Folic acid use in pregnancy and embryo selection

Haggarty, Paul; Campbell, D. M.; Duthie, Susan J.; Andrews, K.; Hoad, Gwen; Piyathilake, Chandrika J.; Fraser, I.D.; McNeill, Geraldine

doi:10.1111/j.1471-0528.2008.01737.x

Cited by 14 publications

(13 citation statements)

References 25 publications

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“…This result cannot be considered as a risk factor because the analysis of the 1298AA and 1298CC genotype frequencies showed similar distribution in children with NTDs and their mothers compared to controls. Similarly, Haggarty et al (2008) reported that the frequency of the 1299CC genotype was essentially the same in the children and their mothers (9.0 and 9.1%, respectively). Furthermore, Cunha et al (2002) could not find a direct association between the A1298C polymorphism and occurrence of NTDs.…”

Section: Discussionmentioning

confidence: 79%

Lack of association between the methylenetetrahydropholate reductase gene A1298C polymorphism and neural tube defects in a Turkish study group

Yildiz¹,

Erdoğan²,

Solak³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The etiology underlying neural tube defects (NTDs) is not fully understood and is believed to involve a complex milieu of genetic and environmental factors. The A1298C polymorphism in the methylenetetrahydropholate reductase gene (MTHFR) has been associated with mild risk for NTDs. In this study, the genotype distribution of the MTHFR gene A1298C polymorphism and the levels of serum homocysteine, vitamin B12, and folate were evaluated in 33 children with NTDs, their mothers, and 46 healthy controls. Genotyping of the A1298C polymorphism was performed by real-time polymerase chain reaction. The A and C allele frequencies in children with NTDs and their mothers were similar to controls (P = 0.160). The 1298AA and 1298CC genotype frequencies (P = 0.551 and 0.062, respectively) in children with NTDs and their mothers did not differ from controls. On the other hand, the 1298AC genotype frequencies in children with NTDs and their mothers were significantly different from controls (P = 0.025). The genotype frequency of 1298AC was lower in children with NTDs than in controls. There was no significant association between clinical distribution of NTDs and 1298AA/AC/CC genotypes (P > 0.05). Serum vitamin B12 levels were higher in children with NTDs than their mothers and controls (P = 0.001). There were no differences among serum homocysteine and folate levels in all groups (P = 0.494 and 0.141, respectively). Both genetic and nutritional factors are important in the etiology of NTDs. Thus, the A1298C polymorphism cannot be regarded as a major risk factor for NTDs.

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Section: Discussionmentioning

confidence: 79%

Lack of association between the methylenetetrahydropholate reductase gene A1298C polymorphism and neural tube defects in a Turkish study group

Yildiz¹,

Erdoğan²,

Solak³

et al. 2016

Genet. Mol. Res.

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“…Furthermore, the selective significance of the T allele was supported by the results of the analysis of the distribution of the frequencies of alleles, genotypes, and haplotypes of the С677Т and А1298С polymorphisms in the MTHFR gene in the Israeli, Japanese, and African populations. According to these data, the 677T allele is found in the haplotypes with a selective advantage [69]. …”

Section: Resultsmentioning

confidence: 99%

The Genetic Diversity and Structure of Linkage Disequilibrium of the MTHFR Gene in Populations of Northern Eurasia

et al. 2012

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The structure of the haplotypes and linkage disequilibrium (LD) of the methylenetetrahydrofolate reductase gene (MTHFR) in 9 population groups from Northern Eurasia and populations of the international HapMap project was investigated in the present study. The data suggest that the architecture of LD in the human genome is largely determined by the evolutionary history of populations; however, the results of phylogenetic and haplotype analyses seems to suggest that in fact there may be a common “old” mechanism for the formation of certain patterns of LD. Variability in the structure of LD and the level of diversity of MTHFRhaplotypes cause a certain set of tagSNPs with an established prognostic significance for each population. In our opinion, the results obtained in the present study are of considerable interest for understanding multiple genetic phenomena: namely, the association of interpopulation differences in the patterns of LD with structures possessing a genetic susceptibility to complex diseases, and the functional significance of the pleiotropicMTHFR gene effect. Summarizing the results of this study, a conclusion can be made that the genetic variability analysis with emphasis on the structure of LD in human populations is a powerful tool that can make a significant contribution to such areas of biomedical science as human evolutionary biology, functional genomics, genetics of complex diseases, and pharmacogenomics.

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“…Haggarty et al report that folic acid intervention has not resulted in genetic selection in favour of the MTHFR 677T allele [27], however this does not take into account potential gene-gene interactions at other folate-related loci and does not discount the possibility that numerous genetic variants may act in concert to exert selective pressure.…”

Section: Discussionmentioning

confidence: 99%

Genetic selection? A study of individual variation in the enzymes of folate metabolism

et al. 2010

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BackgroundGenetic variation in folate metabolism has been associated with survival in utero, the success of in vitro fertilisation, multiple pathologies and longevity.MethodsWe have looked at the prevalence of genetic variants of the enzymes MTHFR and TYMS in 2,898 DNA samples derived from five cohorts collected in the United Kingdom. The simultaneous analysis of genetic variants of the MTHFR and TYMS loci was carried out to investigate a putative gene-gene interaction that was first observed in an elderly male population from Norfolk.ResultsWe have made a consistent observation in five population cohorts; the proportion of individuals who are homozygous for the 2R allele of the 5'UTR TYMS polymorphism is less in individuals who are homozygous for the T allele of MTHFR 677 than in individuals homozygous for the C allele of MTHFR 677 (p = 0.02).ConclusionsThese data may suggest a gene-gene interaction and could be evidence of genetic selection, with some pregnancies more or less viable as a consequence of genetic variation. If these genetic phenomena affect the way folate is handled at the cellular level in utero it is possible that maternal folic acid intake may over-ride such genetic selection.

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Folic acid use in pregnancy and embryo selection

Cited by 14 publications

References 25 publications

Lack of association between the methylenetetrahydropholate reductase gene A1298C polymorphism and neural tube defects in a Turkish study group

Lack of association between the methylenetetrahydropholate reductase gene A1298C polymorphism and neural tube defects in a Turkish study group

The Genetic Diversity and Structure of Linkage Disequilibrium of the MTHFR Gene in Populations of Northern Eurasia

Genetic selection? A study of individual variation in the enzymes of folate metabolism

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