scholarly journals Effect of Methylenetetrahydrofolate Reductase (MTHFR) gene mutations and oxidative stress in silent brain infarction

2021 ◽  
Author(s):  
Pınar Aslan Koşar ◽  
Muhammet Yusuf Tepebaşı ◽  
Nihat Şengeze ◽  
İlter İlhan ◽  
Halil İbrahim Büyükbayram ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Brain Infarction ◽  
Gene Mutations ◽  
White Matter Lesions ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Total Thiol ◽  
Significant Difference ◽  
Silent Brain Infarction ◽  
Fazekas Scale

Abstract Ischemic infarctions occur under the influence of genetic and environmental factors. In our study, the role of ischemia-modified albumin and thiol balance, which are new markers in determining oxidative damage together with MTHFR gene mutations and homocysteine levels, in the development of SBI was investigated. White matter lesions in the magnetic resonance imaging (MRI) results of the patients were evaluated according to the Fazekas scale and divided into groups (Grade 0, 1, 2, and 3). Homocysteine, folate, B12, IMA, total thiol, and native thiol were measured by biochemical methods. The mutations in MTHFR genes were investigated by the RT-PCR method. According to our results, a significant difference was found between the groups in age, homocysteine, folate, IMA, total thiol, and native thiol parameters (p<0.05). When we compared the groups in terms of genotypes of the C677T gene, we found a significant difference in TT genotype between grades 0/3 and 1/3 (p<0.05). We determined that homocysteine and IMA levels increased and folate levels decreased in CC/TT and CT/TT genotypes in the C677T gene (p<0.05). Considering our results, the observation of homocysteine and IMA changes at the genotype level of the MTHFR C677T gene and between the groups, and the deterioration of thiol balance between the groups suggested that these markers can be used in the diagnosis of silent brain infarction.

scholarly journals Methylenetetrahydrofolate Reductase C677T and A1298C Mutations in Women with Recurrent Spontaneous Abortions in the Northwest of Iran

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ahmad Poursadegh Zonouzi ◽  
Nader Chaparzadeh ◽  
Mehrdad Asghari Estiar ◽  
Mahzad Mehrzad Sadaghiani ◽  
Laya Farzadi ◽  
...  
Keyword(s):  
Restriction Fragment Length Polymorphism ◽  
Methylenetetrahydrofolate Reductase ◽  
Fragment Length Polymorphism ◽  
Gene Mutations ◽  
Mthfr Gene ◽  
Amplification Refractory Mutation System ◽  
Healthy Controls ◽  
Significant Difference ◽  
Mutation System ◽  
Restriction Fragment Length

Introduction. Recurrent spontaneous abortion (RSA) is a significant obstetrical complication that may occur during pregnancy. Various studies in recent years have indicated that two common mutations (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene are risk factor for RSA. This study was carried out to determine the influence of (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene mutations with RSA. Materials and Methods. A total of 139 women were included in this study: 89 women with two or more consecutive miscarriages and 50 healthy controls. Total genomic DNA was isolated from blood leukocytes. To determine the frequency of the two common C677T and A1298C MTHFR gene mutations in the patients and controls, we used two methods, amplification refractory mutation system-PCR and PCR-restriction fragment length polymorphism. Results. There is no significant difference in the prevalence of 677T/T genotype among women with RSA and healthy controls (). Also no statistically significant difference in the frequency of A1298C MTHFR gene mutation was detected between the two groups ( ). Conclusion. In conclusion, the results indicate that the Amplification Refractory Mutation System-PCR method was in complete concordance with the results obtained by standard PCR-restriction fragment length polymorphism method. The results also show no significant difference in MTHFR C677T/A1298C genotype distribution among the two groups; therefore, further studies on larger population and other genetic variants to better understand the pathobiology of RSA are needed.

