Increasing prevalence of gestational diabetes mellitus when carrying the T variant allele of the MTHFR gene C677T polymorphism: a systematic review and meta-analysis

Arch Gynecol Obstet. 2022 May;305(5):1193-1202. doi: 10.1007/s00404-021-06303-4. Epub 2021 Oct 25.

Abstract

Purpose: Previous epidemiological data linking the C677T and A1298C MTHFR polymorphisms to gestational diabetes risk have been mixed and controversial. Therefore, we conducted this meta-analysis to derive a more precise estimation of the relationship between MTHFR polymorphisms and this pregnancy disorder.

Methods: A systematic literature search for original epidemiological studies was performed in the CNKI, WanFang, Cochrane Library, PubMed, and Web of Science databases. R language-based programs were employed for all statistical analyses. Odds ratios and corresponding 95% confidence intervals were calculated to estimate the effects of the variant allele on gestational diabetes risk.

Results: A summary of the estimates for the C677T polymorphism showed that the exposure cohorts were prone to gestational diabetes by a greater magnitude than the control groups. Further subgroup analysis by ethnicity showed that the Asians carrying the variant T allele were more susceptible to this pregnancy disorder. However, the pathogenic effect was not evident in the non-Asian subgroup. For the A1298C polymorphism, no statistical significance could be detected.

Conclusion: This meta-analysis suggests that the T allele of the MTHFR gene C677T polymorphism tends to increase gestational diabetes susceptibility, especially for Asians. However, the A1298C polymorphism is not associated with an increased risk of this crippling pregnancy disorder.

Keywords: Gestational diabetes mellitus; MTHFR; Meta-analysis; Polymorphism.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Diabetes, Gestational* / epidemiology
  • Diabetes, Gestational* / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Prevalence

Substances

  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)