrahydrofolate Reductase ◽

Phenotypic Expression ◽

Mthfr Gene ◽

Response To Treatment ◽

First Episode ◽

Mthfr Genotype ◽

C677t Mutation ◽

Folate And Vitamin B12 ◽

Ms Gene

SummaryTotal fasting plasma homocysteine (tHcy), homozygosity for the C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene and for the A2756G mutation of the methionine synthase (MS) gene, vitamin B12 and folate plasma levels were evaluated in 170 consecutive patients (89 M, 81 F; mean age 41 ± 12 yrs) with documented early-onset thrombosis (89 venous, 69 arterial, 12 both; mean age at first episode 36 ± 11 yrs), and in 182 age- and sex-matched healthy control subjects. Moderate hyperhomocysteinemia (HHcy, tHcy >19.5 µM in men and >15 µM in women) was detected in 45 patients (26.5%) and in 18 controls (9.9%, Mantel-Haenszel OR and 95% C.I. after stratification for arterial or venous thrombosis: 3.25, 1.78–5.91). The 677TT MTHFR genotype was not significantly more prevalent in patients (27.6%) than in controls (21.4%, RR = 1.42; 0.84–2.41), and markedly contributed to HHcy (Mantel-Haenszel RR after stratification for case/control status: 8.29, 4.61–14.9). The 2756GG MS genotype, observed in 4 patients (2.4%) and 8 controls (4.4%), was not associated to HHcy. tHcy was negatively correlated to folate and vitamin B12 levels, with better correlation found in subjects with the 677TT mutation (r = −0.42 and −0.25) than with the 677CC or CT MTHFR genotype (r = −0.37 and −0.11). However, folate was similar in patients and controls and vitamin B12 was higher in patients (460 ± 206 vs. 408 ± 185 pg/ml, p = 0.011). In a generalized linear model, 44% of the variation in tHcy levels was explained by folate and vitamin B12 levels, the MTHFR genotype, gender, and by the interaction of the MTHFR genotype with folate (p ≤0.028); the interactions of vitamin B12 with the MTHFR genotype, gender and patient/control status also significantly contributed to the variation in tHcy levels (p ≤0.028). A 4-week administration of 5-methyltetrahydrofolate (15 mg/day) markedly lowered plasma tHcy in 24 patients with MTHFR 677TT genotype, but the response to treatment correlated with vitamin B12 levels (p = 0.023). Subjects carrying the MTHFR 677TT genotype have higher folate and vitamin B12 requirements irrespective of the A2756G polymorphism of the MS gene. Yet unidentified abnormalities of MS or of any of the enzymes participating in the synthesis of methylated vitamin B12 may play an important role in the phenotypic expression of moderate hyperhomocysteinemia.

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Plasma total homocysteine levels and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene: a study in an Italian population with dementia

Mechanisms of Ageing and Development ◽

10.1016/s0047-6374(01)00307-4 ◽

2001 ◽

Vol 122 (16) ◽

pp. 2013-2023 ◽

Cited By ~ 35

Author(s):

Teodoro Bottiglieri ◽

Lucilla Parnetti ◽

Erland Arning ◽

Tanya Ortiz ◽

Serena Amici ◽

...

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Mthfr Gene ◽

Italian Population ◽

C677t Mutation ◽

Total Homocysteine ◽

Plasma Total Homocysteine

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

Sao Paulo Medical Journal ◽

10.1590/s1516-31802005000100004 ◽

2005 ◽

Vol 123 (1) ◽

pp. 15-20 ◽

Cited By ~ 9

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.

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Differences in the frequency of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene among the Lebanese population

American Journal of Hematology ◽

10.1002/ajh.20047 ◽

2004 ◽

Vol 76 (1) ◽

pp. 85-87 ◽

Cited By ~ 24

Author(s):

Wassim Y. Almawi ◽

Ramzi R. Finan ◽

Hala Tamim ◽

Jocelyn L. Daccache ◽

Noha Irani-Hakime

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Mthfr Gene ◽

Lebanese Population ◽

C677t Mutation

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

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000148 ◽

2013 ◽

Vol 83 (2) ◽

pp. 86-91 ◽

Cited By ~ 2

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.

