scholarly journals Should MTHFR 1298 A>C be tested together with MTHFR 677 C>T polymorphism in women with reproductive challenges?

Genetika ◽  
2017 ◽  
Vol 49 (2) ◽  
pp. 377-386
Author(s):  
Jelena Djurovic ◽  
Oliver Stojkovic ◽  
Jelena Todorovic ◽  
Kristina Savic ◽  
Gorana Stamenkovic
Keyword(s):  
Genomic Dna ◽  
Methylenetetrahydrofolate Reductase ◽  
Critical Role ◽  
Mthfr Gene ◽  
Elevated Risk ◽  
Similar Frequency ◽  
Mthfr Polymorphisms ◽  
Healthy Female ◽  
Healthy Control ◽  
Associated Conditions

Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in the folate metabolism. The polymorphism 677C>T of the MTHFR gene, producing thermolabile enzyme with decreased function, is widely studied and associated with many conditions. Additionally, it has been shown that another polymorphism, 1298A>C, also reduces the activity of this enzyme, although to a lesser extent. The aim of this study is to evaluate the clinical informativeness of testing both MTHFR polymorphisms. Genomic DNA, were extracted from peripheral blood of 180 female patients with pregnancy complications and 183 healthy female controls, and genotyped for MTHFR 677C>T and 1298A>C loci, using TaqMan assays. Our study found similar frequency of alleles and genotypes between two groups. Based on MTHFR 677C>T genotype, 11.7% of patients homozygous for this mutation were under the possible risk. When the position 1298 was included in the testing, 22.8% of the patients were heterozygous for both polymorphisms. Additionally, 8.9% of the patients were homozygous only for the MTHFR 1298 mutation. Although,s there was no differences compared to healthy control (p>0.05), 43% of patients were found to have elevated risk which is about four time highers than results with only MTHFR 677C>T genotyping. After obtaining information for the 677 position, testing for the second polymorphism (1298A>C) should be considered, since we have shown that it dramatically increases the rate of detection of patients who are potentially at risk for MTHFR associated conditions.

scholarly journals Transmission Jeopardy of Adenomatosis Polyposis Coli and Methylenetetrahydrofolate Reductase in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Younis Mohd ◽  
Parvinder Kumar ◽  
Haripriya Kuchi Bhotla ◽  
Arun Meyyazhagan ◽  
Balamuralikrishnan Balasubramanian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Suppressor Gene ◽  
Mthfr Gene ◽  
Elevated Risk ◽  
Polyposis Coli ◽  
Chromosomal Alteration ◽  
Healthy Control ◽  
Variant Alleles

Colorectal cancer (CRC) is one of the globally prevalent and virulent types of cancer with a distinct alteration in chromosomes. Often, any alterations in the adenomatosis polyposis coli (APC), a tumor suppressor gene, and methylenetetrahydrofolate reductase (MTHFR) gene are related to surmise colorectal cancer significantly. In this study, we have investigated chromosomal and gene variants to discern a new-fangled gene and its expression in the southern populations of India by primarily spotting the screened APC and MTHFR variants in CRC patients. An equal number of CRC patients and healthy control subjects ( n = 65 ) were evaluated to observe a chromosomal alteration in the concerted and singular manner for APC and MTHFR genotypes using standard protocols. The increasing prognosis was observed in persons with higher alcoholism and smoking ( P < 0.05 ) with frequent alterations in chromosomes 1, 5, 12, 13, 15, 17, 18, 21, and 22. The APC Asp 1822Val and MTHFR C677T genotypes provided significant results, while the variant alleles of this polymorphism were linked with an elevated risk of CRC. Chromosomal alterations can be the major cause in inducing carcinogenic outcomes in CRCs and can drive to extreme pathological states.

