Methylenetetrahydrofolate Reductase Gene Polymorphisms Research Articles

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.

MTHFR Gene C677T Polymorphism (rs1801133) and Susceptibility to Colorectal Polyps in an Azerbaijani Population.

Understanding the relationships between the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, colorectal polyps, and CRC risk can aid in advancing personalized medicine approaches in CRC prevention. The aim of the current study is to identify the association of C677T polymorphism of the MTHFR gene with the risk of colorectal polyps in the Azerbaijani population. This study included 125 patients with colon polyps and 155 healthy individuals as a control group. DNA was extracted from venous blood samples obtained from patients and healthy individuals, and the results were analyzed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis. Wild-type, heterozygote, and homozygous mutant were revealed within 69 (55.2%), 49 (39.2%), and 7 (5.6%) patients and within 100 (64.5%), 45 (29%), and 10 (6.5%) healthy controls, respectively. However, no significant statistical associations were observed between CT and TT genotypes, dominant (CC vs. CT + TT) and recessive (CC + CT vs. TT) models, and the mutant T allele and disease risk. There were also no significant differences between patients and controls regarding age, sex, smoking and alcohol use. Our research did not reveal any significant association between the MTHFR C677T polymorphism and susceptibility to colorectal polyps in the Azerbaijan population.

A Genetic Association Study of MTHFR C677T Polymorphism with Risk of Metabolic Syndrome: A Systematic Review and Meta-Analysis

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that plays a crucial role as a methyl-group donor in demethylation of homocysteine. The aim of this systematic review and meta-analysis was to study the relationship between MTHFR gene polymorphism and metabolic syndrome (MS). We used search engines and databases such as Science Direct, Google Scholar, Embase, Cochrane Library, and PubMed to identify eligible studies up to 2018. The articles were studied based on keywords including MTHFR, mutation, variant, and polymorphism in combination with MS. Data was analyzed using Comprehensive Meta-Analysis version 2.2.064 software. After extracting the data from seven articles, the total number of subjects was 1280 in the patient group and 1374 in the control group. The odds ratio was estimated to be 1.078 for the allele model of T vs. C (95% confidence interval [CI]: 1.626-0.715), 1.157 for the allele model of CC vs. CT (95% CI: 0.829-1.615), 1.020 for the allele model of CT + TT vs. CC (95% CI: 1.611-0.646) and 0.799 for the allele model of TT vs. CC + CT (95% CI: 1.185-0.539). As well, the results showed no statistically significant correlation between polymorphism genotypes of the MTHFR gene and MS (P<0.05). In general, this study showed that the presence of C677T polymorphism in the MTHFR gene has no effect on the incidence of MS. [GMJ.2019;8:e1472]

Association between COVID-19 Infection or Vaccination Outcomes and Methylenetetrahydrofolate Reductase Gene Polymorphism: A Systematic Review of the Literature.

Thrombosis is a detrimental sequala of COVID-19 infection; thus, prophylactic anti-coagulant therapy has been deemed mandatory in treatment unless serious contraindications are present. Susceptibility to thromboembolic events in COVID-19, or following COVID-19 vaccination, is likely attributable to an interplay of factors, including a patient's baseline clinical status and comorbidities, alongside genetic risk factors. In Europe, 8-20% of the population are homozygous for the MTHFR (methylene tetrahydrofolate reductase) variant, which compromises folate metabolism and elevates homocysteine levels. While heightened homocysteine levels are considered a risk factor for thromboembolic events, the precise clinical significance remains a contentious issue. However, recent research suggests elevated homocysteine levels may predict the course and severity of COVID-19 infection. Given the lack of reliable biomarkers predictive of COVID-19 thrombotic risk existing in practice, and the accessibility of MTHFR screening, we established two main outcomes for this study: (1) to determine the association between hereditary MTHFR mutations and COVID-19 severity and thromboembolic events and (2) to determine the link between MTHFR variants and adverse thrombotic events following COVID-19 vaccination. The review was conducted in accordance with PRISMA guidelines. Medline, Scopus, and Web of Science databases were searched from pandemic inception (11 March 2020) to 30 October 2023. Eligibility criteria were applied, and data extraction performed. From 63 citations identified, a total of 14 articles met the full inclusion criteria (8 of which were cross-sectional or observational studies, and 6 were case studies or reports). Among the eight observational and cross-sectional studies evaluating the relationship between MTHFR variants (C667T; A1298C) and thromboembolic events in COVID-19 infection, four studies established a connection (n = 2200), while the remaining four studies failed to demonstrate any significant association (n = 38). This systematic review demonstrated a possible association between the MTHFR gene variants and COVID-19 severity, thromboembolic events, and adverse events following vaccination. However, the paucity of robust data precluded any firm conclusions being drawn. Further prospective trials are required to determine the connection between the MTHFR gene variant and COVID-19 infection and vaccination outcomes.

