To investigate effects of methyleneterahydrofolate reductase (MTHFR) gene polymorphism and serum folic acid level on pregnant women with gestational diabetes mellitus (GDM) and their pregnancy outcomes.

A total of 568 pregnant women with GDM who underwent prenatal examination in Qingdao Chengyang People′s Hospital from December 2016 to December 2018 were selected as research objects, and they were included into GDM group. A total of 674 healthy pregnant women who underwent prenatal examination in the same period and same hospital were included into control group. Genotypes at locus C677T and A1298C of MTHFR gene in all subjects were analyzed by fluorescent quantitative polymerase chain reaction (fqPCR), meanwhile, their serum folic acid levels were detected. The alleles and genotype distributions of C677T and A1298C loci of MTHFR gene between two groups, also genotype distribution of C677T locus between pregnant women with different pregnancy outcomes in GDM group were compared by chi-square test. Serum folic acid levels between pregnant women with different pregnancy outcomes in GDM group were compared by independent-samples t test, one-way ANOVA and least significant difference (LSD)-t test were used to compare serum folic acid levels of subjects with 3 genotypes of MTHFR gene C667T loci within and between two groups. The predictive value of GDM through different genotypes of C667T locus combined with serum folic acid level were analyzed by receiver operating characteristics (ROC) curve. The procedures followed in this study were approved by the Ethics Committee of Qingdao Chengyang People′s Hospital [Approval No. (2015) Ethics Lot No. (11)]. All subjects signed the informed consents.

① The frequency of allele C at C667T locus of MTHFR gene in GDM group was significantly higher than that in control group (70.9% vs 61.5%, χ²=24.483, P<0.001), and the genotype of this locus was mainly CC, while that of control group was mainly CT. There were no significant differences in distribution of alleles (A/C) and genotypes (AA/AC/CC) of MTHFR gene A1298C locus between two groups (all P>0.05), and A allele and AA genotype were dominant in both groups. ② The results in both groups showed that the differences of serum folic acid levels of the subjects with CC, CT and TT genotype at C667T loci of MTHFR gene was statistically significant (P<0.05), and serum folic acid level of subjects with CC genotype was significantly higher than that with TT genotype, and the difference was statistically significant (P<0.001). ③ Serum folic acid levels of subjects with CC, CT and TT genotypes at C667T locus of MTHFR gene in GDM group were (16.4±2.4) nmoL/L, (14.6±3.8) nmoL/L and (12.4±3.1) nmoL/L, which were significantly lower than those of (20.4±2.5) nmoL/L, (18.5±3.4) nmoL/L and (16.3±3.0) nmoL/L in control group, and the differences were statistically significant (t=28.040, 19.292, 22.869; all P<0.001). ④ The area under the ROC curve for prediction of GDM by different genotypes of MTHFR gene C667T locus combined with serum folic acid level was 0.816 (P<0.05). ⑤ The CC genotype frequency of MTHFR gene C667T locus and serum folic acid level of subjects with adverse pregnancy outcomes in GDM group were 32.5% and (13.3±4.2) nmoL/L, which were significantly lower than those of 42.3% and (15.9±4.0) nmoL/L of subjects without adverse pregnancy outcomes, and the TT genotype frequency (25.3%) was significantly higher than that of subjects without adverse pregnancy outcomes (17.8%), and the differences were statistically significant (χ²=5.626, P=0.018; t=7.446, P<0.001; χ²=4.680, P=0.031).

Proportion of CC genotype at MTHFR gene C667T locus was higher in pregnant women with GDM, and their serum folic acid level was lower than that of healthy pregnant women. Genotype at MTHFR gene C667T locus and serum folic acid level were associated with pregnancy outcome of GDM pregnant women.