Correlation of methylation status in MTHFR promoter region with recurrent pregnancy loss

Sakai, Mai; Shalabi, Taghreed A.; Amr, Khalda

doi:10.1186/s43141-021-00147-w

“…Nevertheless, the mechanistic effect of DNA methylation in this area of the MTHFR gene expression is not completely clear. Previous studies showed that increased methylation was associated with suppression of gene expression [ 15 ] and disease conditions [ 15 , 70 , 71 ]. On the other hand, recent findings associated a reduction of MTHFR methylation with unfavorable conditions or diseases.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

Bordoni

¹

,

Petracci

²

,

Młodzik-Czyżewska

³

et al. 2022

Oxidative Medicine and Cellular Longevity

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Mitochondrial DNA copy number (mtDNAcn) has been proposed for use as a surrogate biomarker of mitochondrial health, and evidence suggests that mtDNA might be methylated. Intermediates of the one-carbon cycle (1CC), which is duplicated in the cytoplasm and mitochondria, have a major role in modulating the impact of diet on the epigenome. Moreover, epigenetic pathways and the redox system are linked by the metabolism of glutathione (GSH). In a cohort of 101 normal-weight and 97 overweight/obese subjects, we evaluated mtDNAcn and methylation levels in both mitochondrial and nuclear areas to test the association of these marks with body weight, metabolic profile, and availability of 1CC intermediates associated with diet. Body composition was associated with 1CC intermediate availability. Reduced levels of GSH were measured in the overweight/obese group ( p = 1.3 ∗ 10 − 5 ). A high BMI was associated with lower LINE-1 ( p = 0.004 ) and nominally lower methylenetetrahydrofolate reductase (MTHFR) gene methylation ( p = 0.047 ). mtDNAcn was lower in overweight/obese subjects ( p = 0.004 ) and independently correlated with MTHFR methylation levels ( p = 0.005 ) but not to LINE-1 methylation levels ( p = 0.086 ). DNA methylation has been detected in the light strand but not in the heavy strand of the mtDNA. Although mtDNA methylation in the light strand did not differ between overweight/obese and normal-weight subjects, it was nominally correlated with homocysteine levels ( p = 0.035 ) and MTHFR methylation ( p = 0.033 ). This evidence suggests that increased body weight might perturb mitochondrial-nuclear homeostasis affecting the availability of nutrients acting as intermediates of the one-carbon cycle.

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“…Previous studies have reported that imprinted gene defects lead to early pregnancy loss, fetal death, prolonged delivery, and the development of embryo tumors (56)(57)(58)(59). Liang et al found that the maintenance level of the imprinted gene PEGIO is very important for early embryo development, whose down-regulation leads to irreversible pregnancy loss (60). Zhang et al verified that the changes in the expression of imprinted genes and the hypermethylation profile of the repetitive regions (PRE-1 and satellite DNA) in cloned pigs may be related to the developmental defects and early pregnancy loss of the cloned pigs (61).…”

Section: Dna Methylation Of Imprinted Genes and Rplmentioning

confidence: 99%

“…Liang et al. found that the maintenance level of the imprinted gene PEGIO is very important for early embryo development, whose down-regulation leads to irreversible pregnancy loss ( 60 ). Zhang et al.…”

Section: Dna Methylation Of Imprinted Genes and Rplmentioning

confidence: 99%

DNA Methylation and Recurrent Pregnancy Loss: A Mysterious Compass?

Zhou

¹

,

Xiong

²

,

Qu

³

et al. 2021

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Recurrent pregnancy loss (RPL) is a common and severe pathological pregnancy, whose pathogenesis is not fully understood. With the development of epigenetics, the study of DNA methylation, provides a new perspective on the pathogenesis and therapy of RPL. The abnormal DNA methylation of imprinted genes, placenta-specific genes, immune-related genes and sperm DNA may, directly or indirectly, affect embryo implantation, growth and development, leading to the occurrence of RPL. In addition, the unique immune tolerogenic microenvironment formed at the maternal-fetal interface has an irreplaceable effect on the maintenance of pregnancy. In view of these, changes in the cellular components of the maternal-fetal immune microenvironment and the regulation of DNA methylation have attracted a lot of research interest. This review summarizes the research progress of DNA methylation involved in the occurrence of RPL and the regulation of the maternal-fetal immune microenvironment. The review provides insights into the personalized diagnosis and treatment of RPL.

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“…One of the primary BDP features is the presence of a susceptible CpG Island (CGI) to DNA methylation (12). The promoters' methylation is associated with various diseases, and the level of CGI methylation is a further factor in the severity of the disease (12)(13)(14). In the current study, peripheral blood from FD patients from the same family carrying a GLA deletion mutation was used to investigate the possible accumulative effects of GLA deletion mutation with BDP methylation levels on the severity of the disease in FD patients and on the GLA and HNRNPH2 expression.…”

Section: Introductionmentioning

confidence: 99%

The potential consequences of bidirectional promoter methylation on GLA and HNRNPH2 expression in Fabry disease phenotypes in a family of patients carrying a GLA deletion variant

Al‐Obaide

¹

,

Al-Obaidi

²

,

Vasylyeva

³

2022

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Fabry disease (FD) is a rare inherited disease characterized by a wide range of symptoms attributed to GLA mutations resulting in defective α-galactosidase A (α-Gal A) and accumulation of glycosphingolipids. The GLA locus is paired in a divergent manner with the heterogeneous nuclear ribonucleoprotein HNRNPH2 locus mapped in the RPL36A-HNRNPH2 readthrough locus. As a follow-up to our recent finding of the co-regulation of GLA and HNRNPH2 via a bidirectional promoter (BDP) in normal kidney and skin cells, the potential accumulative influence of BDP methylation and GLA mutation on the severity of FD in patients from the same family, two males and two females carrying a GLA deletion mutation, c.1033_1034delTC (p.Ser345Argfs) was addressed in the present study. The molecular analyses of the FD patients compared with the control revealed that the expression of GLA was significantly low (P<0.05), and HNRNPH2 showed a tendency of low expression (P=0.1) when BDP methylation was elevated in FD patients, compared with low BDP methylation and high GLA expression (P<0.05), and a high trend of HNRNPH2 expression in normal individuals. The accumulative effects of the mutation and BDP methylation with the severity of the disease were observed in three patients. One male FD patient, a member of the FD family diagnosed with progressive loss of kidney function, hypertension, and eventually a stroke, and the lowest level of α-Gal A enzyme activity showed the highest BDP DNA methylation level. It is concluded that the DNA methylation of GLA-HNRNPH2 BDP may serve a role in diagnosing and treating FD.

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Correlation of methylation status in MTHFR promoter region with recurrent pregnancy loss

Cited by 10 publications

References 33 publications

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

DNA Methylation and Recurrent Pregnancy Loss: A Mysterious Compass?

The potential consequences of bidirectional promoter methylation on GLA and HNRNPH2 expression in Fabry disease phenotypes in a family of patients carrying a GLA deletion variant

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