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

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.

scholarly journals Evaluation of c677t and a1298c polymorphism of the methylenetetrahydrofolate reductase gene as a maternal risk factor for trisomy 21 (a monocentric study)

2017 ◽  
Vol 25 (1) ◽  
pp. 27-35
Author(s):  
Simona Bucerzan ◽  
Radu Anghel Popp ◽  
Raluca Maria Vlad ◽  
Cecilia Lazea ◽  
Radu Nicolaescu ◽  
...  
Keyword(s):  
Trisomy 21 ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Control Group ◽  
Healthy Children ◽  
Mthfr Polymorphisms ◽  
Maternal Risk ◽  
Reductase Gene ◽  
A1298c Polymorphism ◽  
Methylenetetrahydrofolate Reductase Gene

Abstract Aim: To assess the risk for trisomy 21 in children, depending on the polymorphisms C677T and A1298C of the methylenetetrahydrofolate reductase (MTHFR) gene in mothers. Methods: For 93 mothers who have children with trisomy 21 and 202 mothers of healthy children (control group), genotyping of MTHFR polymorphisms C677T and A1298C was performed. Results: For each polymorphism, three genotypes were identified (normal homozygous, heterozygous and mutant homozygous). For the polymorphism C677T, the frequencies of the three genotypes (CC, CT and TT) were 50.5%, 40.8% and 8.6% in mothers of children with trisomy 21, versus 42.6%, 46% and 11.4% in mothers of healthy children, with no statistically significant differences. The frequency of the polymorphism A1298C was not statistically significant between the two groups for the genotype (AA) (48.4% vs 56.4%) or the genotype (AC) (39.8% vs 38.6%), but the genotype TT was more frequent in mothers of children with trisomy 21 (11.8% vs 4.9%; p = 0.033; OR = 2.57). Conclusion: Women with genotype CC for the polymorphism A1298C of the MTHFR gene have a 2.57 times higher risk of offspring with trisomy 21.

Role of MTHFR genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia

Blood ◽  
2004 ◽  
Vol 103 (1) ◽  
pp. 252-257 ◽  
Author(s):  
Maja Krajinovic ◽  
Stéphanie Lamothe ◽  
Damian Labuda ◽  
Émilie Lemieux-Blanchard ◽  
Yves Théorêt ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Methylenetetrahydrofolate Reductase ◽  
Lymphoblastic Leukemia ◽  
Protective Role ◽  
Mthfr Gene ◽  
Environment Interaction ◽  
Crude Odds Ratio ◽  
Childhood All ◽  
Mthfr Polymorphisms

Abstract The central role of methylenetetrahydrofolate reductase (MTHFR) in the folate metabolism renders MTHFR gene polymorphisms (C677T and A1298C) potential modulators of a variety of disorders whose development depends on folate/homocysteine imbalance. Here, we provide additional evidence on the protective role of these polymorphisms in acute lymphoblastic leukemia (ALL), the most common pediatric cancer. A case-control study was conducted in 270 ALL patients and 300 healthy controls of French-Canadian origin. The TT677/AA1298 and CC677/CC1298 individuals were associated with reduced risk of ALL (crude odds ratio [OR] = 0.4; 95% confidence interval [CI], 0.2-0.9; and OR = 0.3; 95% CI, 0.1-0.6; respectively). Further stratification in patients born before and after January 1996 (approximate time of Health Canada recommendation for folic acid supplement in pregnancy) revealed that the protective effect of MTHFR variants is accentuated and present only in children born before 1996. Similar results were obtained when a transmission disequilibrium test was performed on a subset of children (n = 95) in a family-based study. This finding suggests gene-environment interaction and its role in the susceptibility to childhood ALL, which is consistent with previous findings associating either folate deficiency or MTHFR polymorphisms with risk of leukemia.

scholarly journals Effects of Ocufolin on retinal microvasculature in patients with mild non-proliferative diabetic retinopathy carrying polymorphisms of the MTHFR gene

