Serum folate mediates the associations of <i>MTHFR</i> rs1801133 polymorphism with blood glucose levels and gestational diabetes mellitus in Chinese Han pregnant women
Yunguo Wang, Yiyun Wang, Yao Sun, Naijian Zhang, Xiaoshan Liang, Suhui Luo, Li-Rong Dai, Chao Sun, Yun‐Gui Yang, Shuying Li, Xumei Zhang, Qiang Zhang
Abstract
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 B 12 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, vitamin B 12 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 v . 8·90 and 9·40 ng/ml) and lower serum Hcy (4·84 v . 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. Vitamin B 12 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 individualised folate supplementation according to the MTHFR genotypes.