Methylenetetrahydrofolate Reductase Polymorphisms and Pregnancy Outcome

Abstract Introduction Aim of the study was to evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on pregnancy outcome. Materials and Methods A total of 617 pregnancies of women who were investigated for MTHFR C677T and A1298C polymorphisms prior to pregnancy were included in the study. Cases were classified into “homozygous polymorphisms” (Group I), “heterozygous polymorphisms” (Group II), and patients without polymorphisms who functioned as controls (Group III). Patients with polymorphisms were assigned to a specific protocol at least 3 months before becoming pregnant. Administration of low molecular weight heparin (LMWH) was started very early during pregnancy. The Beksac Obstetrics Index (BOI) was used to estimate the obstetric risk levels for the different groups. Results We found that the early pregnancy loss (EPL) rate increased as MTHFR polymorphism complexity increased and that the early EPL rate was significantly higher in patients with MTHFR C677T polymorphism compared to patients with MTHFR A1298C polymorphism (p = 0.039). There were significant differences between the previous pregnancies of the patients in the 3 study groups in terms of perinatal complications and EPLs (p = 0.003 and p = 0.019). The BOI decreased as the severity of polymorphisms increased. An association between MTHFR polymorphisms and congenital malformations and chromosomal abnormalities was observed. We could not demonstrate any statistically significant difference between study groups when the 3 groups were compared with regard to the pregnancy outcomes under specific management protocols. Conclusion MTHFR polymorphisms are potential risk factors for adverse pregnancy outcomes.

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TS and MTHFR gene polymorphisms in patients (pts) with recurrent or metastatic squamous cell carcinoma of the head or neck (SCCHN) treated with pemetrexed (P) and bevacizumab (B)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e17011 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e17011-e17011

Author(s):

M. Romkes ◽

T. M. Feinstein ◽

S. Zhong ◽

S. Buch ◽

M. K. Gibson ◽

...

Keyword(s):

Overall Survival ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Mthfr Gene ◽

Trend Test ◽

Sequence Detection ◽

Mthfr Polymorphism ◽

Detection Systems ◽

Pcr Product ◽

Significant Difference

e17011 Background: P inhibits multiple enzymes in folate metabolism. We examined polymorphisms in thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) in patients with SCCHN treated in a phase II clinical trial with P and B (ASCO 2008; A6069). Methods: All pts were treated with P 500 mg/m2 and B 15 mg/kg, given IV every 21 days until progression. Primary endpoint was time to progression (TTP). DNA was isolated from whole blood samples using commercially available kits. Polymorphisms examined were MTHFR (C677T, A1298C and G1793A) and TS (TS2R3R, TSG2RG and TSmut6). The MTHFR SNPs were detected using TaqMan based SNP genotyping kits from Applied Biosystems, run on the ABI Prism 7700 Sequence Detection systems v 1.7 (Foster City, CA). The TS promoter repeat and promoter SNP polymorphisms and the 3’ untranslated region 6 bp deletion polymorphism were determined using published methods to detect PCR product size and RFLP-PCR assays respectively. Results: 22 pts were genotyped from 34 enrolled. There was no significant difference in characteristics between pts with and without genotype data. For the MTHFR polymorphism C677T, there was a trend towards decreased disease control rate (DCR) (CR/PR/SD) (p = 0.058, Jonckheere-Terpstra trend test) and worse TTP (p = 0.04) transitioning from variant CC to CT to TT; comparing TT genotype versus CT and CC combined, pts with TT had inferior DCR (p = 0.03) and TTP (p = 0.0003); homozygotes with TT had a median TTP of 2.6 months (mo) 95% CI (1.4, NA) versus 5.6 mo (4.2, 11.4) for pts with CT or CC variants. For the MTHFR A1298C SNP, there was no significant difference in DCR between variants, median TTP for homozygotes pts with AA was 4.1 mo (2.6, NA) vs. 6.7 mo (5.1, NA) in pts with AC or CC variants (p = 0.084); median overall survival for AA was 10.2 mo (7.6, NA) and for AC or CC 17.6 mo (17, NA) (p = 0.045). The MTHFR G1793A and TS polymorphisms did not impact DCR, TTP or overall survival. There was no association between any polymorphism and the incidence of grade >2 toxicities. Conclusions: Polymorphisms in MTHFR are potentially associated with antitumor efficacy of P-based therapy in recurrent or metastatic SCCHN. These results warrant validation in larger studies with P in SCCHN. No significant financial relationships to disclose.