Methylenetetrahydrofolate Reductase Gene Polymorphism as a Risk Factor for Coronary Artery Disease

Methylenetetrahydrofolate Reductase Gene Polymorphism as a Risk Factor for Coronary Artery Disease

MTHFR gene polymorphisms and susceptibility to myocardial infarction: Evidence from meta-analysis and trial sequential analysis

BackgroundThis meta-analysis aimed to provide a comprehensive assessment of the association between Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, specifically C677T and A1298C, and the susceptibility to myocardial infarction (MI). MethodsA systematic literature search was conducted in MEDLINE, Web of Science, and Scopus until April 2023 to identify studies investigating the relationship between MTHFR gene polymorphisms (C677T and A1298C) and the risk of MI. ResultsThe analysis included 66 studies involving 16,860 cases and 20,403 controls for the C677T polymorphism and 18 studies comprising 3162 cases and 3632 controls for the A1298C polymorphism. Significant associations were observed between the C677T polymorphism and MI risk in various genetic models: dominant (OR = 1.16, 95 % CI = 1.06–1.28, P = 0.008), recessive (OR = 1.20, 95 % CI = 1.12–1.28, P < 0.001), allelic (OR = 1.13, 95 % CI = 1.06–1.21, P < 0.001), TT vs. CC (OR = 1.19, 95 % CI = 1.05–1.36, P < 0.001), and CT vs. CC (OR = 1.11, 95 % CI = 1.02–1.21, P = 0.01). Furthermore, an overall analysis indicated a marginally significant association between the A1298C polymorphism and MI risk in the recessive model (OR = 1.27, 95 % CI = 1.06–1.51, P = 0.008), allelic model (OR = 1.18, 95 % CI = 1.01–1.39, P = 0.03), and CC vs. AA model (OR = 1.22, 95 % CI = 1.01–1.47, P = 0.04). Meta-regression analysis revealed that none of the potential factors contributed to the observed heterogeneity. ConclusionsThis meta-analysis revealed an association between MTHFR gene C677T and A1298C polymorphisms and the risk of MI.

Association of epistatic effects of MTHFR, ACE, APOB, and APOE gene polymorphisms with the risk of myocardial infarction and unstable angina in Egyptian patients

Despite remarkable discoveries in the genetic susceptibility of coronary artery disease (CAD), a large part of heritability awaits identification. Epistasis or gene‐gene interaction has a profound influence on CAD and might contribute to its missed genetic variability; however, this impact was largely unexplored. Here, we appraised the associations of gene-gene interactions and haplotypes of five polymorphisms, namely methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, angiotensin converting enzyme (ACE) insertion/deletion (I/D), apolipoprotein B (APOB) R3500Q, and apolipoprotein E (APOE) ε4 with the risk of myocardial infarction (MI) and unstable angina (UA). Gene-environment interactions with traditional risk factors and clinical data were also scrutinized. This study recruited 100 MI, 50 UA patients, and 100 apparently healthy controls. Logistic regression models were employed in association analyses. We remarked that the single locus effect of individual polymorphisms was relatively weak; however, a magnified effect of their combination via gene-gene interaction may predict MI risk after adjustment for multiple comparisons. Only MTHFR C677T, ACE I/D, and APOB R5300Q were associated with the risk of UA, and the ACE I/D-R3500Q interaction posed a decreased UA risk. APOB R3500Q was in strong linkage disequilibrium with MTHFR C677T, ACE I/D, and APE ε4 polymorphisms. The TCDGε3, CADGε4, and TADGε4-C677T-A1298C-ACE I/D-R3500Q-APOE haplotypes were associated with escalating MI risk, while the CDG or CIG-C677T-ACE I/D-R3500Q haplotype was highly protective against UA risk compared to controls. Interestingly, the CADGε4 and CAIGε3 haplotypes were strongly associated with the presence of diabetes and hypertension, respectively in MI patients; both haplotypes stratified patients according to the ECHO results. In UA, the CDG haplotype was negatively associated with the presence of diabetes or dilated heart. Conclusively, our results advocate that a stronger combined effect of polymorphisms in MTHFR, ACE, APOB, and APOE genes via gene-gene and gene-environment interactions might help in risk stratification of MI and UA patients.

