Little Evidence of the Protective Role of MTHFR Genetic Polymorfism in Acute Leukaemia and Down Syndrome in Brazil.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4427-4427
Author(s):  
Crisiane W. Zanrosso ◽  
Mariana Emerenciano ◽  
Flavio Ramos ◽  
Alexandre Figueiredo ◽  
Isis Q. Magalhaes ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Methylenetetrahydrofolate Reductase ◽  
Distinct Group ◽  
Mthfr C677t ◽  
Protective Role ◽  
Control Group ◽  
Acute Leukemias ◽  
Reductase Gene ◽  
Pcr Rflp ◽  
Childhood Acute Leukemia

Abstract Immunomolecular and genetic markers are great tools to understand the pathway of leukemogenesis. Because of acute leukemias (ALs) commonly arise as result of DNA damage and/or DNA translocations, the polymorphism of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) have been associated to reduced enzyme activity and altered distribution of cellular folate metabolites. We have determined the prevalence of MTHFR mutations C677T and A1298C in 227 children with AL from different regions of Brazil and 279 region-matched subjects as the control group. PCR-RFLP method was applied using HinfI and MboII restriction digestion to determine the MTHFR 677 and 1298 respectively. Odds ratio (OR) and 95% confidence intervals (95%CI) were used as statistics standard methods. There were 202 acute lymphoblastic leukemias (ALL) and 65 acute myeloid leukemias (AML) from three different regions of Brazil. The frequencies of the 677CC, 677CT and 677TT genotype were 57%, 33%, 10% in the ALL cases; and 51%, 40%, 9% in the controls, respectively. Whereas the frequencies of MTHFR 1298AA, 1298AC and 1298CC were 52%, 40%, 8% in the ALL cases and 61%, 32%, 7% in the controls, respectively. Also, we analyzed separately a group of Down syndrome (DS) cases that include (i) DS with AL and, (ii) DS without AL. The frequencies of the 677CC, 677CT and 677TT genotype were 2,16%, 2,37%, 0% in the DS with AL cases, and 4,31%, 3,02%, 0,22% in the DS without AL, respectively. Whereas the frequencies of MTHFR 1298AA, 1298AC, 1298CC were 2,94%, 1,05%, 0,84% in the DS with AL and 4,83%, 2,10%, 0,63% in the DS without AL, respectively. There were no differences of MTHFR C677T frequencies in both groups in overall analysis. However, the frequency of MTHFR 677 and MTHFR 1298 genotypes differ between cases and controls in different regions of Brazil (p<0.04). The overall analysis indicates that MTHFR C677T and A1298C may confer a protective effect against childhood acute leukemia only in distinct group of cases. Region OD IC (95%) p South 0.41 0.045–3.59 0.69 Southeast 0.78 0.265–2.33 0.84 Northeast 1,02 0.385–2.65 0.69

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.

scholarly journals Functional Inference of Methylenetetrahydrofolate Reductase Gene Polymorphisms on Enzyme Stability as a Potential Risk Factor for Down Syndrome in Croatia

2010 ◽  
Vol 28 (5) ◽  
pp. 293-298 ◽  
Author(s):  
Jadranka Vraneković ◽  
Ivana Babić Božović ◽  
Nada Starčević Čizmarević ◽  
Alena Buretić-Tomljanović ◽  
Smiljana Ristić ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Methylenetetrahydrofolate Reductase ◽  
Enzyme Stability ◽  
Genotype Frequencies ◽  
Reductase Gene ◽  
Pcr Rflp ◽  
Functional Inference ◽  
The Stability ◽  
And Function ◽  
Methylenetetrahydrofolate Reductase Gene

