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

Shuying Li,Juan Liu,Chen Li,Qiang Zhang,Xiubiao Tian,Naijun Tang,Hongjuan Liu,Xumei Zhang,Jing Li,Xilin Yang,Weiqin Li,Xueli Yang,Huihuan Liu,Chunhua Wang,Yiyun Wang,Liwen Zhang,Junhong Leng

doi:10.3390/nu14061169

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.

Highlights

Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, is currently the most common medical complication
We found that serum folate concentrations were positive, whereas serum B12 concentrations were negatively associated with the risk of gestational diabetes mellitus (GDM)
We found that serum folate levels are positively correlated with blood glucose levels and significantly associated with GDM risk in a dose-response manner

Summary

Introduction

Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, is currently the most common medical complication. Aside from its short-term adverse consequences, GDM brings long-term negative effects for both mothers and their offspring, notably, a higher risk of developing type 2 diabetes mellitus for mothers after pregnancy [2]. It highlights the importance of identifying risk factors related to GDM and developing effective prevention strategies before diagnosing GDM. Since the lifestyle intervention on GDM is a limited success [3,4], it is essential to identify other risk factors to prevent GDM. Folate and vitamin B12 (B12 ) are essential micronutrients required during pregnancy

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