Association Between MTHFR Gene Polymorphism (A1298c) C&gt;A and Sensitivity to Cervical Cancer: A Meta-Analysis

We have investigated the association between methylenetetrahydrofolate reductase A1298C polymorphism and cervical cancer. A comprehensive search was conducted in Wanfang, China HowNet and PubMed databases to retrieve Chinese and English literature from the construction of the database to December 2019. Stata software was utilized to conduct the analysis of the five genetic models, while the odds ratio and 95% confidence interval were employed to assess the correlation. 12 pertinent publications were included with 3839 subjects (1546 patients and 2293 healthy control). There were no significant associations between A1298C and cervical cancer risk under recessive model, dominant model, allele model, co-dominant model. In the sub-analysis by ethnic groups, a significant association between A1298C and cervical cancer risk under recessive model in Asia. It is suggested a potential association between methylenetetrahydrofolate reductase gene polymorphism A1298C and an elevated susceptibility to cervical cancer in the Asian population, specifically under the recessive model.

Relationship between MTHFR gene polymorphism and risk of thrombosis in postoperative patients with colorectal cancer.

An association between the methylenetetrahydrofolate reductase (MTHFR) C667T genotype and the risk of colorectal cancer, as well as a link between MTHFR gene polymorphism and thrombosis, have been revealed. However, the connection between MTHFR gene polymorphism and the risk of thrombosis in patients with colorectal cancer has remained to be fully elucidated. The present study investigated the link between MTHFR gene polymorphism and basic clinical data, postoperative D-dimer (DDi), postoperative thromboelastogram and postoperative thrombosis in 591 patients who underwent surgery for colorectal cancer. Postoperative DDi, thromboelastogram and postoperative thrombosis were not significantly different among patients with colorectal cancer and different MTHFR genotypes. While the results were 'negative', the present study may help physicians understand that it is not necessary to detect MTHFR polymorphism for therapeutic purposes. Regarding the danger of venous thrombosis, more focus should be placed on the standardized procedural enforcement system for deep vein thrombosis prevention for patients undergoing pelvic and abdominal surgery.

Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic.

Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.

Association of MTHFR polymorphism, folic acid and vitamin B12 with serum homocysteine levels in pregnant women.

Homocysteine is known to be associated with adverse vascular and metabolic effects, as well as pregnancy complications. Its serum levels are influenced by the function of the enzyme methylenetetrahydrofolate reductase (MTHFR) and the dietary intake of folic acid, vitamin B12, and methionine. In this cross-sectional study, we investigated the association of genetic polymorphisms of the MTHFR gene with vitamin status in pregnant women during mandatory folic acid supplementation. The study included 102 pregnant women between 24 and 28 weeks of gestation who were attending regular outpatient examinations at the maternity clinic. Homocysteine, folic acid, vitamin B12 levels, and MTHFR gene polymorphisms (C677T and A1298C) were analyzed. Significant associations were found between vitamin B12 and folic acid levels with homocysteine (P < 0.001), with lower serum levels of these vitamins being associated with higher homocysteine levels. Surprisingly, there was no significant association between MTHFR genetic polymorphisms and serum homocysteine levels, likely attributed to the supplementation of folic acid and vitamin B12 in vitamin supplements for pregnant women, which counteracts the effect of the mutation. Remarkably, a high prevalence of MTHFR gene mutations was found, with the C677T polymorphism present in 56.9% and the A1298C polymorphism in 87.2% of pregnant women. These findings emphasize the importance of adequate folic acid and vitamin B12 intake during pregnancy to regulate homocysteine levels. Although the MTHFR gene mutations were highly prevalent, their influence on homocysteine levels in this population appears to be mitigated by vitamin supplementation. Further research is warranted to explore the impact of these mutations on other aspects of pregnancy outcomes. The trial is registrated at Clinicaltrail.gov (NCT04952324).

