Maternal Methylenetetrahydrofolate Reductase Research Articles

Maternal methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism: implications in preventing recurrent pregnancy loss.

Maternal methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism: implications in preventing recurrent pregnancy loss.

Association of Methylenetetrahydrofolate Reductase Gene Polymorphism C677T with Oocyte Number and Embryo Quality in Iraqi Infertile Women Undergoing Intracytoplasmic Sperm Injection

Background: Methylenetetrahydrofolate reductase (MTHFR) C677T is a single nucleotide polymorphism (SNP) that affects the production of 5-methyltetrahydrofolate (5-MTHF), the active folate that enables the recycling of homocysteine (Hcy) to methionine. Objective: to investigate the association between the MTHFR (C677T) polymorphism and the outcomes of intracytoplasmic sperm injection (ICSI). Methods: A prospective cohort study included 85 infertile women undergoing ICSI treatment at the High Institute of Infertility Diagnosis and Assisted Reproductive Technologies in Baghdad, Iraq. The study period extended from January 2022 to September 2023. The MTHFR C677T polymorphism genotyping was evaluated in these patients, and they were classified into three groups according to genotyping results: normal (CC), heterozygote mutated (CT), and mutated homozygote (TT). In addition, we conducted a comparative analysis of oocyte, embryo and pregnancy rates among these three groups. Results: In comparison to the CT and TT genotypes, the total number of oocytes, total embryos, mature oocytes, good-quality embryos, and pregnancy rate were all found to be significantly higher (p<0.05) in the CC genotype. Compared to the CC group, the proportion of immature oocytes and poor-quality embryos was significantly higher in the TT and CT groups (p<0.05). The rate of fertilization was comparable among the study groups. Conclusions: The maternal MTHFR C677T polymorphism is linked to oocyte number, maturity, total embryo, embryo quality, and pregnancy in ICSI. In light of this, MTHFR polymorphism in our community offers useful data regarding the success of ICSI.

Association of Methylenetetrahydrofolate Reductase Gene Polymorphism in Mothers With Adverse Clinical Outcomes in Neonates.

The presence of polymorphic methylenetetrahydrofolate reductase(MTHFR) in mothers poses a risk for numerous detrimental outcomes in neonates. The present study investigated the association of maternal MTHFR A1298C and C677T single nucleotide polymorphisms (SNPs) with the clinical outcomes in their neonates. The cross-sectional study included 60 mothers and their neonates. Blood samples from mothers were analyzed for MTHFR A1298C and C677T SNP genotyping by real-time polymerase chain reaction. Clinical details of mothers and neonates were documented. Study groups were stratified based on wild, heterozygous, and mutant genotypes for the respective polymorphisms observed in mothers. Multinomial regression was applied for the association, followed by gene model formulation to estimate the impact of the genetic variants on the outcomes. The frequency percentages of mutant CC1298 and TT677 genotypes were 25% and 8.06%, respectively, and the mutant allele frequencies (MAF) were 42.5% and 22.5%. Percentages of adverse outcomes such as intrauterine growth restriction, sepsis, anomalies, and mortality were higher in neonates born to mothers with homozygous mutant genotypes. Maternal C677T MTHFR SNPs revealed a significant association with neonatal anomalies (p = 0.001). The multiplicative risk model depicted OR (95% CI) for CT vs. CC+TT as 3.0 (95% CI: 0.66-13.7), and for TT vs. CT+CC was 15 (95% CI: 2.01-112.12). The C677T SNP in mothers predicted a dominant model for neonatal death (OR (95% CI): 5.84 (0.57-60.03), p = 0.15), whereas the A1298C reported recessive model for 1298CC mothers (OR (95% CI): 11 (1.05-115.5), p = 0.02). Both the genotypes assumed a recessive model for adverse neonatal outcomes: OR (95%CI) for CC vs. AA+ACwas 3.2 (0.79-12.9, p = 0.1), and for TT vs. CC+CT was 5.48 (0.57-175.7, p = 0.2). The risk for sepsis in neonates was nearly six times higher in those born from mothers with homozygous CC1298 and TT677 than in the wild and heterozygous variants. Mothers with C677T and A1298C SNPs are highly susceptible to adverse outcomes in their neonates. Hence, screening the SNPs during the antenatal period can purposefully serve as a better predictive marker, following which proper clinical management could be planned.