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Factor V Leiden and Thermolabile Methylenetetrahydrofolate Reductase in Extreme Old Age

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665411 ◽

1997 ◽

Vol 78 (05) ◽

pp. 1357-1359 ◽

Cited By ~ 16

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.

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The C677T Mutation in the Methylenetetrahydrofolate Reductase (MTHFR) Gene and Vascular Dementia

Journal of the American Geriatrics Society ◽

10.1111/j.1532-5415.2000.tb04725.x ◽

2000 ◽

Vol 48 (6) ◽

pp. 664-668 ◽

Cited By ~ 33

Author(s):

Rivka Dresner Pollak ◽

Arthur Pollak ◽

Maria Idelson ◽

Idit Bejarano-Achache ◽

Dafna Doron ◽

...

Keyword(s):

Vascular Dementia ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr Gene ◽

C677t Mutation

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Prevalence of the MTHFR C677T Mutation in Fertile and Infertile Women

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics ◽

10.1055/s-0037-1606289 ◽

2017 ◽

Vol 39 (12) ◽

pp. 659-662 ◽

Cited By ~ 3

Author(s):

Adriana Soligo ◽

Ricardo Barini ◽

Joyce Annichino-Bizzacchi

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Mthfr Gene ◽

Control Group ◽

Case Group ◽

Infertile Women ◽

Chi Squared ◽

History Of ◽

C677t Mutation ◽

Fertile Women

Introduction The importance of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in infertile women remains controversial. Objective To evaluate if the MTHFR C677T mutations are more frequent in infertile women, and if they can be associated with the occurrence of infertility in the Brazilian population. Methods This case-control study included 130 infertile women consulting at a private clinic between March 2003 and March 2005 (data previously published), and 260 fertile women attending the family planning outpatient clinic of our institution between April 2012 and March 2013. Data analysis The Chi-squared and Fisher Exact tests were used to evaluate the association between the presence of the MTHFR C677T mutation and a history of infertility. Results The frequency of the mutation was of 58.5% for the case group (n = 76) and of 49.2% for the fertile controls (n = 128). The mutation was homozygous in 13 women in the case group (10%) and in 23 of the fertile women in the control group (8.8%). These differences were not statistically significant. Conclusions These results suggest that the presence of the MTHFR C677T mutation does not constitute a risk factor for infertility, even when the mutation is homozygous. Further studies are needed to confirm whether research on this mutation should be considered unnecessary in women with infertility.

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Semiautomated DNA Mutation Analysis Using a Robotic Workstation and Molecular Beacons

Clinical Chemistry ◽

10.1093/clinchem/47.4.739 ◽

2001 ◽

Vol 47 (4) ◽

pp. 739-744 ◽

Cited By ~ 14

Author(s):

Maarten L Smit ◽

Belinda A J Giesendorf ◽

Jacqueline A M Vet ◽

Frans J M Trijbels ◽

Henk J Blom

Keyword(s):

High Throughput ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr Gene ◽

Molecular Beacons ◽

Dna Mutation ◽

Increased Risk ◽

C677t Mutation ◽

Conventional Methods ◽

Robotic Workstation ◽

Edta Blood

Abstract Background: Our increasing knowledge of the genetic basis of inheritable diseases requires the development of automated reliable methods for high-throughput analyses. Methods: We investigated the combination of semiautomated DNA extraction from blood using a robotic workstation, followed by automated mutation detection using highly specific fluorescent DNA probes, so-called molecular beacons, which can discriminate between alleles with as little as one single-base mutation. We designed two molecular beacons, one recognizing the wild-type allele and the other the mutant allele, to determine genotypes in a single reaction. To evaluate this procedure, we examined the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, which is associated with an increased risk for cardiovascular disease and neural tube defects. DNA was isolated from 10 μL of fresh EDTA-blood samples by use of a robotic workstation. The DNA samples were analyzed using molecular beacons as well as conventional methods. Results: Both methods were compared, and no differences were found between outcomes of genotyping. Conclusions: The described assay enables robust and automated extraction of DNA and analysis of up to 96 samples (10 μL of blood per sample) within 5 h. This is superior to conventional methods and makes it suitable for high-throughput analyses.

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