A case-control study investigating the effect of MTHFR C677T variant on performance of elite athletes

2020 ◽  
Vol 20 ◽  
Author(s):  
Ayse Feyda Nursal ◽  
Serbulent Yigit ◽  
Husniye Rustemoglu ◽  
Abdullah Cenikli
Keyword(s):  
Athletic Performance ◽  
Methylenetetrahydrofolate Reductase ◽  
Elite Athletes ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Control Group ◽  
Genotype Distribution ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Strength Of Association

Objective: Increased level of plasma homocysteine (Hcy) is a potential risk factor for several multi-system diseases. The Methylenetetrahydrofolate reductase (MTHFR) gene C677T variant has been established as an important genetic determinant of hyperhomocysteinemia. There are conflicting reports about the effects of physical activity on plasma Hcy. Therefore, the main aim of this study was to investigate whether the MTHFR C677T variant affects the elite athletic performance. Methods: This study was carried out on 214 individuals (114 elite athletes and 100 sedentary controls). Genotyping was performed using PCR- RFLP method. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Results: There was a significant difference between the athletes and the control group in genotype distribution and allele frequency of the MTHFR C677T variant. MTHFR C677T CC genotype and C allele were more prevalent in elite athletes than those in the sedentary controls (p =0.007, OR: 2.16, 95%:1.26-3.70; p=0.009, OR: 1.84, 95%:1.18-2.89, respectively). The control group had a higher MTHFR C677T CT genotype than the athletes had (p=0.019, OR: 0.51, 95%:0.30-0.88). There was no deviation from HWE for the MTHFR C677T variant in the groups. Conclusion: Our findings support that there is an association between the MTHFR C677T C allele and athletic performance among the elite Turkish athletes.

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)

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.

scholarly journals METHYLENETETRAHYDROFOLATE REDUCTASE C677T GENE POLYMORPHISM AND PROSTATE CANCER RISK

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.

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 Is MTHFR polymorphism a risk factor for Alzheimer's disease like APOE?

2005 ◽  
Vol 63 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Liana Lisboa Fernandez ◽  
Rosane Machado Scheibe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Methylenetetrahydrofolate Reductase ◽  
Venous Blood ◽  
Dna Amplification ◽  
Mthfr Gene ◽  
Chi Square ◽  
Mthfr Polymorphism ◽  
Significant Difference

BACKGROUND: The role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms as risk factors for the occurence of Alzheimer's disease (AD) is still controversial: OBJECTIVE: To verify the association between MTHFR and apolipoprotein E (APOE) polymorphisms and Alzheimer's disease. METHOD: This work was conducted as a case-control study. Cases included thirty patients with probable AD. Controls were constituted by 29 individuals without dementia according to neuropsychological tests paired to age, sex, race and educational level. DNA was isolated from peripheral leukocytes of anticoagulated venous blood. Genotyping of APOE and MTHFR were performed by DNA amplification and digestion. The frequences of APOE and MTHFR genotypes were submitted by chi-square test corrected by Fisher test; the APOE genotypes, to chi-square linear tendency test and the frequences of MTHFR mutant and AD, by stratificated anlysis adjust by Mantel-Haenszel method. RESULTS: There was significant difference about APOE4 and APOE2 in the groups. (p=0.002) The odds ratio increased exponentially with the increased number of E4 allele (chi2 linear tendency test). No significant difference was detected on MTHFR genotypes in both case and control groups. CONCLUSION: The APOE4 is a risk factor and demonstrated a dose-depenent effect while APOE2 allele conferred a protection to AD. The MTHFR mutation had no correlation with AD.

scholarly journals PREVALENCE OF MTHFR GENE 677C>T POLYMORPHISM IN THE PATIENTS WITH PSORIASIS VULGARIS

2021 ◽  
Vol 27 (2) ◽  
pp. 3707-3711
Author(s):  
Borislav Dimitrov ◽  
◽  
Dimitar Gospodinov ◽  
Veronika Gincheva ◽  
Regina Komsa-Penkova ◽  
...  
Keyword(s):  
Psoriasis Vulgaris ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Mthfr Polymorphism ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Pasi Score ◽  
Bulgarian Population ◽  
Relationship Of ◽  
The Relationship

The study aimed to investigate the relationship between carriage of 677C>T polymorphism in the gene of methylene tetrahydrofolate reductase (MTHFR) and plaque psoriasis in patients in Bulgaria. We examined the prevalence of MTHFR C677T genotype in patients with psoriasis, as well as the relationship of the polymorphism with disease severity. Our study covered63 patients with psoriasis and 98psoriasis-free control subjects from northern Bulgaria. MTHFR677C>T genotype was verified by the PCR-RFLP method. There was no significant difference between carriage of TT genotype among the patients and controls: 12.7% versus 10.8 %in controls, OR 1.203, (CI 95% 0465-3.175), p>0.05 respectively. There was a higher PASI score in patients, carriers of TT genotype of MTHFR polymorphism 677C>T than in non-carriers, 28.18versus 24.87 respectively, but not significant. Conclusion: Carriage of TT genotype of MTHFR polymorphism 677C>T was not associated with Psoriasis Vulgaris in the northern Bulgarian population when compared to healthy controls.