MTHFR C677T POLYMORPHISM: A MATERNAL RISK FACTOR FOR HAVING A MENTALLY RETARDED CHILD IN INDIA

The present case-control study examined the association of genetic polymorphism with mental retardation. One common polymorphism (SNPs), C677T in the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene involved in folate metabolism, is known to lower the activity of this enzyme. One hundred sixty mothers (with MR and normal children), from the Eastern Uttar Pradesh, India, were genotyped for MTHFR C677T SNP. Significant association with this SNP was detected, more specifically, with T allele in the mothers of MR children. The relative risk of T (C677T) in mothers for MR-affected pregnancy was 3 (OR 3.179, 95% CI 1.40-7.78). The results indicated statistically significant associations between maternal MTHFR C677T polymorphism and congenital heart defects in foetus under different genetic models.

Maternal MTHFR Gene Polymorphisms and the Risk of Cancer Disease

The etiology of Cancer disease has been related to polymorphisms in the genes encoding the folate metabolizing enzymes methylenetetrahydrofolate reductase (MTHFR). Despite several studies having linked Down syndrome to genetic factors, the specific etiology remained unclear. Our study aimed to investigate maternal MTHFR gene polymorphism and its risk of Cancer disease. This study was done during the period November 2019 and October 2020. We investigated 132 (80 newborn babies with and 52 healthy individuals as a control) their ages ranging from 14 to 22 years old at (Hiwa Institute for Deaf and Mutes) in Arbil city, Kurdistan/Iraq. Our study revealed that maternal genetic polymorphism of MTHFR EXON8-1261-1395 gene among all samples was only seen among patient samples rather than the control group were detected by PCR. In addition, sequencing results showed the presence of some mutation among polymorphism group (Deletion A) in two different nucleotide regions and there are two sites of (Substation C to T) in other nucleotide regions (105-108). The present finding supports the association of maternal MTHFR genotype polymorphism and risk factors and is associated with the presence of many abnormalities such as Cancer disease in the offspring. We suggest that the identification of maternal MTHFR genotype polymorphism should be taken concern and should be used as a critical marker for diagnosis of DS in babies.

Maternal MTHFR 677C>T, 1298A>C gene polymorphisms and risk of offspring aneuploidy.

The objective was to investigate the association between maternal methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, crucial for DNA methylation, and risk of offspring aneuploidy. MTHFR gene polymorphisms 677C>T and 1298A>C were determined by polymerase chain reaction based method, in 163 women with offspring aneuploidy and 155 women with healthy children. Five genetic models were used to assess risk, according to the type of aneuploidy and the age of women at conception. MTHFR 677TT genotype and T allele were significantly more prevalent among women with offspring aneuploidy, with an increased risk of aneuploidy demonstrated under a recessive (OR 3.499), homozygote (OR 3.456) and allele contrast model (OR 1.574). The more prominent association was found with sex chromosome aneuploidies and trisomy 13/18, and also in women ≤35years at conception. No association was observed between 1298A>C polymorphism and risk of offspring aneuploidy, although synergistic effect of two polymorphisms increase the risk of aneuploidy, primarily amplifying the 677T allele effects (p<0.001). Maternal MTHFR 677C>T gene polymorphism, alone or in combination with another 1298A>C polymorphism, appears to be a substantial risk factor for offspring aneuploidy in Montenegro population, especially for sex chromosome aneuploidies and trisomy 13/18, and among younger women.

