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Background <p>Gestational diabetes mellitus (GDM) is a significant pregnancy complication, and its relationship with serum levels of B vitamins and homocysteine (Hcy) remains unclear. This study&#xa0;aims to investigate the causal associations between genetically predicted serum levels of B vitamins (vitamin B6, B12, and folate) and Hcy with GDM risk.</p> Methods <p>Independent single nucleotide polymorphisms (SNPs) associated with Hcy (<i>n</i> = 14), Hcy (independent of BMI) (<i>n</i> = 11), vitamin B6 (<i>n</i> = 16), vitamin B12 (<i>n</i> = 8), folate (<i>n</i> = 14), and folate (independent of BMI) (<i>n</i> = 13) were selected as instrumental variables (IVs) based on genome-wide significance. Summary-level data for GDM were sourced from the FinnGen consortium.</p> Results <p>The MR analysis demonstrated a significant association between serum Hcy levels and GDM risk [OR (95% CI) = 1.28 (1.09, 1.51), <i>p</i> = 0.003] using the inverse variance weighting (IVW) method. Following the exclusion of BMI-related IVs, a suggestive association was observed between serum Hcy levels and GDM risk [OR (95% CI) = 1.26 (1.04, 1.54), <i>p</i> = 0.019].</p> Conclusions <p>Our study indicates a suggestive association between Hcy levels and GDM, emphasizing the necessity for additional research to explore the role of Hcy in GDM management.</p>

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Investigating the role of homocysteine and B vitamins in gestational diabetes mellitus: Mendelian randomization study

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  • 发表日期：

    2025年10月31日

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  • Xiaojing Zhan,
  • Huilian Chen,
  • Yifei Lin,
  • Yiming Hu

摘要

Background

Gestational diabetes mellitus (GDM) is a significant pregnancy complication, and its relationship with serum levels of B vitamins and homocysteine (Hcy) remains unclear. This study aims to investigate the causal associations between genetically predicted serum levels of B vitamins (vitamin B6, B12, and folate) and Hcy with GDM risk.

Methods

Independent single nucleotide polymorphisms (SNPs) associated with Hcy (n = 14), Hcy (independent of BMI) (n = 11), vitamin B6 (n = 16), vitamin B12 (n = 8), folate (n = 14), and folate (independent of BMI) (n = 13) were selected as instrumental variables (IVs) based on genome-wide significance. Summary-level data for GDM were sourced from the FinnGen consortium.

Results

The MR analysis demonstrated a significant association between serum Hcy levels and GDM risk [OR (95% CI) = 1.28 (1.09, 1.51), p = 0.003] using the inverse variance weighting (IVW) method. Following the exclusion of BMI-related IVs, a suggestive association was observed between serum Hcy levels and GDM risk [OR (95% CI) = 1.26 (1.04, 1.54), p = 0.019].

Conclusions

Our study indicates a suggestive association between Hcy levels and GDM, emphasizing the necessity for additional research to explore the role of Hcy in GDM management.