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

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.

[1]  Yang Zheng,et al.  Homocysteine level and gestational diabetes mellitus: a systematic review and meta-analysis , 2021, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[2]  C. Fall,et al.  Association of maternal vitamin B12 and folate levels in early pregnancy with gestational diabetes: a prospective UK cohort study (PRiDE study) , 2021, Diabetologia.

[3]  Liangpo Liu,et al.  Joint effect of urinary arsenic species and serum one-carbon metabolism nutrients on gestational diabetes mellitus: A cross-sectional study of Chinese pregnant women. , 2021, Environment international.

[4]  Xinyin Jiang,et al.  One carbon metabolism and early development: a diet-dependent destiny , 2021, Trends in Endocrinology & Metabolism.

[5]  D. Kiel,et al.  Genetic variants modify the associations of concentrations of methylmalonic acid, vitamin B-12, vitamin B-6, and folate with bone mineral density. , 2021, The American journal of clinical nutrition.

[6]  P. Rheeder,et al.  No Association Between ADIPOQ or MTHFR Polymorphisms and Gestational Diabetes Mellitus in South African Women , 2021, Diabetes, metabolic syndrome and obesity : targets and therapy.

[7]  Z. Pausova,et al.  [6S]-5-Methyltetrahydrofolic Acid and Folic Acid Pregnancy Diets Differentially Program Metabolic Phenotype and Hypothalamic Gene Expression of Wistar Rat Dams Post-Birth , 2020, Nutrients.

[8]  Weili Yan,et al.  Association of Maternal Folate and Vitamin B12 in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study , 2020, Diabetes care.

[9]  Naijun Tang,et al.  Interactions of arsenic metabolism with arsenic exposure and individual factors on diabetes occurrence: Baseline findings from Arsenic and Non-Communicable disease cohort (AsNCD) in China. , 2020, Environmental pollution.

[10]  K. Khunti,et al.  Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis , 2020, BMJ.

[11]  Z. Fu,et al.  Association of maternal folate status in the second trimester of pregnancy with the risk of gestational diabetes mellitus , 2019, Food science & nutrition.

[12]  A. Baccarelli,et al.  Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium , 2019, Diabetes Care.

[13]  Xiaoyan Wu,et al.  Joint effects of folate and vitamin B12 imbalance with maternal characteristics on gestational diabetes mellitus , 2019, Journal of diabetes.

[14]  A. Daponte,et al.  Vitamin B12 insufficiency is associated with increased risk of gestational diabetes mellitus: a systematic review and meta-analysis , 2019, Endocrine.

[15]  P. Damm,et al.  Gestational diabetes mellitus , 2019, Nature Reviews Disease Primers.

[16]  P. Tsai,et al.  Association of dietary folate and vitamin B-12 intake with genome-wide DNA methylation in blood: a large-scale epigenome-wide association analysis in 5841 individuals. , 2019, The American journal of clinical nutrition.

[17]  Nianlan Yang,et al.  High-Dose Folic Acid Supplement Use From Prepregnancy Through Midpregnancy Is Associated With Increased Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study , 2019, Diabetes Care.

[18]  F. Hu,et al.  Prepregnancy Habitual Intakes of Total, Supplemental, and Food Folate and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study , 2019, Diabetes Care.

[19]  E. Feskens,et al.  Changes in Micronutrient Intake and Status, Diet Quality and Glucose Tolerance from Preconception to the Second Trimester of Pregnancy , 2019, Nutrients.

[20]  B. Howard,et al.  Arsenic, one carbon metabolism and diabetes-related outcomes in the Strong Heart Family Study. , 2018, Environment international.

[21]  D. Jensen,et al.  Lifestyle Intervention in Danish Obese Pregnant Women With Early Gestational Diabetes Mellitus According to WHO 2013 Criteria Does Not Change Pregnancy Outcomes: Results From the LiP (Lifestyle in Pregnancy) Study , 2018, Diabetes Care.

[22]  J. Lovegrove,et al.  An update on vitamin B12-related gene polymorphisms and B12 status , 2018, Genes & Nutrition.

[23]  K. Godfrey,et al.  High folate and low vitamin B12 status during pregnancy is associated with gestational diabetes mellitus. , 2017, Clinical nutrition.

[24]  D. Marchioni,et al.  Genetic Variants Involved in One-Carbon Metabolism: Polymorphism Frequencies and Differences in Homocysteine Concentrations in the Folic Acid Fortification Era , 2017, Nutrients.

[25]  P. Stover,et al.  Folate rescues vitamin B12 depletion-induced inhibition of nuclear thymidylate biosynthesis and genome instability , 2017, Proceedings of the National Academy of Sciences.

[26]  A. Horimoto,et al.  MTRR rs326119 polymorphism is associated with plasma concentrations of homocysteine and cobalamin, but not with congenital heart disease or coronary atherosclerosis in Brazilian patients , 2016, International journal of cardiology. Heart & vasculature.

[27]  V. Patel,et al.  Vitamin B12 Status among Pregnant Women in the UK and Its Association with Obesity and Gestational Diabetes , 2016, Nutrients.

[28]  N. Oliver,et al.  Gestational diabetes mellitus: does an effective prevention strategy exist? , 2016, Nature Reviews Endocrinology.

[29]  Maochun Wang,et al.  A novel three-round multiplex PCR for SNP genotyping with next generation sequencing , 2016, Analytical and Bioanalytical Chemistry.

[30]  F. Tao,et al.  Folic Acid Supplement Intake in Early Pregnancy Increases Risk of Gestational Diabetes Mellitus: Evidence From a Prospective Cohort Study , 2016, Diabetes Care.

[31]  Wen-Xing Li,et al.  Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency , 2015, Nutrients.

[32]  David C Christiani,et al.  Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. , 2015, Biostatistics.

[33]  N. Shaik,et al.  Evaluation of Gestational Diabetes Mellitus Risk in South Indian Women Based on MTHFR (C677T) and FVL (G1691A) Mutations , 2015, Front. Pediatr..

[34]  C. Lopes,et al.  Folate and folic acid in the periconceptional period: recommendations from official health organizations in thirty-six countries worldwide and WHO , 2015, Public Health Nutrition.

[35]  R. Steegers-Theunissen,et al.  The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism. , 2013, Human reproduction update.

[36]  Huixia Yang.  Diagnostic criteria for gestational diabetes mellitus (WS 331-2011). , 2012, Chinese medical journal.

[37]  J. Fletcher,et al.  Genetic association study of putative functional single nucleotide polymorphisms of genes in folate metabolism and spina bifida. , 2009, American journal of obstetrics and gynecology.

[38]  D. Bhat,et al.  Low plasma vitamin B12 in pregnancy is associated with gestational ‘diabesity’ and later diabetes , 2009, Diabetologia.

[39]  M. Hirata,et al.  Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women , 2008, European Journal of Clinical Nutrition.

[40]  D. Grobbee,et al.  Estimating interaction on an additive scale between continuous determinants in a logistic regression model. , 2007, International journal of epidemiology.

[41]  J. Selhub,et al.  A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[42]  S. Shapiro,et al.  Periconceptional folic acid exposure and risk of occurrent neural tube defects. , 1993, JAMA.