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METHYLENETETRAHYDROFOLATE REDUCTASE C677T GENE POLYMORPHISM AND PROSTATE CANCER RISK

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i5.24390 ◽

2018 ◽

Vol 11 (5) ◽

pp. 387

Author(s):

Samah Tellouche-bouhouhou ◽

Djalila Chellat-rezgoune ◽

Noureddine Abadi ◽

Dalila Satta ◽

Abderrezak Dahdouh

Keyword(s):

Prostate Cancer ◽

Methylenetetrahydrofolate Reductase ◽

Cancer Susceptibility ◽

Prostate Cancer Risk ◽

Mthfr C677t ◽

Mthfr Gene ◽

Single Nucleotide ◽

Mthfr C677t Polymorphism ◽

Increased Risk ◽

Significant Difference

Objective: The single nucleotide polymorphism C677T of the methylenetetrahydrofolate reductase (MTHFR) gene encodes a thermolabile enzyme. This polymorphism was found to be implicated in cancer susceptibility. In this study, we analyzed the distribution of the MTHFR C677T polymorphism in two cohorts; patients and controls native of East of Algeria to explore the possible association between this polymorphism and prostate cancer susceptibility.Methods: Our examination has been conducted in 98 cases and 98 healthy controls. Genotyping was realized by polymerase chain reaction-restriction fragment length polymorphism method.Results: Compared with CC homozygous, the CT heterozygous was found to have a significantly increased risk of prostate cancer (p=0.04; odds ratio [OR]=2.01, 95% confidence interval [CI]: 1.02–3.95). However, no statistically significant difference was observed concerning the TT homozygous (p=0.74; OR=1.25, 95% CI: 0.51–3.04).Conclusion: Our results indicate that the genotype CT is a risk factor for prostate cancer in East of Algeria.

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Association of MTHFR C677T and A1298C Polymorphisms with Susceptibility to Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis

Iranian Journal of Public Health ◽

10.18502/ijph.v50i1.5074 ◽

2021 ◽

Author(s):

Atefeh RAOUFI ◽

Behdad RAHIMI KELARIJANI ◽

Hamid Reza AHADI ◽

Bahareh HASSANI DERAKHSHANDEH ◽

Zahra NOOROOLLAHZADEH ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Methylenetetrahydrofolate Reductase ◽

Meta Analysis ◽

Mthfr C677t ◽

Gene Interaction ◽

Lymphocytic Leukemia ◽

Mthfr Polymorphism ◽

Mthfr Polymorphisms ◽

Comprehensive Search ◽

Allelic Model

Background: The relation between methylenetetrahydrofolate reductase)MTHFR( polymorphisms and the risk of developing Chronic lymphocytic leukemia (CLL) is not still clear, while there are reports about the association of MTHFR C677T and A1298C polymorphisms with developing CLL, there are other reports that rolled out the association of MTHFR polymorphisms with developing CLL. Therefore herein we carried out this meta-analysis to clear the association of MTHFR polymorphisms with the risk of CLL Methods: A comprehensive search was performed through PubMed, Scopus and Embase from inception to Aug 2020. Odds ratios (OR) with their corresponding 95% confidence intervals (CI) for five possible genetic models were calculated. Heterogeneity was evaluated using the Cochran Q test and the I2 statistic. Results: Totals of 1290 cases and 1887 controls for the C677T polymorphism and 1117 cases and 1256 controls for the A1298C polymorphism were included in our analysis. Analyzing the MTHFR C677T and A1298C polymorphisms genotypes showed an association between MTHFR polymorphism at A1298C under Allelic model and the risk of CLL (OR = 1.12, 95% CI = 1.01–1.25), however there was no association between MTHFR polymorphism at MTHFR C677T and risk of CLL. Conclusion: The risk of developing CLL might be associated with MTHFR polymorphism at A1298C under allelic model and not associated with MTHFR polymorphisms at C677T, However, further studies considering other factors such as age, gender, ethnicity, gene-gene interaction and environmental condition are needed to clear the true association of MTHFR polymorphisms with CLL.

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Postgraduate Symposium The MTHFR C677T polymorphism, B-vitamins and blood pressure

Proceedings of The Nutrition Society ◽

10.1017/s0029665109991728 ◽

2009 ◽

Vol 69 (1) ◽

pp. 156-165 ◽

Cited By ~ 20

Author(s):

C. P. Wilson ◽

H. McNulty ◽

J. M. Scott ◽

J. J. Strain ◽

M. Ward

Keyword(s):

