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      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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          Abstract

          Background and objective

          A 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 methods

          A 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.

          Results

          The 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).

          Conclusion

          The 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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          Most cited references35

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          Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks.

          The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism and protein, DNA, and RNA synthesis. The enzyme is responsible for maintaining methionine and homocysteine (Hcy) balance to prevent cellular dysfunction. Polymorphisms in the MTHFR gene, especially C677T, have been associated with various diseases, including cardiovascular diseases (CVDs), cancer, inflammatory conditions, diabetes, and vascular disorders. The C677T MTHFR polymorphism is thought to be the most common cause of elevated Hcy levels, which is considered an independent risk factor for CVD. This polymorphism results in an amino acid change from alanine to valine, which prevents optimal functioning of the enzyme at temperatures above 37 °C. Many studies have been conducted to determine whether there is an association between the C677T polymorphism and increased risk for CVD. There is much evidence in favour of this association, while several studies have concluded that the polymorphism cannot be used to predict CVD development or progression. This review discusses current research regarding the C677T polymorphism and its relationship with CVD, inflammation, diabetes, and epigenetic regulation and compares the evidence provided for and against the association with CVD.
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            Hypertension During Pregnancy.

            Hypertensive disorders of pregnancy affect about 5-10% of pregnancies impacting maternal, fetal, and neonatal outcomes. We review the recent studies in this field and discuss the pathophysiology, diagnosis, and management of hypertension during pregnancy, as well as the short- and long-term consequences on the cardiovascular health of women.
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              Associations of MTHFR Gene Polymorphisms with Hypertension and Hypertension in Pregnancy: A Meta-Analysis from 114 Studies with 15411 Cases and 21970 Controls

              Background Several epidemiological studies have investigated the associations of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with hypertension (H) or hypertension in pregnancy (HIP). However, the results were controversial. We therefore performed a comprehensive meta-analysis to provide empirical evidences on the associations. Methodologies The English and Chinese databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Meta-regression, subgroup analysis, sensitivity analysis, cumulative meta-analysis and assessment of publication bias were performed in our study. Principal Findings A total of 114 studies with 15411 cases and 21970 controls were included, 111 studies with 15094 cases and 21633 controls for the C677T polymorphism and 21 with 2533 cases and 2976 controls for the A1298C polymorphism. Overall, the C677T polymorphism was significantly associated with H and HIP (H & HIP: OR = 1.26, 95% CI = 1.17–1.34; H: OR = 1.36, 95% CI = 1.20–1.53; HIP: OR = 1.21, 95% CI = 1.08–1.32). Stratified analysis by ethnicity revealed a significant association among East Asians and Caucasians, but not among Latinos, Black Africans, and Indians and Sri Lankans. In the stratified analyses according to source of controls, genotyping method, sample size and study quality, significant associations were observed in all the subgroups, with the exception of population based subgroup in H studies and large sample size and “others” genotyping method subgroups in HIP studies. For the A1298C polymorphism, no significant association was observed either in overall or subgroup analysis under all genetic models. Conclusions This meta-analysis suggests that the MTHFR C677T rather than A1298C polymorphism may be associated with H & HIP, especially among East Asians and Caucasians.
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                Author and article information

                Contributors
                Journal
                Front Nutr
                Front Nutr
                Front. Nutr.
                Frontiers in Nutrition
                Frontiers Media S.A.
                2296-861X
                10 January 2023
                2022
                : 9
                : 950014
                Affiliations
                [1] 1Department of Pharmacy, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China
                [2] 2Shanghai Key Laboratory of Embryo Original Diseases , Shanghai, China
                [3] 3Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China
                [4] 4Division of Maternal-Fetal Fetal Medicine, Prenatal Diagnosis Center, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China
                Author notes

                Edited by: Debora Leite, Federal University of Pernambuco, Brazil

                Reviewed by: Sreedhar Ranganath Pai, Manipal Academy of Higher Education, India; Chun Yang, Chinese Center For Disease Control and Prevention, China; Simmi Kharb, Pandit Bhagwat Dayal Sharma University of Health Sciences, India

                *Correspondence: Junwei Fan, drjunweifan@ 123456163.com

                These authors have contributed equally to this work

                This article was submitted to Clinical Nutrition, a section of the journal Frontiers in Nutrition

                Article
                10.3389/fnut.2022.950014
                9871780
                36704788
                7295152e-2603-4095-92a3-c5e5c5e49375
                Copyright © 2023 Zhang, Gu, Lei, Wang, Sun, Fan, Wang and Zhang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 24 May 2022
                : 19 December 2022
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 35, Pages: 13, Words: 7878
                Categories
                Nutrition
                Original Research

                one-carbon metabolism,folate,vitamin b12,homocysteine,methylenetet-rahydrofolate reductase,pregnancy-induced hypertension

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