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

Purpose: This study aimed to explore the association between N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) single nucleotide polymorphisms (SNPs) and gestational diabetes mellitus (GDM) and the modification of the relationship by folate and vitamin B 12 .Methods: A cross-sectional study involving 1303 pregnant women (262 GDM and 1041 non-GDM) was performed in Tianjin, China.Nine SNPs in N6AMT1 were genotyped, and serum folate, vitamin B 12 , and homocysteine (Hcy) levels were measured.The logistic regression models determined the odds ratios (ORs) for SNPs in N6AMT1 and the gene-nutrition interactions on GDM.Results: N6AMT1 rs7282280, rs1048546, and rs1997605 were related to GDM under the dominant model after adjusting for multiple covariates.Individuals carrying the N6AMT1 rs7282280 TC/TT genotypes had a lower risk of developing GDM, regardless of serum folate and vitamin B 12 levels.However, rs1048546 TG/GG genotypes were associated with lower GDM risk when serum folate ≥ 6.0 ng/mL.Pregnancies with the risk genotypes in N6AMT1 and higher serum folate or lower vitamin B 12 are more prone to GDM.The study also showed a statistically significant additive interaction between N6AMT1 rs1997605 GG genotypes and lower vitamin B 12 (RERI: 2.54; 95% CI: 0.17, 4.92).Conclusion: SNPs in N6AMT1 were found to be associated with GDM, and serum folate and vitamin B 12 levels can modify their associations.