Understanding the biochemical structure and function of the methylenetetrahydrofolate reductase gene (MTHFR) provides new evidence in elucidating the risk of having a child with Down syndrome (DS) in association with two commonMTHFRpolymorphisms, C677T and A1298C. The aim of this study was to evaluate the risk for DS according to the presence ofMTHFRC677T and A1298C polymorphisms as well as the stability of the enzyme configuration. This study included mothers from Croatia with a liveborn DS child (n= 102) or DS pregnancy (n= 9) and mothers with a healthy child (n= 141).MTHFRC677T and A1298C polymorphisms were assessed by PCR-RFLP. Allele/genotype frequencies differences were determined using χ2test. Odds ratio and the 95% confidence intervals were calculated to evaluate the effects of different alleles/genotypes. No statistically significant differences were found between the frequencies of allele/genotype or genotype combinations of theMTHFRC677T and A1298C polymorphisms in the case and the control groups. Additionally, the observed frequencies of the stable (677CC/1298AA, 677CC/1298AC, 677CC/1298CC) and unstable (677CT/1298AA, 677CT/1298AC, 677TT/1298AA) enzyme configurations were not significantly different. We found no evidence to support the possibility thatMTHFRpolymorphisms and the stability of the enzyme configurations were associated with risk of having a child with DS in Croatian population.

scholarly journals MTHFR Gene Polymorphism and Age of Onset of Schizophrenia and Bipolar Disorder

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mohamed A. El-Hadidy ◽  
Hanaa M. Abdeen ◽  
Sherin M. Abd El-Aziz ◽  
Mohammad Al-Harrass
Keyword(s):  
Bipolar Disorder ◽  
Healthy Subjects ◽  
Methylenetetrahydrofolate Reductase ◽  
Age Of Onset ◽  
Age At Onset ◽  
Mthfr C677t ◽  
Control Group ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Mthfr Gene Polymorphism

Objective. Several studies with contradictory results from different cultures about association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in schizophrenia and bipolar disorders. Little is known about this association in Arab culture and Egypt. So the present study aimed to assess the association of MTHFR C677T polymorphism in bipolar disorder (BD) and schizophrenia in comparison to control group. The association between MTHFR C677T polymorphism and the age at onset in schizophrenia or BD was also studied.Methods. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to examine the genotype and allele frequencies of MTHFR C677T polymorphism in 149 healthy subjects and 134 bipolar and 103 schizophrenia patients.Results. In BD and schizophrenia, there was a higher prevalence of MTHFR C677T polymorphism than healthy subjects. Earlier age at onset was found in patients with BD, carrying one copy of the T allele or CT genotypes but not in patients with schizophrenia.Conclusion. The present findings suggest that the MTHFR C677T polymorphisms are likely to be associated with the risk of developing BD and schizophrenia and influence the age at onset of BD but not the age at onset of schizophrenia.

Role of Inherited Thrombophilia Risk Factors in Patients with CKD-5 Receiving Haemodialysis

2020 ◽  
pp. 1-12
Author(s):  
Dimitra Liapi ◽  
Aikaterini Sfiridaki ◽  
Aikaterini Livadiotaki ◽  
Athanasios Alegakis ◽  
Kostas Stylianou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Molecular Mechanisms ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Control Group ◽  
Factor V ◽  
Unknown Aetiology ◽  
Vascular Events ◽  
Thrombophilic Mutations

<b><i>Background:</i></b> The inherited thrombophilic mutations of the factor V gene (FVG1691A Leiden-FVL), prothrombin gene (PTG20210A), and the methylenetetrahydrofolate reductase gene C677T (MTHFR C677T) are risk factors for thromboembolic events and are related to the pathogenesis of vascular diseases. <b><i>Objectives:</i></b> The main objective of this study was to explore the role of these factors in the pathogenesis of chronic kidney disease (CKD) and survival of patients with CKD-5 receiving haemodialysis. <b><i>Methods:</i></b> A cohort of 395 patients with CKD-5 on haemodialysis, from 6 dialysis units in Crete, Greece were recruited based on their medical records and were followed for 5 years. We collected data on CKD-5 aetiology, thrombophilic gene expression, vascular access thrombosis, time of death, and causes of death. <b><i>Results:</i></b> The mutated genes just as prevalent in patients with CKD-5 as they were in a control group with no renal disease (<i>p</i> &#x3e; 0.05). FVL heterozygosity was significantly more prevalent (11.4 vs. 5.7%; <i>p</i> = 0.036) in patients presented with CKD of unknown aetiology, compared to CKD secondary to known aetiologies. The survival of patients with CKD-5 receiving haemodialysis was not affected by the presence of any thrombophilic mutation. This held true for the whole cohort and for the cohort that included only lethal vascular events. Most patients with MTHFR C677T heterozygosity, and all patients with MTHFR C677T homozygosity, died from vascular events during the follow-up period. <b><i>Conclusion:</i></b> The FVL mutation may act as a risk factor for CKD. This study increases our understanding of molecular mechanisms in the pathogenesis of CKD of unknown aetiology. Τhe presence of thrombophilic mutations did not affect the overall survival of patients with CKD-5. This finding probably reflects the effect of medical care on patient outcomes.

