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 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.

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

Methylenetetrahydrofolate reductase gene C677T, A1298C polymorphisms and pre-eclampsia risk: a meta-analysis

2014 ◽  
Vol 41 (8) ◽  
pp. 5435-5448 ◽  
Author(s):  
Xing Li ◽  
Ya L. Luo ◽  
Qiong H. Zhang ◽  
Chen Mao ◽  
Xi W. Wang ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Reductase Gene ◽  
Methylenetetrahydrofolate Reductase Gene
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