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Background <p>One-carbon metabolism links folate and methionine metabolism and this is essential for nucleotide synthesis in the cells. Alterations in one-carbon metabolism are associated with cardiovascular disease (CVD), type 2 diabetes and cancer. Our aim was to investigate whether SNPs in antioxidant-enzyme genes impact the concentrations of folate in serum (s-folate), plasma total homocysteine (p-tHcy) and total glutathione in plasma (p-tGSH) in healthy subjects after supplementation with folic acid.</p> Methods <p>In a randomized, double blind, crossover study, healthy subjects received 0.8&#xa0;mg folic acid per day or a placebo for two weeks. Twenty-four male, and sixty-seven female subjects participated in this study. Participants were aged 36.4 ± 14.8&#xa0;years (mean ± SD). We studied SNPs in six genes by PCR methods. The concentrations of s-folate, p-tHcy and p-tGSH were measured in fasting samples with Cobas and an HPLC-fluorescence method. Student T-tests and ANOVA were used for the statistical calculations.</p> Main findings <p>The subjects with SNP (rs4880) in superoxide dismutase (SOD2) gene (CC) allele had higher concentrations of s-folate and lower concentrations of p-tHcy than subjects with (CT + TT) alleles, (<i>p</i> = 0.014 and <i>p</i> = 0.012). Contrary to SOD2 (CC) allele, the subjects with SNP (rs1001179) catalase (CAT) CC allele had lower concentrations of s-folate (<i>p</i> = 0.029), higher concentrations of p-tGSH (0.017) and higher concentrations of p-tHcy before and after folic acid supplementations (<i>p</i> = 0.015, <i>p</i> = 0.017) than the subjects with (CT + TT) allele. Glutathione transferase (theta)1 (GST-T1) genotype was associated with higher concentrations of s-folate than GST-T0 before (<i>p</i> = 0.025) and after folic acid supplementation (<i>p</i> = 0.047). SNP (rs1050450) in glutathione peroxidase (GPX1) had also impact on the concentrations of p-tGSH (<i>p</i> = 0.011) in healthy subjects.</p> Conclusion <p>SNPs in <i>SOD2 (rs4880), CAT (rs1001179), and GST1</i> impact the concentrations of s-folate, and p-tHcy in healthy subjects before and after folic acid supplementation. Our findings suggest that SNPs in antioxidant-genes have a role in health and disease by impacting the concentrations of s-folate, p-tHcy and p-tGSH.</p>

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Impact of single nucleotide polymorphisms (SNPs) in antioxidant-enzyme genes on the concentrations of folate, homocysteine and glutathione in plasma from healthy subjects after folic acid supplementation – a randomized controlled crossover trial

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  • 发表日期：

    2025年1月21日

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  • Mohammad Azam Mansoor,
  • Tonje Holte Stea,
  • Audun Slettan,
  • Erandie Perera,
  • Ridmi Maddumage,
  • Darshana Kottahachchi,
  • Dhikra Saleem Ali,
  • Rona Cabo,
  • Rune Blomhoff

摘要

Background

One-carbon metabolism links folate and methionine metabolism and this is essential for nucleotide synthesis in the cells. Alterations in one-carbon metabolism are associated with cardiovascular disease (CVD), type 2 diabetes and cancer. Our aim was to investigate whether SNPs in antioxidant-enzyme genes impact the concentrations of folate in serum (s-folate), plasma total homocysteine (p-tHcy) and total glutathione in plasma (p-tGSH) in healthy subjects after supplementation with folic acid.

Methods

In a randomized, double blind, crossover study, healthy subjects received 0.8 mg folic acid per day or a placebo for two weeks. Twenty-four male, and sixty-seven female subjects participated in this study. Participants were aged 36.4 ± 14.8 years (mean ± SD). We studied SNPs in six genes by PCR methods. The concentrations of s-folate, p-tHcy and p-tGSH were measured in fasting samples with Cobas and an HPLC-fluorescence method. Student T-tests and ANOVA were used for the statistical calculations.

Main findings

The subjects with SNP (rs4880) in superoxide dismutase (SOD2) gene (CC) allele had higher concentrations of s-folate and lower concentrations of p-tHcy than subjects with (CT + TT) alleles, (p = 0.014 and p = 0.012). Contrary to SOD2 (CC) allele, the subjects with SNP (rs1001179) catalase (CAT) CC allele had lower concentrations of s-folate (p = 0.029), higher concentrations of p-tGSH (0.017) and higher concentrations of p-tHcy before and after folic acid supplementations (p = 0.015, p = 0.017) than the subjects with (CT + TT) allele. Glutathione transferase (theta)1 (GST-T1) genotype was associated with higher concentrations of s-folate than GST-T0 before (p = 0.025) and after folic acid supplementation (p = 0.047). SNP (rs1050450) in glutathione peroxidase (GPX1) had also impact on the concentrations of p-tGSH (p = 0.011) in healthy subjects.

Conclusion

SNPs in SOD2 (rs4880), CAT (rs1001179), and GST1 impact the concentrations of s-folate, and p-tHcy in healthy subjects before and after folic acid supplementation. Our findings suggest that SNPs in antioxidant-genes have a role in health and disease by impacting the concentrations of s-folate, p-tHcy and p-tGSH.