A narrative review on the role of folate-mediated one-carbon metabolism and its associated gene polymorphisms in posing risk to preeclampsia

Mahmood, Sadia; Younas, Hooria; Younus, Amna; Nathenial, Sammar

doi:10.1080/10641963.2021.1916942

Cited by 7 publications

(5 citation statements)

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“…In this study, 1.8% of mid-to-late pregnant women exhibited HHcy, with adequate blood folate and vitamin B 6 identified as protective factors against HHcy. Other studies have similarly indicated that sufficient dietary intake and serum concentrations of folate and other B-vitamins are crucial to maintaining normal Hcy levels ( 38 , 39 ). Moreover, genetic variations in metabolic enzyme-encoding genes could contribute to elevated homocysteine levels ( 38 , 40 , 41 ), though this aspect was not examined in the study.…”

Section: Discussionmentioning

confidence: 94%

“…Insights from the Ottawa and Kingston birth cohort suggest an independent effect of early to mid-pregnancy (38,39). Moreover, genetic variations in metabolic enzyme-encoding genes could contribute to elevated homocysteine levels (38,40,41), though this aspect was not examined in the study. Nevertheless, to mitigate the risk of HHcy and promote maternal-offspring health, attention to folate and other B-vitamin status remains critical.…”

Section: Discussionmentioning

confidence: 95%

“…Clinical studies have highlighted the potential impact of elevated maternal homocysteine during pregnancy on fetal cognitive decline (20) and Down's syndrome (22). Insights from the Ottawa and Kingston birth cohort suggest an independent effect of early to mid-pregnancy (38,39). Moreover, genetic variations in metabolic enzyme-encoding genes could contribute to elevated homocysteine levels (38,40,41), though this aspect was not examined in the study.…”

Section: Discussionmentioning

confidence: 98%

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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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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 98%

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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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“…The most frequent variation of MTRR gene at position 66 causes a substitution of methionine to isoleucine at codon 22 (Elderdery et al., 2022). MTRR rs1801394 (G) allele was known to decrease enzymatic activity leading to higher homocysteine concentration, DNA methylation and thrombotic complications in various diseases (Mahmood et al., 2021). Increased maternal homocysteine levels are associated with various vascular‐related complications of pregnancy (D'Souza & Glazier, 2022).…”

Section: Discussionmentioning

confidence: 99%

The prevalence and linkage disequilibrium of 21 genetic variations related to thrombophilia, folate cycle, and hypertension in reproductive age women of Rostov region (Russia)

Bordaeva,

Derevyanchuk,

Alset

et al. 2023

Annals of Human Genetics

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Several maternal genetic variations are known to play an important role during pregnancy since they can affect mother health and/or fetal growth. The frequency of these variants is variable among different populations. This study aimed to investigate thrombophilia, folate metabolism and hypertension genetic variants in reproductive age women of Rostov region (Russia) and then assess their linkage disequilibrium (LD) and heterogeneity among populations. A total of 3108 reproductive age women were included (33.75 ± 5.13 years). Twenty‐one genetic variants were detected with RT‐PCR. LD was tested according to (D′) coefficient and p value. The highest frequency of mutant allele in studied population was as follows: PAI‐1 rs1799768, MTRR rs1801394, AGT rs699, and AGTR2 rs1403543. We showed a high possibility of coinheritance of MTHFR rs1801133 with rs1801131 and AGT rs699 with rs4762 (D′=0.992 and 0.999, respectively). In addition, comparative analysis showed F7 rs6046, FGB rs1800790, MTR rs1805087, and AGT rs699 significantly more frequent among Rostov females by 1.3–1.5 times than European. MTHFR rs1801133, ADD1 rs4961, AGTR2 rs1403543, NOS3 rs2070744, and rs1799983 were with higher frequencies in Europeans than those in the studied group. Our data could be used as a reference for further associative studies of targeted genetic variations in different pregnancy complications specifically in this population.

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“…Vitamin B12 took part in the re-methylation process of homocysteine to methionine catalyzed by MTR as an intermediate methyl carrier. Suitable intake and serum concentration of folate and vitamin B12 were necessary to maintain the normal concentration of homocysteine ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Interrelation among one-carbon metabolic (OCM) pathway-related indicators and its impact on the occurence of pregnancy-induced hypertension disease in pregnant women supplemented with folate and vitamin B12: Real-world data analysis

Zhang

Lü

et al. 2023

Front. Nutr.

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Background and objectiveA considerable number of pregnant women who were supplemented with folate and vitamin B12 were selected as major participants in studying the one-carbon metabolic (OCM) pathway. Our study aimed to explore the effects of OCM-related indicators on pregnancy-induced hypertension (PIH) and preeclampsia (PE) in pregnant women with folate and vitamin B12 supplementation.Subjects and methodsA total of 1,178 pregnant women who took multivitamin tablets containing 800 μg folate and 4 μg vitamin B12 daily from 3 months before pregnancy to 3 months after pregnancy were enrolled in this study. These pregnant women were classified into three groups: the normotensive group (n = 1,006), the PIH group (n = 131), and the PE group (n = 41). The information on age, weight, body mass index (BMI), number of embryos, gravidity, parity, and OCM-related indicators (serum level of homocysteine, folate, and vitamin B12; MTHFR C677T genotype) was collected.ResultsThe accuracy of the prediction model based on the screened independent risk factors (hyperhomocysteine, OR = 1.170, 95% CI = 1.061–1.291; high folate status, OR = 1.018, 95% CI = 0.999–1.038; and high BMI, OR = 1.216, 95% CI = 1.140–1.297) for PIH in subjects with MTHFR CC genotype (AUC = 0.802) was obviously higher than that in subjects with MTHFR CT, TT genotype (AUC = 0.684,0.685, respectively) by receiver operating characteristic curve analysis. The homocysteine level of the PIH group was significantly higher than that of the normotensive group only in subjects with the MTHFR CC genotype (p = 0.005). A negative correlation between homocysteine and folate appeared in subjects with MTHFR CT + TT genotype (p = 0.005). A model including multiple embryos, nulliparas, and lower folate could predict the process from PIH to PE (AUC = 0.781, p < 0.0001).ConclusionThe prediction model composed of homocysteine, folate, and BMI for PIH was suitable for subjects with MTHFR CC genotype in pregnant women with supplementation of folate and vitamin B12. Lower folate levels could be an independent risk factor in developing the process from PIH to PE.

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A narrative review on the role of folate-mediated one-carbon metabolism and its associated gene polymorphisms in posing risk to preeclampsia

Cited by 7 publications

References 167 publications

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

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

The prevalence and linkage disequilibrium of 21 genetic variations related to thrombophilia, folate cycle, and hypertension in reproductive age women of Rostov region (Russia)

Interrelation among one-carbon metabolic (OCM) pathway-related indicators and its impact on the occurence of pregnancy-induced hypertension disease in pregnant women supplemented with folate and vitamin B12: Real-world data analysis

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