ALDH2 rs671 and MTHFR rs1801133 polymorphisms are risk factors for arteriosclerosis in multiple arteries

BackgroundArteriosclerosis in multiple arteries has long been associated with heightened cardiovascular risk. Acetaldehyde dehydrogenase 2 (ALDH2) and methylenetetrahydrofolate reductase (MTHFR) play an important role in the pathogenesis of arteriosclerosis by participating in the oxidation and reduction reactions in vascular endothelial cells. The purpose was to investigate the relationship of ALDH2 and MTHFR gene polymorphisms with arteriosclerosis in multiple arteries.Methods410 patients with arteriosclerosis in single artery and 472 patients with arteriosclerosis in multiple arteries were included. The relationship between ALDH2 rs671 and MTHFR rs1801133 polymorphisms and arteriosclerosis in single artery and arteriosclerosis in multiple arteries was analyzed.ResultsThe proportion of ALDH2 rs671 A allele (35.6% vs. 30.9%, P = 0.038) and MTHFR rs1801133 T allele (32.6% vs. 27.1%, P = 0.012) in patients with arteriosclerosis in multiple arteries was significantly higher than that in arteriosclerosis in single artery, respectively. The proportion of history of alcohol consumption in patients with ALDH2 rs671 G/G genotype was higher than those in ALDH2 rs671 G/A genotype and A/A genotype (P < 0.001). The results of logistic regression analysis indicated that ALDH2 rs671 A/A genotype (A/A vs. G/G: OR 1.996, 95% CI: 1.258–3.166, P = 0.003) and MTHFR rs1801133 T/T genotype (T/T vs. C/C: OR 1.943, 95% CI: 1.179–3.203, P = 0.009) may be independent risk factors for arteriosclerosis in multiple arteries (adjusted for age, sex, smoking, drinking, hypertension, and diabetes).ConclusionsALDH2 rs671 A/A and MTHFR rs1801133 T/T genotypes may be independent risk factors for arteriosclerosis in multiple arteries.

Associations of serum 25-hydroxyvitamin D with serum folate, cobalanin, and homocysteine concentrations and methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in healthy adults.

The aim of this study was to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with various demographic, anthropometric, and genetic characteristics and biochemical parameters in healthy Greek adults. Demographic (age and sex), anthropometric (body mass index/BMI), and genetic (MTHFR gene polymorphisms) characteristics and biochemical parameters (serum folate, cobalamin/Cbl, and total homocysteine/tHcy concentrations), which had been recorded and measured, among others, in the framework of periodic medical examination (military personnel) or check-up (non-military personnel) of 383 healthy Greek adults (199 men and 184 women) were analyzed. Serum 25(OH)D, tHcy, folate, and Cbl levels were determined using immunoassay methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. Serum 25(OH)D concentrations were correlated with Cbl levels and MTHFR C677T gene polymorphism, while they had a reverse correlation with serum tHcy levels, age, and BMI. There was no significant correlation between serum 25(OH)D concentrations and sex, serum folate levels, and smoking status. Individuals with the 677TT genotype had statistically significantly lower serum 25(OH)D levels than those with the 677CC or 677CT genotype, while individuals with the 1298CC genotype had statistically significantly higher serum 25(OH)D levels than those with 1298AA or 1298AC genotype. Moreover, the reverse correlation between the serum 25(OH)D and tHcy levels was statistically significant in all six MTHFR genotypes. Serum 25(OH)D levels are associated with age, BMI, serum tHcy, and Cbl levels and MTHFR C677T gene polymorphism. The most significant finding of our study is the observed reverse correlation of serum 25(OH)D levels with serum tHcy levels. Considering that vitamin D deficiency and hyperhomocysteinemia (HHcy) are associated with an increased risk for cardiovascular diseases (CVDs), we suggest that individuals with high serum tHcy levels should be further investigated for, inter alia, their serum 25(OH)D levels.

