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

Bucerzan, Simona; Popp, Radu A.; Vlad, Raluca Maria; Lazea, Cecilia; Nicolaescu, Radu; Grigorescu-Sido, Paula

doi:10.1515/rrlm-2017-0003

Cited by 4 publications

(17 citation statements)

References 31 publications

(51 reference statements)

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“…4,5 In 1999, for the first time, studies were published in which it was suggested that polymorphisms within genes coding for enzymes indispensable in folate metabolism might constitute risk factors for chromosomal diseases, including DS. 6 The products of the metabolism of folates are indispensable compounds used in many cellular processes, primarily in the synthesis of nucleic acid precursors and the methylation of cellular components, mainly DNA. The folate cycle also enables the conversion of homocysteine to methionine.…”

Section: Introductionmentioning

confidence: 99%

“…It has been proven that single nucleotide polymorphisms (SNPs) within the MTHFR gene cause a reduction in the activity of this enzyme, resulting in increased levels of homocysteine and in hypomethylation of nucleic acids. 1,[5][6] In vivo studies have demonstrated the influence of epigenetic phenomena, mainly DNA hypomethylation, on the occurrence of instability or incorrect segregation of chromosomes, or of aneuploidy. 7,8 In vitro studies on cell cultures (plant and animal) have confirmed that insufficient DNA methylation may result in chromosomal instability as well as nondisjunction and aberrations.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, researchers have reached the conclusion that folate deficiencies and abnormal expression of the MTHFR gene may pose a risk of chromosomal nondisjunction during meiosis, and, at the same time, increase the risk of trisomy 21 in children. 1,[5][6][7] The polymorphisms of the SNP type within the MTHFR gene most often researched and described are rs1801133 (677CT) and rs1801131 (1298AC). The former is dependent on the transition of cytosine to thymine at position 677 in the 4 th exon of the MTHFR gene.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms of the MTHFR gene in mothers of children with trisomy 21 (Down syndrome) in a Polish population

et al. 2020

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Background. Down syndrome (DS) is the most frequent cause of intellectual disability. In 95% of cases, it is caused by simple trisomy of chromosome 21 resulting from nondisjunction of chromosomes in meiotic division. Currently, the molecular and cellular mechanisms responsible for the phenomenon of nondisjunction are unknown. Objectives. To investigate the incidence of 5 single-nucleotide polymorphisms (SNPs) of the MTHFR gene in a population of Polish mothers who had given birth to children with trisomy 21 in comparison with a control group of women with healthy offspring. Material and methods. The test material comprised venous blood collected from mothers who had given birth to a child with DS (study group, n = 130) as well as from women who had given birth to children without trisomy 21 (control group, n = 88). DNA was isolated using a kit manufactured by Qiagen. Amplification was carried out using a Qiagen Multiplex PCR Kit (Qiagen); genotyping was performed using SNaPshot Genotyping MasterMix (Applied Biosystems). Results. No statistically significant differences were observed in the frequency of genotypes between the examined groups in terms of the polymorphisms of the MTHFR gene. Conclusions. In the Polish population studied, no relationship was found between the occurrence of particular genotypes of the MTHFR gene, i.e., 677CT, 1298AC, rs3737964, rs4846048, and rs1994798, in women and the birth of children with trisomy 21. The results contradict the validity of research on polymorphisms of the MTHFR gene as potential predisposing factors for the occurrence of trisomy 21 in children.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polymorphisms of the MTHFR gene in mothers of children with trisomy 21 (Down syndrome) in a Polish population

et al. 2020

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“…The only documented risk factor for giving birth to a child with trisomy 21 is the mother's age (when > 35 years) [4,5]. In 1999, for the first time, studies were published in which it was suggested that polymorphisms within genes coding for enzymes indispensable in folate metabolism might constitute risk factors for chromosomal diseases, including DS [6].…”