Study on the polymorphism of methylenetetrahydrofolate reductase C677T gene as the genetic predisposition of congenital heart disease in North Indian population

Background: The etiology of congenital heart disease (CHD) is still not known properly. The variant alleles in the methylenetetrahydrofolate reductase (MTHFR) C677T gene help in elevating the serum homocysteine level which is an independent predisposing factor for generating CHD. Aims and Objectives: The aim of the present study was to analyze the role of polymorphism of MTHFR C677T gene polymorphisms in CHD patients of Varanasi, Uttar Pradesh, North India. Materials and Methods: The present study included 36 unrelated CHD patients along with their parents. At the same time, 40 healthy control samples were included in the study. MTHFR 677 C&gt;T genotype was identified by polymerase chain reaction followed by restriction digestion restriction fragment length polymorphism mechanism. Results: There was a significant difference observed in MTHFR C677T gene polymorphism between the cases and controls (P&lt;0.001). Among the different etiological factors, increased maternal age, family history, and teratogens are the major ones. Maternal MTHFR C677T genotype and periconceptional folate intake have important ascription toward CHD formation. Conclusion: The results designate that MTHFR C677T polymorphism has a substantial association with the development and progression of CHDs. Folate supplementation might be the probable management strategy for reducing the risk of CHDs as maternal MTHFR C677T polymorphism has an important contribution.

Association between Maternal and Fetal MTHFR C677T and MTRR A66G Polymorphisms with the Risk of NTDs: A Systematic Review and Meta-Analysis Study

Background: Neural tube defects (NTDs) are classed as multifactorial birth defects of the brain and spinal cord that arise during embryonic development. Although the etiology is not well understood, NTDs are reported to be prevented by maternal folic acid supplementation before and during early pregnancy. This meta-analysis study aimed to assess the association between fetal and maternal methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with the risk of NTDs. Methods: The PubMed, Scopus, and Springer Link databases were searched (from March 2000 to November 2020) for the literature on the association between MTHFR C677T and MTRR A66G polymorphisms with the risk of NTDs. Results: In total, 33 studies were reviewed in the present study, and it was revealed that, unlike MTRR A66G polymorphism, MTHFR C677T was statistically associated with the risk of NTDs in the overall population. The results of subgroup analysis showed that the Indian subcontinent subgroup with maternal MTHFR C677T polymorphism and the European subgroup with fetal MTHFR C677T polymorphism was significantly susceptible to NTDs. Conclusion: The obtained results revealed that, unlike MTRR A66G, maternal and fetal MTHFR C677T polymorphism was significantly associated with NTDs. Subgroup analysis also demonstrated that folic acid deprivation can be considered the main cause of MTHFR C677T polymorphism in some areas.

Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism and Infant's Anthropometry at Birth.

Identification of causal factors that influence fetal growth and anthropometry at birth is of great importance as they provide information about increased risk of disease throughout life. The association between maternal genetic polymorphism MTHFR(677)C>T and anthropometry at birth has been widely studied because of its key role in the one-carbon cycle. MTHFR(677) CT and TT genotypes have been associated with a greater risk of low birth weight, especially in case of deficient intake of folic acid during pregnancy. This study aimed to analyze the association between the maternal MTHFR(677)C>T genetic polymorphism and anthropometry at birth in a population with adequate folate consumption. We included 694 mother–newborn pairs from a prospective population-based birth cohort in Spain, in the Genetics, Early life enviroNmental Exposures and Infant Development in Andalusia (GENEIDA) project. Women were genotyped for MTHFR(677)C>T SNP by Q-PCR using TaqMan© probes. Relevant maternal and newborn information was obtained from structured questionnaires and medical records. Results showed that maternal MTHFR(677)C>T genotype was associated with newborn anthropometry. Genotypes CT or CT/TT showed statistically significant associations with increased or decreased risk of large-for-gestational-age (LGA) or small-for-gestational-age (SGA) based on weight and height, depending on the newborn’s sex, as well as with SGA in premature neonates. The relationships between this maternal genotype and anthropometry at birth remained despite an adequate maternal folate intake.

Prenatal Multivitamin Use and MTHFR Genotype Are Associated with Newborn Cord Blood DNA Methylation.