Association of C677T and A1298C genetic polymorphisms in MTHFR gene with fetal growth restriction, small for gestational age and low birth weight: A meta-analysis

Impaired fetal growth has a wide range of short-term and long-term effects on physical and mental health. Fetal Growth Restriction (FGR), Small for Gestational Age (SGA) and Low Birth Weight (LBW) are three diagnoses of impaired fetal growth/size, but differences between them are not fully understood. This meta-analysis aimed to investigate the association of two genetic variants C677T and A1298C in methylenetetrahydrofolate reductase (MTHFR) gene with the risk of impaired fetal growth and then confirm this association with specific diagnosis. According to PRISMA protocols, 24 articles were included after searching the following databases: PubMed, Google Scholar, Science Direct, Web of Science, Cochrane Library and Cyber-Lenics. Meta-analysis was conducted in dominant, recessive, and allelic models of inheritance. According to our data, MTHFR C677T is associated with higher risk of impaired fetal growth and especially with FGR susceptibility (OR = 1.93, 95% CI 1.27–2.95, P = 0.002). On the other hand, MTHFR A1298C can be suggested as a risk factor of SGA (OR = 1.61, 95% CI 1.16–2.24, P = 0.005). However, it has no significant association with FGR or LBW. Our findings help to better understand MTHFR impact on fetal growth and distinguish FGR and SGA as separated cases of fetal growth abnormality.

Nutritional deficiency and MTHFR gene polymorphism in obstetrics

: This study was carried out to determine the association of folic acid deficiency, vitamin B12 deficiency, hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with obstetrical events linked to folic acid deficiency like neural tube defects (NTD); unexplained abruption placentae (AP), recurrent pregnancy loss (RPL) and preterm labour(PTL).: In the present study 87 pregnant females with past or present history of either neural tube defect (NTD), abruptio placentae, recurrent pregnancy loss (RPL) or preterm labour and 100 pregnant females without any such history were enrolled. Serum levels of folic acid, vitamin B12 and homocysteine in these females were estimated using chemiluminescence and Polyacrylamide gel electrophoresis (PAGE) was used to detect MTHFR gene polymorphism.: No significant association was observed between serum folic acid levels and NTD (p = 0.495), RPL (p = 0.832) or preterm labour (p = 0.724). However, folic acid deficiency had significant association with the occurrence of abruptio placenta (p = 0.001). Serum vit B12 deficiency was found to be a significant risk factor only in patients with RPL. Increased homocysteine revealed significant association with RPL (p= 0.024), abruption placentae (p=0.002) and preterm labour (0.015). No polymorphism in MTHFR gene could be revealed in the above pregnancy complications.: In the present study, deficiency of folic acid was uncommon probably due to its routine supplementation throughout the first trimester. However, preconceptional folic acid supplementation still needs to be emphasized to build up adequate folic acid levels required during embryogenesis. The relationship between vit B12 and RPL needs studies on larger number to establish the association before supplementation is suggested. MTHFR677 gene polymorphism may have remained undetected due to small sample size.

Association of MTHFR C667T Polymorphism, Homocysteine, and B Vitamins with Senile Cataract.

Senile cataract has become the leading cause of visual impairment and even blindness in the world, but there are few reports on its relationship with methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. This study is aimed to investigate the correlation between MTHFR gene polymorphisms or its enzyme metabolites and senile cataract. From January 2019 to June 2020, 663 patients with senile cataract at the Mianyang Central Hospital were enrolled as the observation group, and 646 healthy subjects were randomly selected as the control group. MTHFR gene polymorphisms (i.e., CC, CT, or TT genotypes) and serum homocysteine (HCY), folic acid (FOL), vitamin B12 (VitB12), and vitamin B6 (VitB6) levels were detected. The mutation rate of MTHFR C677T and HCY levels in the observation group were significantly higher than those in the control group, whereas FOL, VitB12, and VitB6 were significantly lower. With an increase in the MTHFR C677T mutation, HCY showed an upward trend, whereas FOL and VitB12 showed a decreasing trend in both the observation and control groups. Multiple logistic regression analysis showed that HCY and FOL were associated with senile cataract and MTHFR mutations; VitB12 was only associated with senile cataract. Compared to that with the CC genotype, CT and TT genotypes were associated with an increased senile cataract risk. Monitoring MTHFR gene polymorphisms and changes in serum HCY, FOL, and VitB12 levels could provide references in predicting senile cataract.