Blood Pressure ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Mthfr Gene ◽

B Vitamins ◽

Vitamin B ◽

C677t Polymorphism ◽

Mthfr Polymorphism ◽

Mthfr C677t Polymorphism ◽

B Vitamin

High blood pressure (BP) and elevated homocysteine are reported as independent risk factors for CVD and stroke in particular. The main genetic determinant of homocysteine concentrations is homozygosity (TT genotype) for the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, typically found in approximately 10% of Western populations. The B-vitamins folate, vitamin B12and vitamin B6are the main nutritional determinants of homocysteine, with riboflavin more recently identified as a potent modulator specifically in individuals with the TT genotype. Although observational studies have reported associations between homocysteine and BP, B-vitamin intervention studies have shown little or no BP response despite decreases in homocysteine. Such studies, however, have not considered the MTHFR C677T polymorphism, which has been shown to be associated with BP. It has been shown for the first time that riboflavin is an important determinant of BP specifically in individuals with the TT genotype. Research generally suggests that 24 h ambulatory BP monitoring provides a more accurate measure of BP than casual measurements and its use in future studies may also provide important insights into the relationship between the MTHFR polymorphism and BP. Further research is also required to investigate the association between specific B-vitamins and BP in individuals with different MTHFR genotypes in order to confirm whether any genetic predisposition to hypertension is correctable by B-vitamin intervention. The present review will investigate the evidence linking the MTHFR C677T polymorphism to BP and the potential modulating role of B-vitamins.

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Superficial thrombophlebitis in varicose vein disease: the particular role of methylenetetrahydrofolate reductase

Phlebology The Journal of Venous Disease ◽

10.1258/phleb.2009.009075 ◽

2010 ◽

Vol 26 (4) ◽

pp. 135-139 ◽

Cited By ~ 8

Author(s):

C Wilmanns ◽

A Casey ◽

H Schinzel ◽

P K Walter

Keyword(s):

Varicose Vein ◽

Methylenetetrahydrofolate Reductase ◽

Protein S ◽

Mthfr C677t ◽

Factor V ◽

Mthfr C677t Polymorphism ◽

Mthfr Polymorphisms ◽

Vein Thrombosis ◽

Deep Vein ◽

Vein Disease

Background The purpose of this study was to compare the genetic background of superficial (SVT) and deep vein thrombosis (DVT). Methods Factor V (FV)-Leiden (G16891A)-, factor II(G20210A)-mutations, protein C- and S, as well as methylenetetrahydrofolate reductase (MTHFR) polymorphisms at C677T and A1298C, and serum homocysteine levels (hcy) were determined in 29 patients with SVT and 26 with DVT. Findings FV- and –II-mutations were less frequent in patients with SVT (2/3) compared with DVT (9/5), respectively ( P < 0.002 in case of FV). However, the frequency of the MTHFR C677T polymorphism was significantly higher in patients with SVT compared with DVT (CT 12 versus 10, and TT 7 versus 1, respectively, P << 0.001). The distribution of the MTHFR A1298C genotype and serum hcy levels was similar in both patient groups. Protein S-deficiency was recorded once (SVT). Interpretation These results suggest that the MTHFR C677T-mutant genetically predisposes its carriers to SVT which may contribute to hypercoagulation in pre-existing varicose vein disease.

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Methylenetetrahydrofolate Reductase C677T Gene Polymorphism as a Risk Factor for Hypertension in a Rural Population

International Journal of Hypertension ◽

10.1155/2020/4267246 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Rony Mario Candrasatria ◽

Suko Adiarto ◽

Renan Sukmawan

Keyword(s):

Gene Polymorphism ◽

Risk Stratification ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Geographic Region ◽

Taqman Assay ◽

Mthfr C677t Polymorphism ◽

Mutant Genotype ◽

Public Health Burden ◽

Significant Difference

Hypertension remains a public health burden despite advances in its management. Hence, the search for further risk stratification tools and prevention and new treatment approaches continues. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with hypertension. Interestingly, riboflavin, as a cofactor of MTHFR, may control blood pressure in patients with mutant MTHFR variants. These double benefits of a risk stratification tool and treatment approach make it interesting. Because this polymorphism depends on ethnicity and geographic region, we aimed to determine the association between MTHFR C677T gene polymorphism and hypertension in a rural Indonesian-Sundanese population. This population-based case-control study included 213 hypertensive subjects and 202 nonhypertensive subjects as controls. The TaqMan assay was used to determine the MTHFR C677T genotypes. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the risk of association. There was a significant difference in MTHFR C677T allele frequencies between the hypertensive and control groups (62.9% CC, 34.3% CT, 2.8% TT vs. 77.7% CC, 20.8% CT, 1.5% TT; p=0.004) and between mutant (TT and CT) and wild-type genotypes (CC) (p=0.001). The mutant genotype was associated with a risk of hypertension (OR 2.1; 95% CI 1.3–3.5) when adjusted for age, body mass index, waist circumference, and diabetes mellitus. The mutant of the MTHFR C677T gene increases the risk of hypertension in rural Indonesian-Sundanese population. These findings may be used in future studies to evaluate the effect of riboflavin supplementation in this population.

