Increasing prevalence of gestational diabetes mellitus when carrying the T variant allele of the MTHFR gene C677T polymorphism: a systematic review and meta-analysis

Chen, Yanjie; Lu, Mingzhu; Nie, Jinyi; Li, Jianjun; Liu, Yu; Meng, Yijun; Sun, Xiaohan; Ji, Cheng; Zhang, Jie; Yang, Xiaoqin

doi:10.1007/s00404-021-06303-4

Cited by 8 publications

(12 citation statements)

References 39 publications

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“…Methylenetetrahydrofolate reductase A1298C polymorphism and diabetes risk: evidence from a meta-analysis T2DM [77] Association between MTHFR C677T polymorphism and diabetic nephropathy in the Chinese population: An updated meta-analysis and review DN [78] Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to diabetic nephropathy in Chinese type 2 diabetic patients: a meta-analysis T2DM and DN [79] Increasing prevalence of gestational diabetes mellitus when carrying the T variant allele of the MTHFR gene C677T polymorphism: a systematic review and meta-analysis Gestational diabetes [80] Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy risk: a meta-analysis T2DM and DN [81] A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy DR [82] Genetics of diabetic neuropathy: Systematic review, meta-analysis and trial sequential analysis DN [83] Methylenetetrahydrofolate reductase C677T polymorphism and type 2 diabetes mellitus in Chinese population: a meta-analysis of 29 case-control studies T2DM [84] Plausible relationship between homocysteine and obesity risk via MTHFR gene: a meta-analysis of 38,317 individuals implementing Mendelian randomization Obesity risk [85] Association of homocysteine with type 2 diabetes: a meta-analysis implementing Mendelian randomization approach T2DM [86] Effects of Common Polymorphisms in the MTHFR and ACE Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis DN [87] ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: a meta-analysis T2DM [88] Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and diabetic nephropathy susceptibility in patients with type 2 diabetes mellitus T2DM and DN [89] Association between MTHFR C677T polymorphism and diabetic nephropathy or diabetes mellitus risk: need for clarification of data in a recent meta-analysis T2DM and DN [90] Methylenetetrahydrofolate reductase C677T polymorphism and diabetic retinopathy risk: a meta-analysis of the Chinese population DR [91] The relationship between methylenetetrahydrofolate reductase C677T polymorphism and diabetic retinopathy: A meta-analysis in multi-ethnic groups DR [92] MTHFR gene C677T polymorphism and type 2 diabetic nephropathy in Asian populations: a meta-analysis DN [93] Genetic susceptibility to type 2 diabetes: a global meta-analysis studying the genetic differences in Tunisian populations T2DM [94] Genetic risk of type 2 diabetes in populations of the African continent: A systematic review and meta-analyses T2DM…”

Section: Study Title Associated Disease Referencementioning

confidence: 99%

Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks

2021

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The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism and protein, DNA, and RNA synthesis. The enzyme is responsible for maintaining methionine and homocysteine (Hcy) balance to prevent cellular dysfunction. Polymorphisms in the MTHFR gene, especially C677T, have been associated with various diseases, including cardiovascular diseases (CVDs), cancer, inflammatory conditions, diabetes, and vascular disorders. The C677T MTHFR polymorphism is thought to be the most common cause of elevated Hcy levels, which is considered an independent risk factor for CVD. This polymorphism results in an amino acid change from alanine to valine, which prevents optimal functioning of the enzyme at temperatures above 37 °C. Many studies have been conducted to determine whether there is an association between the C677T polymorphism and increased risk for CVD. There is much evidence in favour of this association, while several studies have concluded that the polymorphism cannot be used to predict CVD development or progression. This review discusses current research regarding the C677T polymorphism and its relationship with CVD, inflammation, diabetes, and epigenetic regulation and compares the evidence provided for and against the association with CVD.

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Section: Study Title Associated Disease Referencementioning

confidence: 99%

Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks

2021

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“…Maternal obesity is linked to an increased prevalence of CS and GDM [ 39 ]. A meta-analysis of the original epidemiological studies demonstrated that the susceptibility to GDM was higher in the C677T TT genotype, especially in Asians [ 40 ], which was further supported by a gene-nutrient interaction study based on a Chinese pregnancy cohort [ 41 ]. The difference between these two SNPs might be because A1298C non-mutated pregnant women with higher pre-BMI values are more likely to be homozygous or heterozygous mutants for the C677T polymorphism, which might be affected by the C677T mutation.…”

Section: Discussionmentioning

confidence: 92%

Maternal pre-pregnancy BMI, MTHFR polymorphisms, and the risk of adverse pregnancy outcomes in pregnant women from South China: a retrospective cohort study

