Genetic Variation of Methylenetetrahydrofolate Reductase (MTHFR) and Thymidylate Synthase (TS) Genes Is Associated with Idiopathic Recurrent Implantation Failure

Choi, Youngsok; Kim, Jung Oh; Shim, Sung Han; Lee, Yubin; Kim, Ji Hyang; Jeon, Young Joo; Ko, Jung Jae; Lee, Woo Sik; Kim, Nam Keun

doi:10.1371/journal.pone.0160884

Cited by 22 publications

(19 citation statements)

References 33 publications

(28 reference statements)

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“…We cannot exclude that inheritance of such a genotype by an embryo could be lethal in very early embryo development. This observation has been reported in several studies [ 18 , 34 ].…”

Section: Discussionsupporting

confidence: 89%

“…Whereas MTHFR polymorphisms have been widely investigated in RSA case-control and meta-analysis studies [ 15 – 17 ], the association of RIF with MTHFR polymorphisms has been evaluated in only a few studies [ 7 , 18 – 20 ]. The results and conclusions were contradictory, even between meta-analysis studies [ 8 , 15 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population

et al. 2017

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Almost 1600 individuals from the Polish population were recruited to this study. Among them 319 were fertile couples, 289 were recurrent spontaneous abortion (RSA) couples, and 131 were in the group of recurrent implantation failure (RIF) following in vitro fertilization. The aim of this study was to evaluate the MTHFR c.c.677 C>T and c.c.1298 A>C polymorphisms’ association with RSA and RIF. We used PCR-RFLP with HinfI (677 C>T) and MboII (1298 A>C) digestion. We observed a protective effect of the female AC genotype (OR = 0.64, p = 0.01) and the C allele (AC+CC genotypes; OR = 0.65, p = 0.009) against RSA. Moreover, 1298 AA/677 CT women were more frequent in RSA (31.14%) and RIF (25.20%) groups in comparison to fertile women (22.88%), although this difference was significant only in the case of RSA (p = 0.022, OR = 1.52). Male combined genotype analysis revealed no association with reproductive failure of their partners. Nevertheless, the female/male combination AA/AC of the 1298 polymorphism was more frequent in RSA couples (p = 0.049, OR = 1.49). However, the significant results became insignificant after Bonferroni correction. In addition, analysis of haplotypes showed significantly higher frequency of the C/C haplotype (1298 C/677 C) in the female control group than in the female RSA group (p = 0.03, OR = 0.77). Moreover, the association between elevated homocysteine (Hcy) level in plasma of RSA and RIF women and MTHFR polymorphisms was investigated but did not reveal significant differences. In conclusion, for clinical practice, it is better to check the homocysteine level in plasma and, if the Hcy level is increased, to recommend patients to take folic acid supplements rather than undergo screening of MTHFR for 1298 A>C and 677 C>T polymorphisms.

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“…We cannot exclude that inheritance of such a genotype by an embryo could be lethal in very early embryo development. This observation has been reported in several studies [ 18 , 34 ].…”

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population

et al. 2017

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“…However, in the majority of cases, the cause of RIF remains unknown. 1,6,7 MicroRNAs (miRNAs) are a class of small (approximately 18*22 nucleotide) noncoding RNAs that are critical for the regulation of gene expression. These RNA species mediate posttranscriptional gene expression by binding to the 3 0 -untranslated regions (UTRs), of target mRNAs in a sequence dependent manner, leading to transcript degradation and translational repression.…”

Section: Introductionmentioning

confidence: 99%

“…However, in the majority of cases, the cause of RIF remains unknown. 1,6,7…”

Section: Introductionmentioning

confidence: 99%

Association Between miR-605 A>G, miR-608 G>C, miR-631 I>D, miR-938 C>T, and miR-1302-3 C>T Polymorphisms and Risk of Recurrent Implantation Failure

et al. 2019

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Recurrent implantation failure (RIF) is diagnosed when pregnancy failure occurs after 2 consecutive in vitro fertilization-embryo transfers (IVF-ET) to the endometrium using at least 4 high-quality embryos. MicroRNAs (miRNAs) are a class of small noncoding RNA and reported to play an important role in cell proliferation as well as implantation process. Recently, it has been reported that miRNA can regulate RIF occurrence. So, we were to examine the association between the specific miRNA polymorphisms and RIF in Korean women. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to determine the frequency of the following polymorphisms: miR-605A>G, miR-608G>C, miR-631I>D, miR-938C>T, and miR-1302-3C>T. Our results demonstrate a decreased incidence of RIF in patients with the miR-1302-3C>T polymorphism (adjusted odds ratio [AOR], 0.234; 95% confidence interval [CI], 0.089-0.618; P = .003). Based on our allele combination analysis, the C-T ( miR-938/ miR-1302-3: OR = 0.259; 95% CI, 0.100-0.674; P = .003) allele was also associated with decreased RIF risk. From our interaction analysis with miR-1302-3, the miR-1302-3CC genotype (AOR = 43.332; 95% CI, 5.576-336.745) showed an association with RIF prevalence in participants with an activated partial thromboplastin time (aPTT) ≤22.6. We found that the miR-1302-3C>T polymorphism is significantly associated with RIF development in Korean women. Specifically, our study suggests that the T allele of miR-1302-3 may decrease the risk of RIF in Korean women.

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“…including tumor protein P53, cyclooxygenase-2 (COX-2), methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), nuclear factor kappa B (NF-κB), plasminogen activator inhibitor-1, vascular endothelial growth factor, and leukocyte antigen-G [3][4][5][6][7][8][9]. Among these candidate RIFsusceptibility genes, the human leucocyte antigen-G (HLA-G) gene was one of the most extensively explored.…”

Section: Introductionmentioning

confidence: 99%

The HLA-G 14-bp polymorphism and recurrent implantation failure: a meta-analysis

Fan¹,

Huang²,

Li³

et al. 2017

J Assist Reprod Genet

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Genetic Variation of Methylenetetrahydrofolate Reductase (MTHFR) and Thymidylate Synthase (TS) Genes Is Associated with Idiopathic Recurrent Implantation Failure

Cited by 22 publications

References 33 publications

The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population

The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population

Association Between miR-605 A>G, miR-608 G>C, miR-631 I>D, miR-938 C>T, and miR-1302-3 C>T Polymorphisms and Risk of Recurrent Implantation Failure

The HLA-G 14-bp polymorphism and recurrent implantation failure: a meta-analysis

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