Dual effect of methylene-tetrahydrofolate reductase and angiotensin-converting enzyme gene polymorphisms on the risk of acute ischemic stroke

Dual effect of methylene-tetrahydrofolate reductase and angiotensin-converting enzyme gene polymorphisms on the risk of acute ischemic stroke

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.

Methylenetetrahydrofolate reductaseC677T and A1298Cpolymorphisms and gastric cancer susceptibility: an updated meta-analysis.

Widely regarded as one of the most prevalent malignancies worldwide, gastric cancer(GC) is a common clinical condition of the digestive system.Reviewing14 meta-analyses that evaluated the association between Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and GC risk, we observed inconsistent results, and the credibility of the significant correlation between the statistical results was ignored. With the aim of further exploring the association between MTHFRC677Tand CA1298Cand the risk of GC, we searched electronic databases, pooling 43 relevant studies and calculating odds ratios (ORs)and corresponding 95% confidence intervals (CIs)for each of the five genetic models. Subgroup and regression analyses were performed to look for sources of heterogeneity and publication bias was assessed by funnel plots.To assess the plausibility of statistically significant associations, we used the FPRP test and the Venice criteria. Overall data analysis showed that MTHFRC677Tpolymorphismwas significantly associated with GC risk, especially in Asians, while MTHFRCA1298Cpolymorphism was not associatedwith GC risk. However, insubgroup analysisby hospital-based controls, we found that MTHFRCA1298Cmight be a protective factor for GC. After credibility assessment, the statistical association between MTHFRC677Tand GCsusceptibility study was classified as "less credible positive result", while the result of MTHFRCA1298Cwas considered unreliable.In summary, this study strongly suggests that MTHFR, C677Tand CA1298Cpolymorphisms are not significantly associated with the GC risk.

Associations of MTHFR gene polymorphism with lipid metabolism and risk of cerebral infarction in the Northwest Han Chinese population.

Genetic variation in the methylenetetrahydrofolate reductase (MTHFR) gene may contribute to the development of cerebral infarction (CI); however, results have been inconsistent across studies with different populations, including studies of the Chinese population. The aim of this study was to analyze the effect of MTHFR gene polymorphism on serum lipid and homocysteine levels among patients with CI in the Northwest Chinese Han population. A total of 521 CI patients and 524 non-CI controls were enrolled in the study. Polymerase chain reaction and hybridization were utilized to identify MTHFR gene polymorphisms. Multivariate logistic regression analysis was used to assess the associations of MTHFR gene polymorphism with risk of CI. Frequencies of the TT genotype and the T allele were markedly higher among CI patients than among controls. After stratifying our data by sex and age, we determined that these differences in frequency of the TT genotype and the T allele were statistically significant among participants of two different age brackets and among men, but not among women (i.e., there were no statistically significant differences between female patients and female controls). CI patients and control participants with the CT or TT genotype had significantly higher homocysteine (Hcy) levels than those with the CC genotype. Among CI patients, CT/TT carriers showed significantly lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) levels as compared with CC carriers, but there was no significant difference for control participants. Multivariable logistic regression analysis showed that drinking; smoking; diabetes mellitus; levels of Hcy, direct bilirubin (DB), indirect bilirubin (IB), ApoA-I, and total protein (TP); and TT genotype were significant independent risk factors for CI. The results suggested that the TT genotype of the MTHFR C677T gene polymorphism, which is associated with hyperhomocysteinemia (HHcy), might be of great clinical significance in the identification of new biomarkers for CI and in the development of individualized preventive and therapeutic strategies.