2021 ◽  
Vol 9 (1) ◽  
pp. e002327
Author(s):  
Zhiping Liu ◽  
Hong Jiang ◽  
Justin H Townsend ◽  
Jianhua Wang
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Structural Changes ◽  
Methylenetetrahydrofolate Reductase ◽  
Vision Loss ◽  
Retinal Vessel ◽  
Mthfr Gene ◽  
Mthfr Polymorphisms ◽  
Retinal Microvasculature

IntroductionTo evaluate effects of Ocufolin on retinal microvasculature in mild non-proliferative diabetic retinopathy patients who carried methylenetetrahydrofolate reductase (MTHFR) polymorphisms (DR+MTHFRP).Research design and methodsThis is a prospective cohort study. Eight DR+MTHFRP (administrated Ocufolin for 6 months) and 15 normal controls (NCs) were recruited. MTHFR polymorphisms were subtyped as normal, C677T, or A1298C. Best-corrected visual acuity (BCVA) was evaluated. Retinal vessel density (VD) and microstructure were evaluated by optical coherence tomography angiography.ResultsBCVA and vascular indices of DR+MTHFRP at baseline were worse than those of NC and improved. Compared with baseline, DR+MTHFRP had significantly improved BCVA during follow-up period (p<0.05). VD of superficial vascular plexus was increased at 4 months (p=0.012), while VD of retinal vascular network did not change (p>0.05). Carriers of A1298C and C677T showed statistically significant increase in VD at all layers by 6 months, while carriers of C677T alone showed no significant change and carriers of A1298C alone showed decreased density from 4 months to 6 months. Microstructure did not change during the follow-up period.ConclusionA 6-month intake of Ocufolin is capable of reversing structural changes of microangiopathy in mild non-proliferative DR+MTHFRP. This suggests a novel way to address these impairments prior to catastrophic vision loss.

Folate, Homocysteine and Neural Tube Defects: An Overview

2001 ◽  
Vol 226 (4) ◽  
pp. 243-270 ◽  
Author(s):  
Nathalie M.J. Van Der Put ◽  
Henny W.M. Van Straaten ◽  
Frans J.M. Trijbels ◽  
Henk J. Blom
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Genetic Risk ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Folate Intake ◽  
Elevated Blood ◽  
Moderate Risk ◽  
Mthfr Polymorphisms ◽  
Increased Risk

Folate administration substantially reduces the risk on neural tube defects (NTD). The interest for studying a disturbed homocysteine (Hcy) metabolism in relation to NTD was raised by the observation of elevated blood Hcy levels in mothers of a NTD child. This observation resulted in the examination of enzymes involved in the folate-dependent Hcy metabolism. Thus far, this has led to the identification of the first and likely a second genetic risk factor for NTD. The C677T and A1298C mutations in the methylenetetrahydrofolate reductase (MTHFR) gene are associated with an increased risk of NTD and cause elevated Hcy concentrations. These levels can be normalized by additional folate intake. Thus, a dysfunctional MTHFR partly explains the observed elevated Hcy levels in women with NTD pregnancies and also, in part, the protective effect of folate on NTD. Although the MTHFR polymorphisms are only moderate risk factors, population-wide they may account for an important part of the observed NTD prevalence.

Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms of Both Donor and Recipient Can Modify the Rate of Recurrence in Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4933-4933
Author(s):  
So Yeon Oh ◽  
Hye Jin Kim ◽  
Hyeon Gyu Yi ◽  
Jin Won Kim ◽  
Cheng Zhe Piao ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Methylenetetrahydrofolate Reductase ◽  
Hematologic Malignancy ◽  
Univariate Analysis ◽  
Mthfr Gene ◽  
Hematopoietic Stem ◽  
Homogeneous Population ◽  
Mthfr Polymorphism ◽  
Mthfr Polymorphisms ◽  
Gvhd Prophylaxis

