Gene specific epigenetic regulation of hepatic folate transport system is responsible for perturbed cellular folate status during aging and exogenous modulation

Najar, Rauf Ahmad; Rahat, Beenish; Hussain, Aashiq; Thakur, Shilpa; Kaur, Jaspreet; Kaur, Jyotdeep; Hamid, Abid

doi:10.1002/mnfr.201500991

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…Low levels of dietary folate cause aberrant DNA methylation pattern and can lead to perturbed biosynthesis [10, 41]. Therefore, we determined the methylation profile of the Esr1 , Cav1 , and Elavl1 promoter regions in the human sperm DNA.…”

Section: Discussionmentioning

confidence: 99%

Effect of folate deficiency on promoter methylation and gene expression ofEsr1, Cav1, andElavl1, and its influence on spermatogenesis

et al. 2017

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This study aims to investigate the effect of folate deficiency on the male reproductive function and the underlying mechanism. A total of 269 screened participants from 421 recruitments were enrolled in this study. An animal model of folate deficiency was constructed. Folate concentration was measured in the ejaculate, and its association with semen parameters was then determined. The expression and promoter methylation status of ESR1, CAV1, and ELAVL1 were also evaluated. Results showed that seminal plasma folate level was significantly lower among subjects with azoospermia than those with normozoospermia. Low folate level was significantly correlated with low sperm concentration in men with normozoospermia. Folate deficiency significantly reduced the expression of ESR1, CAV1, and ELAVL1, which are critical to spermatogenesis. However, low folate levels did not increase the methylation levels of the promoter regions of ESR1, CAV1, and ELAVL1 in human sperm DNA. Thus, folate deficiency impairs spermatogenesis may partly due to inhibiting the expression of these genes. Thus future research should determine the significance of sufficient folate status in male fertilization and subsequent pregnancy outcomes.

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Section: Discussionmentioning

confidence: 99%

Effect of folate deficiency on promoter methylation and gene expression ofEsr1, Cav1, andElavl1, and its influence on spermatogenesis

et al. 2017

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“…However, the specific mechanism was still unclear. Specially, lack of folic acid led to demethylation of ABCG2 (Ahmad Najar et al, 2016), lack of Vitamin D led to hypermethylation of CYP24A1 and CYP27B1 (Anderson et al, 2015; Wang et al, 2020). The folic acid excretion cells increased or decreased when folic acid was excessive or deficient.…”

Section: Resultsmentioning

confidence: 99%

“…This process was transported by ABCG2 and the expression of ABCG2 was regulated by methylation. Finally, the total folic acid maintained stable (Ahmad Najar et al, 2016). 24-Hydroxylase encoded by the CYP24A1 gene was a catabolic enzyme and both 25(OH)D and 125(OH)2D were catabolized by the 24-hydroxylase into inactive metabolites, thereby lowering the vitamin D levels (Wang et al, 2020).…”

Section: Obesity and Dietmentioning

confidence: 99%

Impact of individual factors on DNA methylation of drug metabolism genes: A systematic review

Bian

Zhao

et al. 2023

Environ and Mol Mutagen

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Individual differences in drug response have always existed in clinical treatment. Many non‐genetic factors show non‐negligible impacts on personalized medicine. Emerging studies have demonstrated epigenetic could connect non‐genetic factors and individual treatment differences. We used systematic retrieval methods and reviewed studies that showed individual factors' impact on DNA methylation of drug metabolism genes. In total, 68 studies were included, and half(n = 36) were cohort studies. Six aspects of individual factors were summarized from the perspective of personalized medicine: parental exposure, environmental pollutants exposure, obesity and diet, drugs, gender and others. The most research (n = 11) focused on ABCG1 methylation. The majority of studies showed non‐genetic factors could result in a significant DNA methylation alteration in drug metabolism genes, which subsequently affects the pharmacokinetic processes. However, the underlying mechanism remained unknown. Finally, some viewpoints were presented for future research.This article is protected by copyright. All rights reserved.

