Biochemical Studies of Human Methionine Synthase Reductase

2002 ◽  
pp. 537-542
Author(s):  
H. Olteanu ◽  
R. Banerjee
Keyword(s):  
Methionine Synthase ◽  
Methionine Synthase Reductase ◽  
Biochemical Studies

scholarly journals Haplotype analysis of the folate-related genes MTHFR, MTRR, and MTR and migraine with aura

Cephalalgia ◽  
2013 ◽  
Vol 33 (7) ◽  
pp. 469-482 ◽  
Author(s):  
Kathryn A Roecklein ◽  
Ann I Scher ◽  
Albert Smith ◽  
Tamara Harris ◽  
Gudny Eiriksdottir ◽  
...  
Keyword(s):  
Migraine With Aura ◽  
Multiple Testing ◽  
Haplotype Analysis ◽  
Methylenetetrahydrofolate Reductase ◽  
Population Based ◽  
Methionine Synthase ◽  
Association Testing ◽  
Methionine Synthase Reductase ◽  
Increased Risk ◽  
Genes Encoding

Aims The C677T variant in the methylenetetrahydrofolate reductase ( MTHFR; EC 1.5.1.20) enzyme, a key player in the folate metabolic pathway, has been associated with increased risk of migraine with aura. Other genes encoding molecular components of this pathway include methionine synthase ( MTR; EC 2.1.1.13) and methionine synthase reductase ( MTRR; EC 2.1.1.135) among others. We performed a haplotype analysis of migraine risk and MTHFR, MTR, and MTRR. Methods Study participants are from a random sub-sample participating in the population-based AGES-Reykjavik Study, including subjects with non-migraine headache ( n = 367), migraine without aura ( n = 85), migraine with aura ( n = 167), and no headache ( n = 1347). Haplotypes spanning each gene were constructed using Haploview. Association testing was performed on single SNP and haplotypes using logistic regression, controlling for demographic and cardiovascular risk factors and correcting for multiple testing. Results Haplotype analysis suggested an association between MTRR haplotypes and reduced risk of migraine with aura. All other associations were not significant after correcting for multiple testing. Conclusions These results suggest that MTRR variants may protect against migraine with aura in an older population.

Association of homocysteine (but not of MTHFR 677 C>T, MTR 2756 A>G, MTRR 66 A>G and TCN2 776 C>G) with ischaemic cerebrovascular disease in Sicily

2006 ◽  
Vol 96 (08) ◽  
pp. 154-159 ◽  
Author(s):  
Rosa-Maria Guéant-Rodriguez ◽  
Guido Anello ◽  
Rosario Spada ◽  
Antonino Romano ◽  
Adrian Fajardo ◽  
...  
Keyword(s):  
Cerebrovascular Disease ◽  
Vitamin B12 ◽  
Methylenetetrahydrofolate Reductase ◽  
Methionine Synthase ◽  
Italian Population ◽  
Significant Independent Predictor ◽  
Methionine Synthase Reductase ◽  
Ischaemic Cerebrovascular Disease ◽  
Folate And Vitamin B12 ◽  
Neutral Effect