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Methylenetetrahydrofolate reductase C677T polymorphism and toxicity to 5-FU-based chemotherapy in colorectal cancer

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i1.30 ◽

2020 ◽

Vol 19 (1) ◽

pp. 209-213

Author(s):

Yong-lian Zhang ◽

Xiong-wei Xie

Keyword(s):

Colorectal Cancer ◽

Methylenetetrahydrofolate Reductase ◽

Direct Sequencing ◽

Skin Toxicity ◽

Mthfr C677t ◽

C677t Polymorphism ◽

Mthfr Polymorphism ◽

Mthfr C677t Polymorphism ◽

C677t Mutation ◽

Hematopoietic Toxicity

Purpose: To investigate the toxicity of methylenetetrahydrofolate reductase (MTHFR) polymorphism in colorectal cancer patients treated with 5-fluorouracil (5-FU).Methods: A total of 105 patients with colorectal cancer who underwent 5-FU therapy were included in this study. MTHFR C677T polymorphisms were determined using direct sequencing. Physical examination and the results of blood and urine tests were used to evaluate the toxicities, including gastrointestinal toxicity, hematopoietic toxicity, hair-skin toxicity and hand-foot syndrome.Results: In 90.5 % of all patients, 5-FU toxicity was observed. With regard to MTHFR C677T mutation, 45.7 % heterozygote mutants and 19.0 % homozygote mutants were observed. MTHFR C677T polymorphism was statistically related to 5-FU toxicity (p = 0.000). In addition, MTHFR C677T mutation was closely related to hematopoietic toxicity (p = 0.005).Conclusion: MTHFR C677T can be used for the prediction of 5-FU toxicity, and can also predict hematopoietic toxicity in patients with colorectal cancer. Keywords: MTHFR genes, Polymorphism, Colorectal cancer, Biomarker, Toxicity

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MTHFR T677 Homozygosis Influences the Presence of Aura in Migraineurs

Cephalalgia ◽

10.1111/j.1468-2982.2004.00692.x ◽

2004 ◽

Vol 24 (6) ◽

pp. 491-494 ◽

Cited By ~ 60

Author(s):

A Oterino ◽

N Valle ◽

Y Bravo ◽

P Muñoz ◽

P Sánchez-Velasco ◽

...

Keyword(s):

Genetic Risk ◽

Migraine Without Aura ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Healthy Controls ◽

Mthfr Polymorphism ◽

Mthfr C677t Polymorphism ◽

Genotypic Distribution ◽

C677t Mthfr ◽

Migraine Pathogenesis

It has been suggested that folate metabolism could be involved in migraine pathogenesis. We analysed the 5′, 10′ -methylenetetrahydrofolate reductase (MTHFR) genotypic distribution in a large migraine sample. We genotyped 230 migraine patients (152 migraine without aura (MO) and 78 migraine with aura (MA)) and 204 nonheadache controls. The incidence of TT homozygosis for migraine in general (12%), MO (9%) and MA (18%) did not significantly differ from that found in healthy controls (13%). Differences were significant when the frequency of TT homozygosis between MA and MO ( P = 0.03, OR = 2.34, 95% CI = 1.04-5.26) was compared. There was a tendency for a higher frequency of the MTHFR T allele in the MA group (42%) as compared to MO (29%) and controls (36%). These differences were significant only in the case of MA vs. MO ( P = 0.006, OR = 1.75, 95% CI = 1.15-2.65). These results could indicate that the MTHFR C677T polymorphism, causing mild hyperhomocystinaemia, might be a genetic risk factor for experiencing aura among migraineurs. Overall, however, there was no association between migraine and the C677T MTHFR polymorphism.

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Methylenetetrahydrofolate reductase polymorphisms as risk factors for retinal venous occlusive disease: A literature review

European Journal of Ophthalmology ◽

10.1177/11206721211000647 ◽

2021 ◽

pp. 112067212110006

Author(s):

Manuel Marques ◽

Francisco Alves ◽

Miguel Leitão ◽

Catarina Rodrigues ◽

Joana Tavares Ferreira

Keyword(s):

Risk Factors ◽

Literature Review ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Mthfr Gene ◽

Mthfr Polymorphisms ◽

Vein Occlusion ◽

C677t Mutation ◽

Retinal Vascular Disease

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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