Associations of Maternal rs1801131 Genotype in MTHFR and Serum Folate and Vitamin B12 with Gestational Diabetes Mellitus in Chinese Pregnant Women

Abstract

Circumstantial evidence links one-carbon metabolism (OCM) related nutrients, such as folate and vitamin B12, with gestational diabetes mellitus (GDM). However, few studies have evaluated the combined effects of these nutrients with OCM related gene polymorphisms on GDM. This study investigated whether OCM related genetic variants modified the associations of folate and B12 with GDM. Logistic regression was used to estimate odds ratios (ORs) for OCM related nutrients and single nucleotide polymorphisms (SNPs) in genes encoding main OCM related enzymes (MTHFR, MTR, and MTRR) on GDM. Higher folate concentrations were associated with increased GDM risk (OR: 1.59; 95% CI: 1.22, 2.13). However, higher B12 concentrations were associated with reduced GDM risk (OR: 0.76; 95% CI: 0.65, 0.92). Pregnancies with MTHFR rs1801131 G alleles had a significantly lower risk of GDM than pregnancies with T alleles (OR: 0.65; 95% CI: 0.47, 0.91) under the dominant model. The genotype-stratified analysis revealed the association between folate and GDM (OR: 1.66, 95% CI: 1.20, 2.30) or B12 and GDM (OR: 0.80, 95% CI: 0.65, 0.98) was more evident in pregnancies with TT genotype. Higher folate and lower B12 are associated with GDM. Pregnancies with MTHFR rs1801131 TT genotype are more susceptible to OCM nutrient-related GDM.

Vitamin B12 status and folic acid/vitamin B12 related to the risk of gestational diabetes mellitus in pregnancy: a systematic review and meta-analysis of observational studies

“…Among the 10 studies, there were 4 prospective cohort studies with sample sizes ranging from 180 to 4,746 [ 17 , 24 , 25 , 35 ], 2 were cross-sectional studies including a total of 1,319 individuals [ 18 , 26 ], and 4 were case–control studies [ 22 , 23 , 27 , 36 ]. Of the 10 studies, 5 were performed in China [ 18 , 23 , 25 – 27 ], 3 in India [ 17 , 18 , 35 ], 1 in Australia [ 36 ], and two in Britain [ 22 , 24 ]. The cutoff values of vitamin B12 were not uniform and included studies that primarily used 150 pmol/L–220 pmol/L.…”

“…The NOS was used to assess the quality of studies, and scores ≥ 6 were considered high quality. 8 of the studies had a score of 7 [ 17 , 18 , 22 , 24 – 27 , 36 ], and the remaining 2 studies had a score of 4 [ 23 , 35 ]. Regarding the GDM criteria, 5 studies used the International Association of Diabetes and Pregnancy Study Groups (IADPSG) [ 23 – 27 ], 3studies used the WHO1999 [ 17 , 18 , 22 ], 1used the WHO2016 criteria [ 36 ], and 1 was based on the criteria of Carpenter and Coustan [ 35 ].…”

“…8 of the studies had a score of 7 [ 17 , 18 , 22 , 24 – 27 , 36 ], and the remaining 2 studies had a score of 4 [ 23 , 35 ]. Regarding the GDM criteria, 5 studies used the International Association of Diabetes and Pregnancy Study Groups (IADPSG) [ 23 – 27 ], 3studies used the WHO1999 [ 17 , 18 , 22 ], 1used the WHO2016 criteria [ 36 ], and 1 was based on the criteria of Carpenter and Coustan [ 35 ]. The quality of the included literature was medium, and the results were shown in Supplementary Table 1 .…”

“…Wang et al [ 23 ], Sukumar et al [ 22 ] and Krishnaveni et al [ 17 ] conducted case–control and cohort studies with blood samples from 1,129 pregnant women drawn in mid-late pregnancy and showed that maternal vitamin B12 insufficiency increased the risk of GDM. In other terms, higher levels of vitamin B12 reduced the risk of GDM [ 18 , 26 , 27 ]. In contrast, Chen et al [ 25 ] performed a prospective cohort study in China during the first trimester and indicated that women with high levels of vitamin B12 may be at an increased risk of GDM; however, a cohort study involving more than 4,000 participants in the Britain revealed an increased risk due to vitamin B12 deficiency in early pregnancy [ 24 ].…”

“…Serum folic acid and vitamin B12 (folic acid/vitamin B12) imbalances are more strongly associated with GDM [ 26 ]. Folic acid is involved in DNA methylation and biosynthesis of nucleic acids and proteins required for cell replication and fetal growth and is an essential micronutrient during pregnancy [ 27 ]. Recently, only 3 systematic reviews investigated the association between vitamin B12 paired with folic acid and GDM [ 28 – 30 ].…”