Gu¹,

Wu²,

Lai³

et al. 2023

BMC Pregnancy Childbirth

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Background Increasing evidence suggests an association between maternal pre-pregnancy body mass index (pre-BMI) and adverse pregnancy outcomes. However, the effects of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on these relationships require further investigation. This study aimed to investigate whether the relationship between pre-BMI and the risk of adverse pregnancy outcomes was influenced by MTHFR gene polymorphisms. Methods A total of 5614 mother-fetus pairs were included in the study. The odds ratios (OR) of adverse pregnancy complications, including gestational diabetes mellitus (GDM), gestational hypertension (GHT), cesarean delivery (CS), and premature rupture of membranes (PROM), were estimated using adjusted logistic regression models and subgroup analysis. Results Pregnant women with higher pre-BMI values were positively related to the risk of GDM, GHT, and CS. In the subgroup analysis, underweight BMI was associated with a decreased risk of CS and GDM in pregnant women with the MTHFR A1298C AA or C677T CC genotype, while overweight/obese BMI was associated with an increased risk of GDM and CS in different MTHFR variants. Moreover, pregnant women with MTHFR A1298C AC + CC or C667T CC were found to have an increased risk of GHT in the MTHFR A1298C AA or C667T CT + TT genotype. A remarkable association was observed between the obesity group with MTHFR A1298C AC + CC (OR = 6.49, CI: 2.67–15.79) and the overweight group with the C667T CC genotype (OR = 4.72, CI: 2.13–10.45). Conclusions MTHFR gene polymorphisms exert a modifying effect on the association between maternal pre-BMI and the risk of GHT, CS, and GDM. Pregnant women with a high pre-BMI with specific MTHFR genotypes should be considered for GHT development.

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“…pancreatic b-cell insulin secretion, resulting in an increase in blood glucose levels (42). These two factors have a reciprocal causal relationship and mutually influence each other.…”

Section: Discussionmentioning

confidence: 99%

Association between MTHFR gene C677T polymorphism and gestational diabetes mellitus in Chinese population: a meta-analysis

Tan,

Chen

2023

Front. Endocrinol.

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Background and purposeThe relationship of the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with the incidence of gestational diabetes mellitus (GDM) in the Chinese population remains controversial. This study aimed to further clarify the effect of the MTHFR gene C677T polymorphism on GDM risk among Chinese pregnant women based on current evidence.MethodsSeveral databases were searched up to July 29, 2023 for relevant case-control studies. The numbers of patients with and without the T allele of the MTHFR gene C677T polymorphism in the GDM and control groups were determined, and all statistical analyses were performed by RevMan 5.3 software and STATA 15.0 software. Trial sequential analysis (TSA) was performed by TSA version 0.9 beta software to determine the required information size.ResultsA total of 17 case-control studies involving 12345 Chinese participants were included. The pooled results demonstrated that the T allele of the MTHFR gene C677T polymorphism was significantly associated with an increased risk of GDM, which was manifested by the five gene models of the MTHFR C677T polymorphism [T vs. C: odds ratio (OR)=1.59, P=0.03; TT vs. CC: OR=2.24, P<0.001; TC vs. CC: OR=1.28, P=0.05; (TT+TC) vs. CC: OR=1.55, P=0.003; TT vs. (TC+CC): OR=1.89, P<0.001]. Subgroup analysis based on the regions indicated that the significant relationship between the T allele of the MTHFR gene C677T polymorphism and an increased risk of GDM was detected only among the southern population [T vs. C: OR=1.62, P=0.09; TT vs. CC: OR=2.22, P=0.004; TC vs. CC: OR=1.17, P=0.28; (TT+TC) vs. CC: OR=1.43, P=0.03; TT vs. (TC+CC): OR=1.97, P=0.006]. TSA plots showed that the information sizes for the association between the MTHFR gene C677T polymorphism and GDM risk were sufficient in the homozygote (TT vs. CC) and recessive (TT vs. TC+CC) models.ConclusionThe MTHFR gene C677T polymorphism is closely related to susceptibility to GDM in the southern Chinese population, and the C-T mutation serves as an important genetic risk factor for GDM. More well-designed large case-control studies are needed to further confirm the above findings.

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Increasing prevalence of gestational diabetes mellitus when carrying the T variant allele of the MTHFR gene C677T polymorphism: a systematic review and meta-analysis

Cited by 8 publications

References 39 publications

Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks

Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks

Maternal pre-pregnancy BMI, MTHFR polymorphisms, and the risk of adverse pregnancy outcomes in pregnant women from South China: a retrospective cohort study

Association between MTHFR gene C677T polymorphism and gestational diabetes mellitus in Chinese population: a meta-analysis

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