Abstract Introduction Clinical significance of polymorphism in MTHFR gene is widely described in various disease entities. Polymorphism is associated with decreased metabolism of methotrexate. Because methotrexate is commonly used to prevent GVHD in HSCT, we studied transplantation outcomes according to genotypes of donor and recipient MTHFR; about the most studied two polymorphism sites (677C/T and 1298A/C). Materials and Methods Patients and donors who underwent allogeneic HSCT due to hematologic malignancy between 1998 and 2006 were retrieved. Patients had received MTX and cyclosporine for GVHD prophylaxis were included. The genotyping of MTHFR polymorphism was screened using SNaPShot Multiplex kit. Clinical data were collected retrospectively. Results We found 99 patients consisted of 60 males (60%) and 39 females (39%) in this homogeneous population. Median age was 34 years (range17–59). Diagnosis were acute leukemia (n=67), chronic leukemia (n=20) and other diseases (n=12). Donor was related(n=72) or unrelated(n=27). Conditioning was myeloablative in 95 patients and nonmyeloablative in 4 patients. Median PFS and OS were 6 (range 0–101) and 15 (range 0–108) months. Clinical factors and genotype are analyzed for risk of hepatic toxicity, recurrence, TRM and death. Peak AST and ALT levels are higher in the 677TT group than in the CC or TT group. In univariate analysis, recipient or donor 1298AA, AC, and CC were likely to relapse in ascending orders (figure1). This was reproduced in multivariate analysis (p=0.008 and 0.011, for each). About TRM and survival, there were no significant correlations with MTHFR genotypes in both univariate and multivariate analysis. Conclusion Simultaneously decreased activity of MTHFR due to 1298AC polymorphism of both donor and recipient might be translated into increased recurrence rate. Validation with randomized trial is required to compare methotrexate to other drug for GVHD prophylaxis. Figure Figure

scholarly journals C677t (rs1801133 ) MTFHR gene polymorphism frequency in a colombian population

2015 ◽  
pp. 75-79 ◽  
Author(s):  
Consuelo Romero Sanchez ◽  
Alberto Gomez Gutierrez ◽  
Piedad Elena Gomez ◽  
María Consuelo Casas Gomez ◽  
Ignacio Briceño
Keyword(s):  
Microarray Data ◽  
Healthy Subjects ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Genetic Associations ◽  
Mthfr Polymorphisms ◽  
Increased Risk ◽  
Need To Evaluate ◽  
Genotype C ◽  
Therapeutic Alternatives

Introduction: Abnormal levels of the enzyme methylenetetrahydrofolate reductase (MTHFR) are associated with an increased risk of both cardiovascular and cerebrovascular disease and higher concentrations of homocysteine. Abnormal levels are also related to birth defects, pregnancy complications, cancer and toxicity to methotrexate (MTX). Polymorphisms of MTHFR affect the activity of the enzyme. Genetic associations have been related to treatment efficacy. Objective: To establish the frequency of the C> T polymorphism at nucleotide 677 of the MTHFR gene in a group of Colombian individuals. Methods: Data from pharmacogenetic microarrays that include MTX sensibility-associated polymorphisms were retrospectively collected (Pathway Genomics®). The frequency of the C> T MTHFR rs1801133 marker polymorphism was analyzed. Results: Microarray data from 68 men and 84 women were analyzed. Comparisons of genotype C/C vs. C/T and T/T were statistically significantly different (p= 0.00, p= 0.026, respectively), as were C/T and T / T (p= 0.0001). Conclusions: Results for the C/C and C/T genotypes in a Colombian population are similar to other previously studied groups of healthy subjects. Subjects from our population might be at risk of developing diseases associated with MTHFR polymorphisms and might present toxicity and adverse effects if treated with MTX, which suggests the need to evaluate therapeutic alternatives based on individual pharmacogenetic studies.