SummaryAssociation between methylenetetrahydrofolate reductase polymorphism (MTHFR 677 C>T), a determinant of homocysteine plasma level (t-Hcys), with ischaemc cerebrovascular disease (iCVD) seems to be neutral in North Europe and North America. The association of 2756 A>G of methionine synthase (MTR), 66 A>G of methionine synthase reductase (MTRR) and 776 C>G of transcobalamin (TCN2) needs to be evaluated further. It was the objective of this study to evaluate the association of these polymorphisms, t-Hcys, vitamin B12 and folate levels with iCVD, in an Italian population from Sicily. We investigated the association of these polymorphisms, t-Hcys, vitamin B12 and folate with iCVD in 252 subjects, including 131 cases and 121 sexand agematched healthy controls. t-Hcys was higher in the iCVD group than in controls [15.3 (11.5–17.9) vs. 11.6 (9.4–14.5) µM; P=0. 0007] and also in subjects withTCN2 776CG genotype, compared to homozygous genotypes [13.5 (9.9± 16.9) vs. 11.7 (9.6 ± 14.4) µM; P=0. 0327]. The folate level in cases and controls was consistent with an adequate dietary intake [12.7 (9.0–15.3) vs. 12.5 (9.6–16.9) nM; P=0. 7203]. In multivariate analysis, t-Hcys was a significant independent predictor of iCVD with an odds ratio of 1.14 (95% C.I. : 1.06–1.24; P=0. 0006). No association was found between MTHFR, MTR, MTRR and TCN2 polymorphisms and iCVD risk. We have found an influence of t-Hcys and a neutral effect of MTHFR, MTR, MTRR and TCN2 on iCVD risk in Sicily. The neutral influence of these polymorphisms may be explained by adequate status in folate and vitamin B12. Other factors underlying the increased t-Hcys need further investigations.

scholarly journals Factors associated with rs1801394 of the methionine synthase reductase gene polymorphism in patients with rheumatoid arthritis

2021 ◽  
Vol 15 (3) ◽  
pp. 15-19
Author(s):  
M. Yu. Krylov ◽  
G. I. Gridneva ◽  
Yu. V. Muravyev
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Characteristics ◽  
Methionine Synthase ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination ◽  
Methionine Synthase Reductase ◽  
Reductase Gene ◽  
Group 2 ◽  
The Relationship ◽  
Group 1

Clinical response to methotrexate (MT) therapy in rheumatoid arthritis (RA) can be predicted on the basis of some single nucleotide polymorphisms (SNPs) of genes, involved in folate metabolism. One of these SNPs is the rs1801394 (A66G) polymorphism of the methionine synthase reductase gene (MTRR). We investigated the association of this polymorphism with the clinical characteristics of RA patients after 6 months of MT therapy. Studies of the relationship between the response to MT therapy and the rs1801394 polymorphism have not been carried out in Russia previously.Objective: to study the possible association of the rs1801394 polymorphism with the clinical characteristics of patients with RA after 6 months of MT therapy.Patients and methods. The study included 60 patients with RA who met the ACR / EULAR criteria (2010) and received≥20 mg MT per week continuously. Based on the EULAR criteria, patients were divided into two groups: group 1 (n=30) with a good (DAS28>1.2) and group 2 (n=30) with an unsatisfactory (DAS28 <1.2) response to MT therapy. Genotyping of the rs1801394 polymorphism was performed by allelic discrimination using real-time polymerase chain reaction.Results and discussion. The frequency distribution of the A66G polymorphism genotypes in both groups was similar, however, in the 2nd group with an unsatisfactory response, there was a tendency towards a higher frequency of the mutant GG genotype (p=0.067). An association of the A66G polymorphism with gender and disease duration was found. In group 1, the AG genotype was more often detected in men than in women (p=0.017). In group 2, the AG genotype was also more common in men (p=0.075). In addition, in this group, carriers of the G allele (genotypes AG and GG) had a longer duration of the disease than carriers of the AA genotype (p=0.003 and p=0.005, respectively).Conclusion. In the present study, the relationship of the studied polymorphism rs1801394 of the MTRR gene with gender and duration of RA disease was established.

Polymorphic background of methionine synthase reductase modulates the phenotype of a disease-causing mutation

2007 ◽  
Vol 28 (10) ◽  
pp. 1028-1033 ◽  
Author(s):  
Carmen Gherasim ◽  
David S. Rosenblatt ◽  
Ruma Banerjee
Keyword(s):  
Methionine Synthase ◽  
Methionine Synthase Reductase

The relationship between methionine synthase rs1805087 polymorphism and hematological cancers risk

