Associations Between Gestational Diabetes Mellitus Risk and Folate Status in Early Pregnancy and MTHFR C677T Polymorphisms in Chinese Women

Abstract

Purpose

Red blood cell (RBC) folate indicates long-term folate intake, and methylenetetrahydrofolate reductase (MTHFR) gene is the main gene affecting folate status. Increasing evidence suggests an association between gestational diabetes mellitus (GDM) and increased folate levels. Whether RBC folate concentrations in the first trimester of pregnancy or polymorphisms of MTHFR C677T (rs1801133) affect GDM risk in Chinese pregnant women remains unknown. Therefore, we analyzed the associations of RBC folate concentrations and rs1801133 polymorphisms with GDM risk among pregnant women in China.

Methods

A total of 366 women with a singleton pregnancy were followed prospectively from their first prenatal visit to delivery. RBC folate concentrations and rs1801133 polymorphisms were assessed during the first trimester of pregnancy. Binary logistic regression analyses were performed to determine the odds ratios (ORs) of GDM and 95% confidence intervals (CIs) by using the RBC folate concentration quartiles and rs1801133 polymorphisms.

Results

Participants with the TT genotype had the highest RBC folate concentrations. Those with heterozygous or homozygous variants did not have a significantly higher risk of GDM than did women with C alleles. After adjustments for covariates, women in the highest quartile for RBC folate concentration had a higher risk of GDM (adjusted OR = 2.473, 95% CI = 1.013–6.037, P = 0.047) than did those in the lowest quartile, but this association was nonsignificant after adjustment for rs1801133 polymorphisms.

Conclusion

Higher RBC folate, partly caused by MTHFR 677C→T, may be associated with increased GDM risk, even in early pregnancy. Assessing RBC folate status and appropriately supplementing folate during early pregnancy, particularly for patients with MTHFR 677C→T, may prevent GDM. Further studies with larger populations are warranted.

Keywords:

• gestational diabetes mellitus
• folic acid
• folate
• red blood cell folate
• methylenetetrahydrofolate reductase
• MTHFR

Abbreviations

GDM, gestational diabetes mellitus; MTHFR, methylenetetrahydrofolate reductase; RBC, red blood cell; FA, folic acid; FPG, fasting plasma glucose; IGT, impaired glucose tolerance; CRP, C-reactive protein; OGTT, oral glucose tolerance test; NTD, neural tube defect; HOMA-IR, homeostasis model assessment-insulin resistance; HOMA-β, homeostasis model assessment-β; SNP, single-nucleotide polymorphism.

Acknowledgments

We thank Shanghai GeneX Biotech Co., Ltd and Beijing Malt Health Management Co. Ltd for their free technical support. We also acknowledge Li ShanShan, Wang BingXin, Li BaoLei, Li Rui, Luo Haoze, Zhou Zikun, and Bao Yuanyuan, who helped with collecting anonymous data from routinely collected maternity records.

Author Contributions

All authors contributed to data analysis, article drafting, and revision. All authors approved the final version for publishing and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.