Background: Fetal development involves cellular differentiation and epigenetic changes—complex processes that are sensitive to environmental factors. Maternal nutrient levels during pregnancy affect development, and methylene tetrahydrofolate reductase (MTHFR) is important for processing the nutrient folate. Hypothesis: We hypothesize that supplement intake before pregnancy and maternal genotype are associated with DNA methylation in newborns. Methods: In the pregnancy cohort, Early Autism Risk Longitudinal Investigation (EARLI), health history, and genotype information was obtained (n = 249 families). Cord blood DNA methylation (n = 130) was measured using the Illumina HumanMethylation450k array and global DNA methylation levels were computed over 455,698 sites. Supplement use preconception and during pregnancy were surveyed at visits during pregnancy. We evaluated associations between maternal preconception supplement intake and global DNA methylation or DNA methylation density distributions of newborn cord blood, stratified by the presence of a variant maternal MTHFR C677T allele. Results: Maternal preconceptional multivitamin intake was associated with cord blood methylation, dependent on maternal MTHFR genotype (interaction term p = 0.013). For mothers without the MTHFR variant allele, multivitamin intake was associated with 0.96% (95% CI: 0.09, 1.83) higher global cord blood methylation (p = 0.04) and was also associated with the cumulative density distribution of methylation (p = 0.03). For mothers with at least one variant allele, multivitamin intake had a null −0.06% (95% CI: −0.45, 0.33) association with global cord blood DNA methylation, and was not associated with the cumulative density distribution (p = 0.37). Conclusions: We observed that cord blood DNA methylation was associated with maternal supplement exposure preconception and maternal genotype. Genetic context should be considered when assessing DNA methylation effects of modifiable risk factors around the time of pregnancy.

Study on Maternal SNPs of MTHFR Gene and HCY Level Related to Congenital Heart Diseases

The aim of this study is to evaluate the relationship between maternal single nucleotide polymorphisms (SNPs) of methylenetetrahydrofolate reductase (MTHFR) gene with plasma homocysteine (HCY) level and offspring congenital heart diseases (CHDs). 338 mothers with offspring CHDs as case group and 306 mothers of normal children as control group were recruited. Their pregnant histories were interviewed by questionnaire and the MTHFR rsl801133 and rsl801131 were genotyped. The case–control analysis was used to find out the relationship between maternal SNPs of MTHFR gene and offspring CHDs. And the plasma HCY concentration of the mothers of CHDs children was detected. This case–case study was intended to find out the relevance between maternal HCY level and SNPs of MTHFR gene. There were significant differences in the gender of children, occupation of mothers, family history with CHDs, history of abortion, history of adverse pregnancy, early pregnancy health, fetus during pregnancy, pesticide exposure and drug exposure in CHDs group and control group (P < 0.05). MTHFR rs1801133 was significantly associated with their offspring CHDs in mothers. The polymorphism of maternal MTHFR rs1801133 increased plasma HCY level, especially the homozygous mutation. Besides the environmental factors, our results suggested that the maternal MTHFR rs1801133 polymorphism might be a risk factor of their offspring CHDs, which may be due to the hyperhomocysteinemia by abnormal metabolism of HCY.

Analysis OF C677T polymorphism in methylene tetrahydrofolate reductase (MTHFR) gene as a risk factor for congenital talipes equino varus (CTEV)

BackgroundClubfoot is a common congenital foot deformity. Low folate status in mothers has been associated with CTEV. Folate metabolism might be affected by Methylene Tetrahydrofolate Reductase (MTHFR) gene polymorphism. The present study was aimed to investigate MTHFR C677T polymorphism and its association with CTEV. MethodsThis is a Case-mother-Dyad study with 30 pairs of cases and controls. Single Nucleotide Polymorphism (SNP) analysis of the MTHFR gene was done in this hospital-based study by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). ResultsIn this study, we observed less relative risk of CTEV in presence of C allele as compared to T allele in children, with Relative Risk- 0.6281 and likelihood ratio of 0.5714. While analysing the correlation of genotype variation in cases (CC = 8(26.66%) and CT = 22(73.33%)) with there biological mother (CC = 13(43.33%) and CT = 17(56.66%)), no significant correlation (p = 0.3110) was found between cases and their biological mother genotype. ConclusionAmong the enrolled cases, there was a significant association of increased CTEV risk with 677T variant allele of MTHFR gene. Also, maternal MTHFR genotype was not found to influence CTEV risk of offspring.

Prevalence of the methylenetetrahydrofolate reductase 677C>T polymorphism in the pregnant women of Yunnan Province, China.

Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene can result in a reduced ability to utilize folic acid. The MTHFR 677C>T polymorphism in particular has been linked to both birth defects and pregnancy-associated diseases. This study aimed to evaluate the prevalence of the MTHFR 677C>T mutation among pregnant women in Yunnan Province so as to collect baseline data that may be utilized to guide folic acid supplementation efforts and to support related disease prevention programs. We retrospectively reviewed 3387 pregnant women from Yunnan Province. The MTHFR 677C>T polymorphism was identified using polymerase chain reaction (PCR) and DNA sequencing. In total, 1350 (39.9%) subjects were homozygous for the C allele (CC), 1540 (45.4%) subjects were heterozygous (CT), and 497 (14.7%) subjects were homozygous for the T allele (TT). The MTHFR 677C>T polymorphism was found to be present within the studied population, with ∼60% of these patients being either heterozygous or homozygous for the mutant allele and with an overall T allele frequency of 0.37. The frequency of the T allele was significantly higher among pregnant women with complications relative to women with healthy pregnancies, particularly among women <30 years old. As such, the maternal MTHFR 677C>T polymorphism may be a genetic risk factor associated with pregnancy complications and may help identify pregnant women at a high risk of such complications.

Complex Nature of Neural Tube Defects: A Regional Experience

Objective: The underlying gene-environment interaction of fetal neural tube defects is affected by several factors including geography, ethnicity and time. Local features of fetal neural tube defects were described.Study Design: A prospective cohort study of 48 fetal neural tube defects in a single tertiary medical center at the northwestern region of Turkey (2013-2015) was done via ultrasound, magnetic resonance imaging (MRI), conventional karyotyping, maternal methylenetetrahydrofolate reductase c.677C&gt;T (rs1801133) single-nucleotide polymorphism and maternal serum levels of folic acid, vitamin B12 and zinc. For comparison of means, a Student’s T-Test was used.Results: The prevalence of neural tube defects was 11.4 per 10000 births (48/42000) in northwestern Turkey. The defects on the cranium (n=23; 47.9%) and spine (n=25; 52.1%) were ultrasonographically detected. MRI did not give additional benefit over the ultrasonography. The ratio of associated anomalies in neural tube defect group was 25%. Two fetal neural tube defects with Down syndrome were remarkable. The rate of homozygous methylenetetrahydrofolate reductase c.677C &gt; T SNPs among the mothers of neural tube defect fetuses (n=20) was 15%. Comparing with gestationally matched healthy pregnancies, although maternal BMIs and periconceptional folate intake of neural tube defect group were significantly different, maternal serum folic acid, vitamin B12 and zinc levels were similar.Conclusion: The northwestern region appeared to be a relatively low prevalence area of Turkey for fetal neural tube defects. Any association with maternal serum folic acid, vitamin B12 and zinc levels could not be shown in this region.

The association between maternal methylenetetrahydrofolate reductase C677T and A1298C polymorphism and birth defects and adverse pregnancy outcomes.

Published studies indicate the MTHFR C677T and A1298C polymorphisms are associated with abnormal homocysteine levels, which may cause various pregnancy complications and birth defects. However, the results obtained from different studies have been inconsistent. Therefore, this meta-analysis explores the association between MTHFR polymorphisms and birth defects and adverse pregnancy outcomes. The PubMed, ScienceDirect, Embase, and China Biology Medicine literature databases and ClinicalTrials were searched. Analyses of public bias, meta-regression, subgroups, and sensitivity were used to ensure the robustness of our results. MTHFR C677T was significantly associated with recurrent pregnancy loss in developing countries (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.20-1.50) but not in developed countries (OR, 0.87; 95% CI, 0.68-1.11). No significant relationship was found between MTHFR A1298C and recurrent pregnancy loss (OR, 1.04; 95% CI, 0.93-1.18). MTHFR C677T and A1298C were not associated with preeclampsia (OR, 1.06; 95% CI, 0.97-1.16 and OR, 1.16; 95% CI, 0.97-1.39, respectively), and C677T was not associated with placental abruption (OR, 1.03; 95% CI, 0.87-1.21), intrauterine growth retardation (OR, 1.02; 95% CI, 0.90-1.15), or congenital heart disease (OR, 1.05; 95% CI, 0.89-1.25). MTHFR C677T, but not A1298C, was associated with neural tube defects (OR, 1.24; 95% CI, 1.08-1.42) and Down syndrome (OR, 1.65; 95% CI, 1.39-1.95). CONCLUSION: Although MTHFR C677T and A1298C are significantly associated with some types of congenital defects and adverse pregnancy outcomes, the impact of these polymorphisms is moderate.