scholarly journals The impact of Folate Pathway Polymorphisms Combined to Nutritional Deficiency As a Maternal Predisposition Factor for Down Syndrome

2008 ◽  
Vol 25 (3) ◽  
pp. 149-157 ◽  
Author(s):  
C. B. Santos-Rebouças ◽  
J. C. Corrêa ◽  
A. Bonomo ◽  
N. Fintelman-Rodrigues ◽  
K. C. V. Moura ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Methylenetetrahydrofolate Reductase ◽  
Genetic Profile ◽  
Negative Effects ◽  
Methionine Synthase Reductase ◽  
Genotype Frequencies ◽  
Folate Pathway ◽  
Increased Risk ◽  
Reductase Gene ◽  
The Impact

Polymorphisms in genes encoding folate metabolizing enzymes have been linked to an increased risk of maternal chromosomal nondisjunction in several populations. With the purpose of evaluating this relationship, we compared the frequencies of 677C>T and 1298A>C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and 66A>G in the methionine synthase reductase gene (MTRR) between 103 young mothers of Down syndrome (DS) individuals and 108 control mothers, whose offspring was karyotypically normal, correlating it with an estimative of folate and – related micronutrients levels intake. Maternal and paternal transmission frequencies ofMTHFR677T allele were also examined to access potential parent-of-origin effects. PCR-RFLP for genomic DNA was accomplished and allele/genotype frequencies differences were determined using the x2test, whereas pattern of transmission of theMTHFR677 allele was analyzed by transmission disequilibrium test. None of the polymorphisms seemed to be more frequent in case mothers than in controls, either individually or combined. The estimative of nutritional intake revealed that folate consumption median was inadequate in both groups, whereas methionine and zinc consumption medians were significantly greater in control mothers. It suggests that such interaction between genetic profile and environment could predispose this sub group of women to have a DS child. Additional studies focusing the interaction between nutritional intakes, biochemical data and folate pathway polymorphisms are needed to confirm the present results. The possibility of neutralize the biochemical negative effects of folate-related polymorphisms through oral supplementation could provide new targets for DS prevention.

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.

MTHFR 677CC/1298CC Genotypes Are Highly Associated with Chronic Myelogenous Leukemia: A Case-Control Study in Korea.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4533-4533
Author(s):  
Hee Won Moon ◽  
Tae Young Kim ◽  
Bo Ra Oh ◽  
Hyun Chung Min ◽  
Han Ik Cho ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Protective Role ◽  
Myelogenous Leukemia ◽  
P Value ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Mthfr Polymorphism ◽  
Increased Risk ◽  
Healthy Control

Abstract Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism and DNA methylation. Studies on MTHFR polymorphism in leukemia have largely focused on the protective role of MTHFR polymorphism in ALL. We evaluated the C677T and A1298C polymorphisms using the TaqMan® allelic discrimination assay in various malignancies. The study population included 115 subjects with CML, 200 with AML, 196 with MM and 434 healthy control subjects. The frequency of 1298 CC was statistically significantly higher in subjects with CML than that of the controls (OR = 5.12, 95% CI: 1.75–14.9, P value =.003). Of note, the frequencies of 677CC/1298CC genotype was statistically significantly higher in subjects with CML, AML and MM than that of the controls (OR = 8.8, 3.5, 3.83, P value =.002, 0.036, 0.023, respectively). Our results demonstrate that the MTHFR 1298CC homozygote variant is strongly associated with an increased risk of CML, while MTHFR C677T does not significantly affect the risk of CML. Moreover, we demonstrated that MTHFR 677CC and 1298CC genotype might have combined effect on risk of CML, AML and MM and it is inferred that the A1298C may play a different role in carcinogenesis, depending on the types of organs involved, the types of disease entities and the genotype of C677T.

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