677TT Genotype Is Associated with Elevated Risk of Methotrexate (MTX) Toxicity in Juvenile Idiopathic Arthritis: Treatment Outcome, Erythrocyte Concentrations of MTX and Folates, and MTHFR Polymorphisms

2010 ◽  
Vol 37 (10) ◽  
pp. 2180-2186 ◽  
Author(s):  
JANA TUKOVÁ ◽  
JAROSLAV CHLÁDEK ◽  
MILOS HROCH ◽  
DANA NĚMCOVÁ ◽  
JOZEF HOZA ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Juvenile Idiopathic Arthritis ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Elevated Risk ◽  
Mthfr Polymorphisms ◽  
American College Of Rheumatology ◽  
Genotype Frequencies ◽  
Erythrocyte Concentration ◽  
677T Allele

Objective.To investigate whether methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and erythrocyte concentration of methotrexate (EMTX) could serve as predictors of methotrexate (MTX) efficacy and toxicity in patients with juvenile idiopathic arthritis (JIA).Methods.Genetic analyses and EMTX and folate assessment were performed in 69 patients with JIA aged 2.5–19.6 years (30 male) treated with MTX using a dose-escalation protocol and classified as full responders (disease inactivity; n = 51) or nonresponders (< 30% improvement in pediatric American College of Rheumatology-30 criteria while receiving ≥ 15 mg/m2/week parenteral MTX for at least 3 months; n = 18).Results.Nonresponders were treated with the higher median MTX dose (17.2 vs 12.6 mg/m2/week; p < 0.0001) and accumulated more EMTX (217 vs 106 nmol/l; p < 0.02) and erythrocyte folates (763 vs 592 nmol/l; p = 0.052) than responders. Analysis of MTHFR allele and genotype frequencies in relation to response failed to detect association. The frequency of any adverse effect was 29.4% in responders and 33.3% in nonresponders (p = 0.77). The frequency of 677T allele was elevated in patients with adverse effects (52.4% vs 20.9%; OR 3.88, 95% CI 1.8–8.6, p < 0.002). The probability of any adverse effect was significantly higher in patients with 677TT compared to the 677CC genotype (OR 55.5, 95% CI 2.9–1080, p < 0.001).Conclusion.MTHFR genotyping may have a predictive value for the risk of MTX-associated toxicity in patients with JIA. Despite the lack of therapeutic effect, nonresponders accumulated adequate concentrations of EMTX.

Association between Genetic Polymorphisms of 5,10-Methylenetetrahydrofolate Reductase and Cytokinesis-Block Micronucleus in Peripheral Blood Lymphocyte among 1,3-Butadiene Workers

2013 ◽  
Vol 273 ◽  
pp. 478-482
Author(s):  
Nan Liu ◽  
Xue Sheng Wang ◽  
Juan Cheng ◽  
Jing Wei Xiao ◽  
Bin Li
Keyword(s):  
Genetic Polymorphisms ◽  
Peripheral Blood ◽  
Methylenetetrahydrofolate Reductase ◽  
Peripheral Blood Lymphocytes ◽  
Mthfr Gene ◽  
Analysis Of Covariance ◽  
Chromosome Damage ◽  
Mthfr Polymorphisms ◽  
Gene Environment ◽  
Exposed Workers

Exploring the associations between genetic polymorphisms and susceptibility of chromosomal damage induced by 1,3-butadiene(BD) is of much importance for understanding BD carcinogenesis. In current study, we investigated the effects of MTHFR polymorphisms and MTHFR gene haplotype pairs on chromosome damage detected by the cytokinesis-block micronucleus (CBMN) assay in peripheral blood lymphocytes. The data showed that the frequencies of CBMN among BD-exposed workers were significantly associated with the MTHFR A1298C polymorphism (P=0.04 and P=0.03, respectively) by multivariate analysis of covariance. The foundings also showed that the haplotype pairs in the MTHFR gene were more likely than single SNPs to correlate with the BD-induced chromosome damage among occupational exposed workers. Gene-environment interactions between occupational BD exposure and polymorphisms of MTHFR were also evident. These results indicate that the MTHFR polymorphisms may play a role in sensitivity or genetic susceptibility in genotoxic effects of BD exposure in the occupational exposure population.

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