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“…Additionally, women belonging to lower educational level and SES often have infrequent antenatal visits, which diminishes their opportunities for dietary assessments, necessary adjustments, and adequate supplementation ( 32 , 33 ). While some studies suggest that older women are more likely to adhere to healthier diets ( 32 ), animal research indicated that folate-modulated DNA methylation decreased with age ( 34 , 35 ). This could explain the notably lower serum methionine levels observed in pregnant women aged 35 and above in this study.…”

Section: Discussionmentioning

confidence: 99%

Assessment of blood one-carbon metabolism indexes during mid-to-late pregnancy in 397 Chinese pregnant women

Zhang,

Wu,

et al. 2024

Front. Nutr.

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ObjectivesOne-carbon metabolism (OCM) significantly influences fetal growth and neurodevelopment through transferring methyl group to biomolecules, during which folate, methionine, choline and betaine function as methyl donor nutrients, while vitamin B2, B6, B12 function as enzyme cofactors, and homocysteine (Hcy) and S-adenosyl methionine (SAM) are functional metabolites. This study aimed to assess blood OCM index levels and explore their relationships among Chinese pregnant women.MethodsData were obtained from the baseline of the Mother–Child Nutrition and Health Cohort Study. Pregnant women, voluntarily recruited from September 2020 to June 2022 during antenatal examinations in five Chinese cities at 24–32 gestational weeks, provided fasting venous blood samples. Measurements included RBC and serum folate, serum vitamin B2, B6, B12, choline, betaine, methionine, total Hcy (tHcy), and plasma SAM. Sociodemographic characteristics and pregnancy-related conditions were collected via a self-designed questionnaire.ResultsOf 397 participants, 82.6% were in mid-pregnancy (24–27 gestational weeks) and 17.4% were in late-pregnancy (28–32 gestational weeks). Serum folate, vitamin B6, and B12 deficiencies were 2.5, 1.3, and 8.3%, respectively. Elevated tHcy (≥10 μmol/L) was observed in 1.8% of pregnant women. Elderly pregnant women (aged 35 and above) exhibited significantly lower serum methionine levels (p < 0.05), while multiparous women had lower RBC folate levels (p < 0.05), and lower serum methionine and vitamin B12 levels (p < 0.10, not statistically significant). Partial correlation analysis revealed positive associations between RBC folate and cofactor vitamin B12 (r = 0.244, p < 0.05) in the folate cycle, as well as significant correlations between two methyl donor paths [serum folate was significantly related to serum choline (r = 0.172) and betaine (r = 0.193)]. As functional biomarkers of OCM, serum tHcy exhibited negative associations with RBC folate (β = −0.330, p < 0.05) and vitamin B6 (β = −0.317, p < 0.05), and plasma SAM displayed a positive association with serum betaine (β = 0.610, p < 0.05), while negatively associated with serum vitamin B6 (β = −0.181, p < 0.05).ConclusionThe blood OCM exhibited imbalances during mid-to-late pregnancy, characterized by lower levels of folate, vitamin B6, and B12, alongside elevated tHcy levels. Adequate folate and vitamin B6 emerged as significant predictors of lower tHcy levels. Additionally, serum betaine showed a positive correlation with plasma SAM. This suggests the importance of not only ensuring sufficient folate but also optimizing other OCM-related nutrients throughout pregnancy.

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Gene specific epigenetic regulation of hepatic folate transport system is responsible for perturbed cellular folate status during aging and exogenous modulation

Abstract: Promoter hypermethylation of RFC and promoter hypomethylation of ABCG2 may be attributed to the down regulation of RFC and up regulation of ABCG2 at mRNA and protein levels in conditions of 3 and 5 months of folate deficiency in the adult group.

Cited by 7 publications

References 38 publications

Effect of folate deficiency on promoter methylation and gene expression ofEsr1, Cav1, andElavl1, and its influence on spermatogenesis

Effect of folate deficiency on promoter methylation and gene expression ofEsr1, Cav1, andElavl1, and its influence on spermatogenesis

Impact of individual factors on DNA methylation of drug metabolism genes: A systematic review

Assessment of blood one-carbon metabolism indexes during mid-to-late pregnancy in 397 Chinese pregnant women

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