mentioning

confidence: 99%

“…[20], and Croatian (Vraneković et al, 2010)[21] populations. In addition, analogous studies which also excluded the association of DS with the SNP polymorphisms 677CT and 1298AC were carried out in Jordan(Sadiq et al, 2011) [22], Romania(Bucerzan et al, 2017) [6], Brazil (Balarin et al, 2017) [5], Turkey (Boduroglu et al, 2004) [23], China (Jiajin et al, 2018) [1], and India (Kohli et al, 2008; Kaur et al, 2013; Mohanty et al, 2012) [24-26]. Confirmation was also obtained in an extensive metaanalysis by Yang et al (2013), encompassing 32 articles excluding the association of MTHFR polymorphisms of 677CT and 1298AC with trisomy of chromosome 21 [27].…”

mentioning

confidence: 99%

Polymorphisms of the MTHFR Gene in Mothers of Children with Trisomy 21 (Down Syndrome) in a Polish Population

Czechowicz

Małodobra-Mazur

Cukierska

et al. 2019

Preprint

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Background: Down Syndrome (DS) is the most frequent cause of intellectual disability. In 95% of cases, it is caused by simple trisomy of chromosome 21 resulting from nondisjunction of chromosomes in meiotic division. Currently, the molecular and cellular mechanisms responsible for the phenomenon of nondisjunction are unknown. In this paper, we evaluated the incidence of five single-nucleotide polymorphisms (SNPs) of the MTHFR gene in a population of Polish mothers who had given birth to children with trisomy 21 in comparison with a control group of women with healthy offspring. Methods: The test material comprised venous blood collected from mothers who had given birth to a child with Down syndrome (study group, n = 130) as well as from women who had given birth to children without trisomy 21 (control group, n = 88). DNA was isolated using a kit manufactured by Qiagen. Amplification was carried out using a Qiagen Multiplex PCR Kit (Qiagen); genotyping was performed using SNaPshot Genotyping MasterMix (Applied Biosystems). Results: No statistically significant differences were observed in the frequency of genotypes between the examined groups in terms of the polymorphisms of the MTHFR gene. Conclusions: In the studied Polish population, no relationship was found between the occurrence of particular genotypes of the MTHFR gene, i.e. 677CT, 1298AC, rs3737964, rs4846048, and rs1994798, in women and the birth of children with trisomy 21. The results contradict the validity of research on polymorphisms of the MTHFR gene as potential predisposing factors for the occurrence of trisomy 21 in children.

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Maternal MTHFR 677C>T, 1298A>C gene polymorphisms and risk of offspring aneuploidy

et al. 2022

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Objective The objective was to investigate the association between maternal methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, crucial for DNA methylation, and risk of offspring aneuploidy. Methods MTHFR gene polymorphisms 677C>T and 1298A>C were determined by polymerase chain reaction based method, in 163 women with offspring aneuploidy and 155 women with healthy children. Five genetic models were used to assess risk, according to the type of aneuploidy and the age of women at conception. Results MTHFR 677TT genotype and T allele were significantly more prevalent among women with offspring aneuploidy, with an increased risk of aneuploidy demonstrated under a recessive (OR 3.499), homozygote (OR 3.456) and allele contrast model (OR 1.574). The more prominent association was found with sex chromosome aneuploidies and trisomy 13/18, and also in women ≤35 years at conception. No association was observed between 1298A>C polymorphism and risk of offspring aneuploidy, although synergistic effect of two polymorphisms increase the risk of aneuploidy, primarily amplifying the 677T allele effects (p < 0.001). Conclusion Maternal MTHFR 677C>T gene polymorphism, alone or in combination with another 1298A>C polymorphism, appears to be a substantial risk factor for offspring aneuploidy in Montenegro population, especially for sex chromosome aneuploidies and trisomy 13/18, and among younger women.

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

Abstract: 21 (11,8% vs 4,9%; p = 0,033;OR = 2,57

Cited by 4 publications

References 31 publications

Polymorphisms of the MTHFR gene in mothers of children with trisomy 21 (Down syndrome) in a Polish population

Polymorphisms of the MTHFR gene in mothers of children with trisomy 21 (Down syndrome) in a Polish population

Polymorphisms of the MTHFR Gene in Mothers of Children with Trisomy 21 (Down Syndrome) in a Polish Population

Maternal MTHFR 677C>T, 1298A>C gene polymorphisms and risk of offspring aneuploidy

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