Serum folate mediates the associations of MTHFR rs1801133 polymorphism with blood glucose levels and gestational diabetes mellitus in Chinese Han pregnant women

Abstract

This study aimed to explore the mediation effects of one-carbon metabolism (OCM) related nutrients on the association between MTHFR rs1801133 polymorphism and gestational diabetes mellitus (GDM). Folate, vitamin B12 (B12), and homocysteine (Hcy) were measured in the serum of 1254 pregnant women. Linear and logistic regressions were used to estimate the associations of OCM nutrients and MTHFR rs1801133 polymorphism with blood glucose levels and GDM risk. Mediation analysis was applied to test the mediation effects of folate, B12, and Hcy on the association of MTHFR rs1801133 polymorphism with blood glucose concentrations and GDM. Pregnant women with MTHFR rs1801133 CC genotype had higher serum folate (10.75 vs. 8.90 and 9.40 ng/mL) and lower serum Hcy (4.84 vs. 4.93 and 5.20 μmol/L) than those with CT and TT genotypes. Folate concentrations were positively associated with fasting plasma glucose (FPG), 1-h plasma glucose (1-h PG), 2-h plasma glucose (2-h PG), and GDM risk. B12 levels were negatively correlated with FPG and GDM. Although no direct association was found between MTHFR rs1801133 genotypes and GDM, there were significant indirect effects of MTHFR rs1801133 CC genotype on FPG (β: 0.005; 95% CI: 0.001, 0.013), 1-h PG (β: 0.006; 95% CI: 0.001, 0.014), 2-h PG (β: 0.007; 95% CI: 0.001, 0.015), and GDM (β: 0.006; 95% CI: 0.001, 0.014) via folate. In conclusion, serum folate mediates the effect of MTHFR rs1801133 on blood glucose levels and GDM. Our findings potentially provide a feasible GDM prevention strategy via individualized folate supplementation according to the MTHFR genotypes.

Periconceptional Folic Acid Only Versus Multiple Micronutrients Containing Folic Acid and Association with Gestational Diabetes Mellitus — Beijing Municipality, China, 2017–2021

“…WHO guidelines do not recommend promoting MMFA in pregnant women due to insufficient evidence of its benefits for neonatal survival, growth, or cognitive function compared to FAO. Additionally, MMFA supplementation may pose an increased economic burden for pregnant women (9). Although we did not investigate the specific nutrient contents and doses of MMFA, our results support prioritizing FAO supplementation for GDM prevention.…”

“…The findings indicated that MMFA supplementation primarily affected FPG levels, increasing the risk of developing GDM. Previous studies have demonstrated a relationship between vitamin B12 levels and FPG; however, no significant associations were observed between vitamin B12 and either 1 h PG or 2 h PG ( 10 ). This may suggest that FPG serves as a more sensitive indicator for GDM diagnosis and predicting risk factors.…”

Serum Folate and Vitamin B12 Modify the Associations of N6AMT1 Genetic Variants with Gestational Diabetes Mellitus: A Cross-Sectional Study in Chinese Pregnant Women

“…The study design has been described in our previous studies. 6 , 10 In brief, a total of 1505 pregnant women who underwent GDM screening between 24–28 weeks of gestation were recruited according to the following criteria: (1) older than 18 years; (2) have lived in Tianjin for one year and plan to live in Tianjin for the next six years (3) have no history of pre-pregnancy diabetes or previous GDM. Of the 1505 pregnancies, 202 were excluded for various reasons, such as being from ethnic minorities (n = 105), not having GDM (n = 38) and OCM results (n = 33), and missing covariate results (n = 26).…”

“…3 Recent studies have shown that environmental pollutants (such as arsenic and air pollution) and nutrients involved in the one-carbon metabolism (OCM) pathway may be essential in GDM. [6][7][8][9][10] Our previous study indicated that genetic variants in N-6-adenine-specific DNA methyltransferase 1 (N6AMT1) were associated with arsenic methylation metabolism. In addition, they can interact to affect GDM occurrence in the Chinese population.…”

Association between MTHFR gene C677T polymorphism and gestational diabetes mellitus in Chinese population: a meta-analysis

“…Some studies have demonstrated that the MTHFR gene C677T polymorphism is closely related to the risk of diabetes mellitus (DM) ( 14 , 15 ). Some investigators also revealed that the C-T mutation in the MTHFR C677T gene might lead to increased susceptibility to GDM ( 16 , 17 ). However, whether the MTHFR gene C677T polymorphism leads to an increased risk of GDM in the Chinese population remains controversial.…”