Polymorphisms in gene MTHFR modify the association between gestational weight gain and adverse birth outcomes

Wu, Weixiang; Luo, Dan; Ruan, Xiaolin; Gu, Chunming; Lü, Weiming; Lian, Kailing; Mu, Xiaoping

doi:10.3389/fnut.2022.919651

Cited by 7 publications

(10 citation statements)

References 44 publications

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“…An MTHFR polymorphism leads to enzyme dysfunction, possibly resulting in higher Hcy levels and disturbances in one-carbon metabolism. Thus, MTHFR gene variants have been linked to many metabolic pathologies, including gestational weight gain [ 1 ]. The MTHFR gene has 12 exons and is located on chromosome 1 (1p36.22).…”

Section: Introductionmentioning

confidence: 99%

Methylenetetrahydrofolate Reductase C677T Gene Variant in Relation to Body Mass Index and Folate Concentration in a Polish Population

Wrzosek

Ślusarczyk

2022

Biomedicines

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Background: Methylenetetrahydrofolate reductase (MTHFR) is an enzyme responsible for producing an active form of folate. The MTHFR T677T genotype may have adverse health effects associated with weight gain and a reduction in folate availability. Aim: In this study, we examined the influence of the MTHFR C677T variant on BMI and determined its role as a risk factor for obesity. We also assessed the relationships between the MTHFR C677T genotype and folate and vitamin B12 concentrations in subjects before and after radical weight loss. Methods: The study group consisted of 1712 Caucasian adults of Polish nationality with a wide range of body mass indexes (BMIs). DNA was extracted from the blood, and the C677T variant was tested with RFLP-PCR and real-time-PCR. Results: There was no significant influence found for the MTHFR 677 TT genotype on BMI or the obesity risk in codominant, dominant or recessive inheritance models. Individuals with obesity and the TT genotype had significantly lower folate concentrations. After radical weight reduction, the impact of the risk genotype, as well as homeostasis between folate and vitamin B12 in TT homozygotes, seems to be attenuated. Conclusion: Although the MTHFR 677TT genotype is not directly related to a higher BMI in Polish adults, it has a detrimental effect on folate concentrations in individuals with high BMI values.

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Section: Introductionmentioning

confidence: 99%

Methylenetetrahydrofolate Reductase C677T Gene Variant in Relation to Body Mass Index and Folate Concentration in a Polish Population

Wrzosek

Ślusarczyk

2022

Biomedicines

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“…30 The interaction between C677T polymorphisms and obesity in patients with type 2 diabetes was also 0.05-0.76). 14 Similarly, our previous studies had indicated that pregnant women who were obese, with the CT þ TT genotype, were 2.40 times more likely to have GDM, whereas no significant association was observed in those with the CC genotype. 31 In addition, an…”

Section: Discussionmentioning

confidence: 73%

“…Heterozygous, homozygous, dominant, recessive, and additive models were used to explore the associations between genetic polymorphisms and adverse birth outcomes. To analyse the potential interaction effects of genetic variants on the association between HbA1c levels and adverse birth outcomes, the participants were divided into non‐mutated and mutated groups for better statistical power, similar to previous studies 14,15 . The likelihood ratio test was used to calculate the p ‐value for multiplicative interactions, among which the differences in the likelihood scores of the two models with and without the interaction term of genotypes and HbA1c levels were compared.…”

Section: Methodsmentioning

confidence: 99%

Interaction effects of MTHFR C677T and A1298C polymorphisms with maternal glycated haemoglobin levels on adverse birth outcomes

Wu,

Luo,

et al. 2024

Diabetes Metabolism Res

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AimsThe role of maternal genetic factors in the association between high glycated haemoglobin (HbA1c) levels and adverse birth outcomes remains unclear.Materials and MethodsIn this study, the maternal HbA1c levels of 5108 normoglycemic pregnant women in China were measured, and A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were genotyped.ResultsElevated HbA1c levels during the second trimester were associated with increased risks of macrosomia, large‐for‐gestational age (LGA), preterm birth (PTB), and reduced gestational age (p < 0.05). Pregnant women with MTHFR A1298C AA or C677T CT + TT genotypes were susceptible to adverse pregnancy outcomes related to HbA1c levels. Among pregnant women with the A1298C AA genotype, each standard deviation (SD) increase in HbA1c levels increased the risk of PTB by 1.32‐times and reduced the gestational age by 0.11 weeks (p < 0.05). For MTHFR C677T CC + TT genotype carriers, higher HbA1c levels were associated with 1.49‐, 1.24‐, and 1.23‐times increased risks of macrosomia, LGA, and PTB, respectively (p < 0.05). A U‐shaped curve for PTB risk in relation to HbA1c levels was observed among the C677T CC + TT participants, with a cut‐off value of 4.58%. Among subjects with the A1298C AA genotype combined with the C677T CT + TT genotype, each SD increase in HbA1c levels was associated with 1.40 and 1.37‐times increased risks of LGA and PTB, respectively.ConclusionsOur findings highlight the importance of glycaemic control during pregnancy and the potential impact of genetic factors on birth outcomes. However, further large‐scale studies are required to confirm these findings.

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“…There is increasing concern regarding whether genetic polymorphisms within lipid metabolism or nutritional factors in pregnant women are associated with the development of pregnancy outcomes [ 11 ]. Among them, methylenetetrahydrofolate reductase (MTHFR) plays an important role in the enzymatic process for maintaining folate metabolism and homocysteine methylation, which are considered risk factors during pregnancy [ 12 – 14 ]. The C677T and A1298C variants in MTHFR are two common single nucleotide polymorphisms (SNPs), and these variants have also been associated with several pregnancy complications, but the results were different.…”

Section: Introductionmentioning

confidence: 99%

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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Polymorphisms in gene MTHFR modify the association between gestational weight gain and adverse birth outcomes

Cited by 7 publications

References 44 publications

Methylenetetrahydrofolate Reductase C677T Gene Variant in Relation to Body Mass Index and Folate Concentration in a Polish Population

Methylenetetrahydrofolate Reductase C677T Gene Variant in Relation to Body Mass Index and Folate Concentration in a Polish Population

Interaction effects of MTHFR C677T and A1298C polymorphisms with maternal glycated haemoglobin levels on adverse birth outcomes

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

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