The Effect of Multiple Single Nucleotide Polymorphisms in the Folic Acid Pathway Genes on Homocysteine Metabolism

Liang, Shuang; Zhou, Yuanpeng; Wang, Huijun; Qian, Yanyan; Ma, Duan; Tian, Weidong; Persaud-Sharma, Vishwani; Chen, Yu; Ren, Yanling; Zhou, Shu-Feng; Li, Xiaotian

doi:10.1155/2014/560183

Cited by 28 publications

(16 citation statements)

References 29 publications

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“…Folate is the basic acceptor molecule for one‐carbon metabolism, and as a result, the finding that patients with NSCLP (and their mothers) showed lower serum folic acid concentrations than the controls reinforces the previously delineated association between folate metabolism and the pathogenesis of orofacial clefts (Platek et al , ; Bhaskar et al , ; Liang et al , ). Reduced levels of folate can cause reduction in SAM levels, leading to impairment and likely insufficiency in DNA methylation, which an epigenetic mechanism that regulates genomic programming during embryogenesis (de Arruda et al , ).…”

Section: Discussionsupporting

confidence: 78%

Genetic and non‐genetic factors that increase the risk of non‐syndromic cleft lip and/or palate development

et al. 2014

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Section: Discussionsupporting

confidence: 78%

Genetic and non‐genetic factors that increase the risk of non‐syndromic cleft lip and/or palate development

et al. 2014

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“…18 CBS rs2851391 was associated with a change in postmethionine load Hcy levels 19 and plasma Hcy levels of subjects with rs2851391 TT genotype were significantly higher compared to that of the TC and CC genotypes. 20 The presence of CBS rs706209 may affect pre-mRNA splicing, which could generate an aberrant CBS protein and consequently affect Hcy metabolism. 11,21 The methylation levels of patients with a mutant heterozygote and homozygote of the two SNPs were higher than those with a wild homozygote.…”

Section: Discussionmentioning

confidence: 99%

CBS gene polymorphism and promoter methylation‐mediating effects on the efficacy of folate therapy in patients with hyperhomocysteinemia

Zhao

Zhang

et al. 2020

The Journal of Gene Medicine

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Background A decrease in cystathionine beta‐synthase (CBS) enzyme activity could lead to hyperhomocysteinemia (HHcy). Studies have revealed that DNA methylation has a mediating effect on the development of diseases. The present study aimed to explore CBS promoter methylation‐mediating effects on the efficacy of folate treatment for HHcy. Methods HHcy patients were treated with folate (5 mg/day) for 90 days and then divided into a failure group (Hcy ≥ 15 μmol/l) and a success group (Hcy < 15 μmol/l) according to post‐treatment plasma Hcy levels. Genotyping of CBS gene (rs2851391 and rs706209) in patients (n = 638) was detected using a MassArray system (Sequenom, San Diego, CA, USA). The baseline DNA methylation levels of patients (n = 299) were detected using MethylTarget™ technology (Genesky Biotechnologies Inc., Shanghai, China). Results The CBS rs2851391 TC + CC genotype was related to a 57% reduction of failure risk in HHcy treatment compared to the TT genotype (95% confidence interval [CI] = 0.19–0.97). The CBS rs706209 CT + TT genotype had a 2.97‐fold increased risk of failure to treatment compared to the CC genotype (95% CI = 1.52–5.80). After adjustment for confounding factors, the odds ratio (95% CI) for the risk of failure in HHcy treatment in total and male patients was 0.55 (0.32–0.93) and 0.34 (0.16–0.69), respectively, for patients with higher methylation levels (≥ methylation median). Additionally, baseline CBS promoter methylation mediated 33.39% of the effect of rs2851391 on the efficacy of folate treatment for HHcy (ACME [average causal mediation effects]: –0.05, 95% CI = –0.11 to 0.00, p = 0.046). Conclusions The present study indicates that CBS gene polymorphism and promoter methylation could affect the efficacy of HHcy. There were potentially causal effects of genetic, epigenetic variations at the CBS rs2851391 locus on the efficacy of HHcy therapy with folate.

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“…4, 21 Moreover, the MTHFR gene has been extensively studied due to the observation that carriers of the C677T variant have reduced enzyme function, resulting in both increased levels of Hcy and an increased risk of depression. 89, 90 Therefore, it is hypothesized (Fig. 2) that supplemental FA is inhibiting MTHFR by DHF, thus impairing folate metabolism further in people with the MTHFR C677T mutation and resulting in a functional deficiency of folate.…”

Section: Future Research Directionsmentioning

confidence: 99%

Effect of Folate Supplementation on Inflammatory Markers in Individuals Susceptible to Depression: A Systematic Review

Barnett¹,

D’Cunha

Georgousopoulou

et al. 2017

Exploratory Research and Hypothesis in Medicine

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Folate has been proposed to be an efficacious treatment strategy for depression. The mandatory fortification of flour with synthetic folic acid (FA) in over 80 countries has yielded improvements in folate intake; however, depression is still a considerable public health concern. While there are established benefits of FA fortification in reducing risk of neural tube defects, the implications regarding depression are unclear, especially in individuals with certain genetic polymorphisms. Therefore, a systematic review was conducted to examine the effects of folate to treat depression. Following PRISMA guidelines, a systematic review was conducted of electronic databases (PUBMED, Scopus, CINAHL, and Cochrane Library) to identify human clinical trials examining the effects of folate (including FA) supplementation in the management or prevention of depression, the impact on inflammatory markers and if genetic polymorphisms were considered. Ten trials met the inclusion criteria. Seven trials examined effects of either adjunctive FA or L-methylfolate (L-MTHF) supplementation with antidepressants in the management of depression and three examined effects of FA supplementation alone for prevention of depression. No benefit of FA was found compared to placebo (all, p > 0.05). The single L-MTHF trial that explored the interplay of genetic polymorphisms and methylation status found benefit in the Hamilton depression rating scale from adjunctive treatment with 15 mg/day of L-MTHF compared with placebo (−6.8 ± 7.2 vs. −3.7 ± 6.5; p = 0.017) and improvement with L-MTHF for most genetic markers. Currently, there is no evidence to support FA supplementation for the management or prevention of depression. More research is required to determine the efficacy of L-MTHF and folinic acid in certain clinical populations.

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The Effect of Multiple Single Nucleotide Polymorphisms in the Folic Acid Pathway Genes on Homocysteine Metabolism

Cited by 28 publications

References 29 publications

Genetic and non‐genetic factors that increase the risk of non‐syndromic cleft lip and/or palate development

Genetic and non‐genetic factors that increase the risk of non‐syndromic cleft lip and/or palate development

CBS gene polymorphism and promoter methylation‐mediating effects on the efficacy of folate therapy in patients with hyperhomocysteinemia

Effect of Folate Supplementation on Inflammatory Markers in Individuals Susceptible to Depression: A Systematic Review

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