Phase I Clinical and Pharmacogenetic Trial of Irinotecan and Raltitrexed Administered Every 21 Days to Patients With Cancer

2001 ◽  
Vol 19 (20) ◽  
pp. 4081-4087 ◽  
Author(s):  
James P. Stevenson ◽  
Maryann Redlinger ◽  
Leo A.J. Kluijtmans ◽  
Weijing Sun ◽  
Kenneth Algazy ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Clinical Investigation ◽  
Performance Status ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Plasma Homocysteine ◽  
Gastrointestinal Malignancies ◽  
Patients With Cancer ◽  
Functional Polymorphisms

PURPOSE: Irinotecan and raltitrexed display schedule-dependent synergy in vitro, which supports the clinical investigation of the combination. Functional polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene result in intracellular redistribution of folate derivatives, which may affect raltitrexed-associated cytotoxicity.PATIENTS AND METHODS: Patients with a range of solid cancers and good performance status received irinotecan as a 90-minute infusion on day 1 and raltitrexed as a 15-minute infusion on day 2, repeated every 21 days. Samples were collected for MTHFR C677T genotyping and fasting plasma homocysteine during the first cycle.RESULTS: Thirty-nine assessable patients received 127 cycles of therapy. Irinotecan doses ranged from 100 to 350 mg/m2, and raltitrexed, 1.0 to 4.0 mg/m2. Raltitrexed doses of more than 3.0 mg/m2were not tolerated and were associated with dose-limiting asthenia, diarrhea, and AST/ALT elevation. Irinotecan/raltitrexed doses of 350/3.0 mg/m2were well-tolerated; principal toxicities included neutropenia, diarrhea, and fatigue. Two partial responses were observed in patients with pretreated gastroesophageal cancers. Homozygotes with the MTHFR 677 TT polymorphism incurred significantly less raltitrexed-associated toxicity than those with either wild-type or heterozygous genotypes (P = .05). No significant differences were noted in plasma homocysteine values between the genotypic subtypes, and plasma homocysteine levels did not predict the risk of toxicity.CONCLUSION: Irinotecan and raltitrexed doses of 350 and 3.0 mg/m2are recommended for further study on a day 1, 2 schedule every 21 days. Efficacy results suggest that trials in upper and lower gastrointestinal malignancies are warranted. MTHFR C677T genotypes may be predictive of clinical raltitrexed toxicity.

scholarly journals Genetic Mutations in Turkish Population With Pulmonary Embolism and Deep Venous Thrombosis

2010 ◽  
Vol 17 (6) ◽  
pp. E87-E94 ◽  
Author(s):  
Elif Kupeli ◽  
Hasibe Verdi ◽  
Abdullah Simsek ◽  
Fatma Belgin Atac ◽  
Fusun Oner Eyuboglu
Keyword(s):  
Allele Frequency ◽  
Methylenetetrahydrofolate Reductase ◽  
Health Hazard ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Turkish Population ◽  
Factor V ◽  
G20210a Mutation ◽  
Significant Difference ◽  
Pai 1

Venous thromboembolism (VTE) is a universal health hazard. Inherited and acquired risk factors increase the risk of VTE. We evaluated the relationship between factor V (G1691A, A1090G, and A1299G), prothrombin (PT G20210A), methylenetetrahydrofolate reductase (MTHFR C677T) mutations, plasminogen activator inhibitor 1 (PAI-1 -675) polymorphism, and VTE in Turkish population. In all, 80 patients with VTE and 104 controls were included. Heterozygous factor V Leiden (FVL) mutation was significantly higher among patients ( P = .04) with allele frequency of 6.3% ( P = .01). Heterozygous PT G20210A mutation was also significantly higher among patients ( P = .001) with allele frequency of 6.9% ( P = .003). MTHFR 677TT genotype was significantly higher in patients ( P = .009) with allele frequency of 23.8% ( P = .005). No significant difference was found in FV A1090G and FV A1299G mutation rate as well as PAI-1 genotypes and their allele frequencies ( P > .05). Thus, frequencies of FV G1691A, PT G20210A, and MTHFR C677T mutations are higher in patients with VTE. FV A1090G, FV A1299G mutations, and PAI-1 gene polymorphisms may not be a risk factor for VTE in Turkish population.

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