Impact of maternal methylenetetrahydrofolate reductase C677T polymorphism on intervillous and decidual pathology with pregnancy loss.

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and intervillous and decidual pathology in patients with pregnancy loss was investigated. We performed a cross-sectional study on 243 patients presenting with pregnancy loss for the degree of intervillous fibrin and thrombosis (IT), and decidual fibrin and thrombosis (DT) and determined their MTHFR C677T genotypes. Overall differences in age, body mass index (BMI), gravidity, parity, number of pregnancy losses and gestational period when the pathologic samples were obtained, also were determined. There were no significant differences in age, BMI, gravidity, parity, number of pregnancy losses and gestational period, relative to MTHFR C677T genotype (TT vs CT vs CC). There were significantly more T allele carriers and TT genotype patients among patients with severe IT (odds ratio [OR] 1.653, P = 0.033 and OR 2.246, P = 0.032, respectively) and those with severe IT and decidual thrombosis (OR 2.602, P = 0.012 and OR 3.375, P = 0.035, respectively). The CC genotype was protective against the four studied pathologic grades. To our knowledge, this is the first study showing that the MTHFR C677T TT genotype and T allele are associated with severe intervillous and decidual pathologies in patients with pregnancy loss. Differences in pathologic grades of MTHFR C677T TT genotype could support the hypothesis that further periconceptional treatment for pregnancy loss could be customized depending on single nucleotide polymorphisms.

Are Congenital Urinary Tract Abnormalities Linked to Maternal Methylenetetrahydrofolate Reductase Polymorphisms in Fetuses of Intentionally Terminated Pregnancies with Oligo- or Anhydramnios ?

ABSTRACTObjective: We aimed to evaluate fetuses of terminated pregnancies with oligo-or anhydramnios (OAH) to further investigate the association between maternal methylenetetrahydrofolate reductase (MTHFR) polymorphisms and fetal urinary tract malformations. Materials and Methods: This retrospective study included 16 pregnancies with OAH (with normal fetal karyotype) that were intentionally terminated before 22nd gestational week. Fetal autopsy was performed in all cases. We evaluated cases for presence of DNA methylation pathway-related gene polymorphisms. Results: We demonstrated that renal abnormalities and disorders exist in 75% of the cases. Pulmonary system anomalies and single umbilical artery were the most frequently observed associated abnormalities. Polymorphisms with known reduced MTHFR activity were found in 81.8% (9/11) of the cases.Association between urinary system abnormalities and polymorphisms with known reduced MTHFR activity was observed in 88.8% (8/9) of the cases. Conclusion: Physicians should keep in mind that polymorphisms with known reduced MTHFR activity may be associated with urinary tract abnormalities and OAH.

Low maternal folate concentrations and maternal MTHFR C677T polymorphism are associated with an increased risk for neural tube defects in offspring: a case-control study among Pakistani case and control mothers.

There is considerable evidence that periconceptional maternal folate deficiency and coding variants in maternal genes coding for critical enzymes in the folate pathway are associated with neural tube defects (NTDs) in offspring. In a case-control study we investigated C677T polymorphism in the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene in case and control mothers of Pakistani origin, and compared these with the respective maternal folate concentrations measured at the time of delivery. A case-control study was conducted among 109 case and 100 control mothers identified through the Holy Family Hospital Rawalpindi, Quaid-i-Azam University, Islamabad, Pakistan. Red blood cell (RBC) and serum folate concentrations and MTHFRC677T polymorphism were compared between case and control mothers. Mean RBC folate and serum folate concentrations were significantly lower in cases compared with control mothers (p<0.0001). Maternal MTHFR 677CT and 677TT genotypes were more common among cases compared with control mothers (CC vs TT p<0.0393 and CC/CT vs TT p<0.021). T-allele frequency was higher in cases compared with control mothers (C vs T p<0.017). Case mothers with 677CT or 677TT genotypes had significantly lower serum (p<0.0001) and RBC folate concentrations (p<0.0001) compared with control mothers. The present study provides further evidence that maternal folate deficiency and MTHFRC677T polymorphism might be associated with an increased risk for NTDs in offspring. Our results are limited by the fact that maternal folate concentrations were not obtained during the periconceptional period, but at delivery. Further analyses, including maternal folate levels during the periconceptional period, are warranted.