2020 ◽  
Vol 16 (28) ◽  
pp. 2219-2233
Author(s):  
Yanliang Bai ◽  
Emmanuel Kwateng Drokow ◽  
Hafiz Abdul Waqas Ahmed ◽  
Juanjuan Song ◽  
Gloria Selorm Akpabla ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Cancer Susceptibility ◽  
Meta Analysis ◽  
Recessive Model ◽  
Methionine Synthase ◽  
Hematological Cancer ◽  
Methionine Synthase Reductase ◽  
Hematological Cancers ◽  
The Relationship ◽  
Allele Model

Background: The relationship between hematological cancer susceptibility and methionine synthase MTR A2756G (rs1805087) polymorphism is inconclusive based on data from past studies. Hence, this updated meta-analysis was conducted to investigate the relationship between methionine synthase reductase (MTR) rs1805087 polymorphism and hematological cancers. Method: We searched EMBASE, Google Scholar, Ovid and PubMed databases for possible relevant articles up to December 31, 2019. Results: The overall pooled outcome of our analysis showed lack of association between the risk of hematological malignancies and MTR A2756G polymorphism under the allele model (G vs A: odds ratio = 1.001, 95% CI: 0.944–1.061; p = 0.983), recessive model (GG vs GA + AA: odds ratio = 1.050, 95% CI: 0.942–1.170; p = 0.382). Conclusion: The findings in this study demonstrate a lack of relationship between hematological cancers and MTR A2756G.

scholarly journals Vitamin B-12 and liver activity and expression of methionine synthase are decreased in fetuses with neural tube defects

2019 ◽  
Vol 109 (3) ◽  
pp. 674-683
Author(s):  
Ma'atem B Fofou-Caillierez ◽  
Rosa-Maria Guéant-Rodriguez ◽  
Jean-Marc Alberto ◽  
Céline Chéry ◽  
Thomas Josse ◽  
...  
Keyword(s):  
Cord Blood ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Intrinsic Factor ◽  
Methionine Synthase ◽  
Vitamin B ◽  
Transcriptional Level ◽  
Gene Variant ◽  
Methionine Synthase Reductase ◽  
Vitamin B 12

ABSTRACT Background The risk of neural tube defects (NTDs) is influenced by nutritional factors and genetic determinants of one-carbon metabolism. A key pathway of this metabolism is the vitamin B-12– and folate-dependent remethylation of homocysteine, which depends on methionine synthase (MS, encoded by MTR), methionine synthase reductase, and methylenetetrahydrofolate reductase. Methionine, the product of this pathway, is the direct precursor of S-adenosylmethionine (SAM), the universal methyl donor needed for epigenetic mechanisms. Objectives This study aimed to evaluate whether the availability of vitamin B-12 and folate and the expression or activity of the target enzymes of the remethylation pathway are involved in NTD risk. Methods We studied folate and vitamin B-12 concentrations and activity, expression, and gene variants of the 3 enzymes in liver from 14 NTD and 16 non-NTD fetuses. We replicated the main findings in cord blood from pregnancies of 41 NTD fetuses compared with 21 fetuses with polymalformations (metabolic and genetic findings) and 375 control pregnancies (genetic findings). Results The tissue concentration of vitamin B-12 (P = 0.003), but not folate, and the activity (P = 0.001), transcriptional level (P = 0.016), and protein expression (P = 0.003) of MS were decreased and the truncated inactive isoforms of MS were increased in NTD livers. SAM was significantly correlated with MS activity and vitamin B-12. A gene variant in exon 1 of GIF (Gastric Intrinsic Factor gene) was associated with a dramatic decrease of liver vitamin B-12 in 2 cases. We confirmed the decreased vitamin B-12 in cord blood from NTD pregnancies. A gene variant of GIF exon 3 was associated with NTD risk. Conclusions The decreased vitamin B-12 in liver and cord blood and decreased expression and activity of MS in liver point out the impaired remethylation pathway as hallmarks associated with NTD risk. We suggest evaluating vitamin B-12 in the nutritional recommendations for prevention of NTD risk beside folate fortification or supplementation.

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