Single-nucleotide polymorphisms in genes involved in folate metabolism or selected other metabolites and risk for gestational diabetes mellitus.

BACKGROUND

There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus (GDM), and the correlation between genetic factors related to folic acid metabolism pathways and GDM remains to be revealed.

AIM

To examine the association between single-nucleotide polymorphisms (SNPs) of enzyme genes in the folate metabolite pathway as well as that between GDM-related genes and risk for GDM.

METHODS

A nested case-control study was conducted with GDM cases ( = 412) and healthy controls ( = 412). DNA was extracted blood samples and SNPs were genotyped using Agena Bioscience's MassARRAY gene mass spectrometry system. The associations between different SNPs of genes and the risk for GDM were estimated using logistic regression models. The generalized multi-factor dimensionality reduction (GMDR) method was used to analyze gene-gene and gene-environment interactions using the GMDR 0.9 software.

RESULTS

The variation allele frequency of melatonin receptor 1B () rs10830963 was higher in the GDM group than in controls ( < 0.05). rs10830963 mutant G was associated with risk for GDM [adjusted odds ratio (aOR): 1.43; 95% confidence interval (95%CI): 1.13-1.80] in the additive model. rs10830963 GG + GC was significantly associated with the risk for GDM (aOR: 1.65; 95%CI: 1.23-2.22) in the dominant model. The two-locus model of rs10830963 and rs4721 was the best model ( < 0.05) for gene-gene interactions in the GMDR results. The high-risk rs10830963 × rs4721 type of interaction was a risk factor for GDM (aOR: 2.09; 95%CI: 1.49-2.93).

CONCLUSION

This study does not find an association between SNPs of folate metabolic enzymes and risk for GDM. The G mutant allele of rs10830963 is identified as a risk factor for GDM in the additive model, and there may be gene-gene interactions between rs10830963 and rs4721. It is conducive to studying the causes of GDM and provides a new perspective for the precise prevention of this disease.