Systematic review and meta-analysis of the associations between maternal methylenetetrahydrofolate reductase polymorphisms and preterm delivery.

To date, reported associations between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and preterm delivery are conflicting. The present meta-analysis summarized the existing evidence and evaluated these associations. Eligible studies were retrieved from Medline (PubMed), EMBASE, the Chinese Biomedical Literature Database and the Cochrane Library. We calculated pooled odds ratios (ORs) and 95% confidence interval (CIs) within five genetic models using either random-effects or fixed-effects models dependent on study heterogeneity. Potential publication bias was assessed using a Begg's test. Sensitivity analysis was performed to evaluate the stability of the results. Thirteen studies involving 4816 mothers who experienced preterm delivery and 34 506 normal controls were finally included. Significant associations between MTHFR C677T polymorphism and the risk of preterm delivery were detected overall (ORT/C = 1.34, 95% CI 1.12-1.61; ORTT/CC = 1.60, 95% CI 1.21-2.11; ORCT/CC = 1.33, 95% CI 1.07-1.65; ORTT/(CC + CT) = 1.41, 95% CI 1.11-1.78; OR(TT + CT)/CC = 1.36, 95% CI 1.11-1.66) and in an Asian population (ORT/C = 1.80, 95% CI 1.24-2.62; ORTT/CC = 2.13, 95% CI 1.27-3.57; ORCT/CC = 1.93, 95% CI 1.37-2.71; OR(TT + CT)/CC = 2.03, 95% CI 1.49-2.77). Negative associations of the A1298C polymorphism were only observed among Asian pregnant women (ORC/A = 0.66, 95% CI 0.50-0.88; ORCC/AA = 0.10, 95% CI 0.02-0.53; ORCC/(AA + AC) = 0.11, 95% CI 0.02-0.57; OR(CC + AC)/AA = 0.68, 95% CI 0.49-0.94). MTHFR 677 T may play a significant role in regard to the risk of preterm delivery, especially in the Asian population.

Genetic polymorphism of MTHFR C677T with preterm birth and low birth weight susceptibility: a meta-analysis.

This study aimed at clarifying the association of maternal and neonatal methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms with preterm birth (PTB) and low birth weight (LBW) susceptibility, respectively. A systematic search of Embase, Medline, China Biological Medicine Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang Database was performed before June, 2016. The frequencies of maternal and neonatal MTHFR C677T genotypes in the cases and controls and other information were extracted by two independent investigators. Odds ratios (ORs) with 95% confidence intervals (CIs) were adopted to estimate the relationships between MTHFR C677T polymorphisms and PTB as well as LBW by random or fixed effect models. Twenty-five studies from 20 articles concerning maternal and neonatal MTHFR C677T gene polymorphism with PTB and LBW were included in this study. Maternal MTHFR C677T polymorphism was associated with PTB risk under allele contrast (T vs. C, OR = 1.36, 95% CI 1.02-1.81), homozygote (TT vs. CC, OR = 1.70, 95% CI 1.07-2.68), and recessive (TT vs. CT + CC, OR = 1.49, 95% CI 1.00-2.22) model, but not dominant or heterozygote model. Maternal MTHFR C677T polymorphism was also associated with LBW risk under allele contrast (OR = 1.69, 95% CI 1.25-2.28), homozygote (OR = 2.26, 95% CI 1.44-3.54), dominant (OR = 1.71, 95% CI 1.19-2.47), recessive (OR = 1.79, 95% CI 1.42-2.26) model, but not heterozygote model. No associations between neonatal MTHFR C677T polymorphism and PTB or LBW were found under all genetic models. Identification of maternal MTHFR C677T mutation may play a key role for primary prevention of PTB as well as LBW and screening pregnant women of high risk in developing countries.