Enciso, M;
Sarasa, J;
Xanthopoulou, L;
Bristow, S;
Bowles, M;
Fragouli, E;
Delhanty, J;
(2016)
Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy.
Human Genetics
, 135
(5)
pp. 555-568.
10.1007/s00439-016-1652-z.
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Enciso et al 2016 Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy AAM.pdf Download (732kB) | Preview |
Abstract
MTHFR is an important enzyme in the metabolism of folic acid and is crucial for reproductive function. Variation in the sequence of MTHFR has been implicated in subfertility, but definitive data are lacking. In the present study, a detailed analysis of two common MTHFR polymorphisms (c.677C>T and c.1298A>C) was performed. Additionally, for the first time, the frequencies of different MTHFR alleles were assessed in preimplantation embryos. Several striking discoveries were made. Firstly, results demonstrated that maternal MTHFR c.1298A>C genotype strongly influences the likelihood of a pregnancy occurring, with the 1298C allele being significantly overrepresented amongst women who have undergone several unsuccessful assisted reproductive treatments. Secondly, parental MTHFR genotypes were shown to affect the production of aneuploid embryos, indicating that MTHFR is one of the few known human genes with the capacity to modulate rates of chromosome abnormality. Thirdly, an unusual deviation from Hardy-Weinberg equilibrium was noted for the c.677C>T polymorphism in subfertile patients, especially those who had experienced recurrent failure of embryo implantation or miscarriage, potentially explained by a rare case of heterozygote disadvantage. Finally, a dramatic impact of the MTHFR 677T allele on the capacity of chromosomally normal embryos to implant is described. Not only do these findings raise a series of interesting biological questions, but they also argue that testing of MTHFR could be of great clinical value, identifying patients at high risk of implantation failure and revealing the most viable embryos during in vitro fertilisation (IVF) cycles.
| Type: | Article |
|---|---|
| Title: | Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00439-016-1652-z |
| Publisher version: | http://dx.doi.org/10.1007/s00439-016-1652-z |
| Language: | English |
| Additional information: | Copyright © Springer-Verlag Berlin Heidelberg 2016. The final publication is available at Springer via http://dx.doi.org/10.1007/s00439-016-1652-z |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Reproductive Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1498716 |
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