MTHFR C677T Gene Polymorphism Research Articles

Deciphering the folate puzzle: Unraveling the impact of genetic variations and metabolites on cancer risk.

The C677T polymorphism in the MTHFR gene and its role in folate metabolism, impacting serum folate metabolites like THF and 5-MTHF, is a critical but underexplored area in cancer research. This nested case-control study utilized data from CHHRS, involving 87,492 hypertensive adults without prior cancer. During a median of 2.02 years, we identified 1332 cancer cases and matched controls based on age, sex, and residency. Serum levels of folate, THF, and 5-MTHF were measured, and the MTHFR C677T gene polymorphism was considered. Statistical analyses included restricted cubic spline regression and conditional logistic regression models. Serum THF levels were inversely associated with overall cancer risk (ORper SD = 0.90, 95% CI = 0.82-0.99), while 5-MTHF levels showed a negative association in the general cohort (ORQ3 vs. Q1 = 0.76, 95% CI = 0.60-0.96; ORQ4 vs. Q1 = 0.75, 95% CI = 0.58-0.98) and in individuals with MTHFR C677T (CC + CT) polymorphism (ORper SD = 0.87, 95% CI = 0.77-0.99; ORQ4 VS. Q1 = 0.79, 95% CI = 0.61-0.98), but a positive association in the MTHFR C677T (TT) subgroup (ORper SD = 1.89, 95% CI = 1.02-3.72; ORQ4 VS. Q1 = 2.17, 95% CI = 1.06-8.21). The impact of folate, THF, and 5-MTHF on cancer risk varied significantly across different cancer types and MTHFR C677T genotypes. This study provides novel insights into the variable effects of folate and its metabolites on cancer risk, influenced by genetic factors like the MTHFR C677T polymorphism and cancer type.

Association of MTHFR (C677T, A1298C) and MTRR A66G polymorphisms with fatty acids profile and risk of neural tube defects.

This study aims to determine if 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms were associated with fatty acid (FA) levels in mothers of fetuses with neural tube defects (NTDs) and whether these associations were modified by environmental factors. Plasma FA composition was assessed using capillary gas chromatography. Concentrations of studied FA were compared between 42 mothers of NTDs fetuses and 30 controls as a function of each polymorphism by the Kruskal-Wallis nonparametric test. In MTHFR gene C677T polymorphism, cases with (CT + TT) genotype had lower monounsaturated FAs (MUFA) and omega-3 polyunsaturated FA (n-3 PUFA) levels, but higher omega-6 polyunsaturated FAs (n-6 PUFA) and omega-6 polyunsaturated FAs: omega-3 polyunsaturated FAs (n-6:n-3) ratio levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype had lower MUFA levels, but higher PUFA and n-6 PUFA levels. Controls with (AG + GG) genotype had lower n-6 PUFA levels. In MTHFR gene C677T polymorphism, cases with smoking spouses and (CT + TT) genotype had lower MUFA and n-3 PUFA levels, but higher PUFA, n-6 PUFA, and n-6:n-3 ratio levels. Cases with (CT + TT) genotype and who used sauna during pregnancy had lower n-3 PUFA levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype and who used sauna during pregnancy had higher PUFA and n-6 PUFA levels. Further research is required to clarify the association of FA metabolism and (MTHFR, MTRR) polymorphisms with NTDs.

MTHFRC 677T Gene Polymorphism and Homocysteine in North China Patients with Varicocele

To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, homocysteine, and male infertility with varicocele in North China. One Hundred infertile males with varicocele (VC; grade II-III, VC group) and 100 healthy males with normal semen parameters and no varicocele (NC group) were recruited for PCR microarray, blood and semen testing. Compared with the CC genotype in the NC group, the TT genotype in the NC group and the CC genotype in the VC group showed no significant changes in sperm motility (P=0.191; P=0.130), sperm density (P=0.591, P=0.643), plasma homocysteine level (P=0.511; P=0.677), and seminal plasma MDA (P=0.752; P=0.451). In contrast, VC patients with the TT genotype had higher plasma homocysteine level and seminal plasma MDA levels (P <0.001), lower partial pressure of oxygen in seminal pulse (PO2; P <0.001) and poorer sperm quality (P <0.001), as compared with the CC genotype. This suggests that MTHFR C677C>T may not be a risk factor for male Varicocele in North China. However, this may affect the oxidative stress associated with homocysteine expression, which in turn affects semen parameters in VC patients. Larger studies are needed to validate our findings.

Association between MTHFR C677T Gene Polymorphisms and the Efficacy of Vitamin Therapy in lowering Homocysteine Levels among Stroke Patients with Hyperhomocysteinemia.

The impact of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation on the relationship between plasma homocysteine (Hcy) levels and stroke has been extensively studied and documented in previous study. However, it remains unclear whether the MTHFR C677T mutation can affect the response to Hcy lowering treatment in stroke patients with hyperhomocysteinemia (HHcy). Understanding the impact of genetic factors on treatment response can help optimize personalized treatment strategies for stroke patients with HHcy. We aimed to investigate the potential association between the MTHFR C677T gene polymorphisms and the effectiveness of Hcy lowering treatment using vitamin therapy in stroke patients with HHcy. The MTHFR C677T genotype polymorphisms were identified using polymerase chain reaction-restriction fragment length polymorphism, and the distribution of three genotypes in the MTHFR C677T gene locus was compared. The treatment effects of Hcy lowering agents were compared among patients with different genotypes. Among the 320 stroke patients enrolled in the study, 258 (80.6%) were diagnosed with HHcy. Of these, 162 patients (Effective Group) responded well to the clinical Hcy lowering treatment, while 96 patients (Invalid Group) failed to achieve sufficient response even after taking combination supplements of folic acid, Vitamin B6, and methylcobalamin for one month. Significant differences were observed in terms of age (p < 0.001), hypertension (p = 0.034), dyslipidemia (p = 0.022), hyperuricemia (p = 0.013) and genotype distribution of MTHFR C677T gene polymorphism (p < 0.001) between the Invalid group and the Effective group. The multivariate regression analysis revealed that the T allele (odd rations [OR], 1.327; 95% confidence interval [CI], 1.114-1.580; p = 0.0015) was independently associated with an insufficient Hcy lowering treatment effect. Additionally, the TT genotype was independently associated with insufficient response in both the codominant model (OR, 1.645; 95% CI, 1.093-2.476; p = 0.017) and the recessive model (TT versus CC + CT; OR, 1.529; 95% CI, 1.145-2.042; p = 0.004). However, no relationship was observed between CT + TT genotypes and poor treatment effect in the dominate model. Our findings suggested that the TT genotype and T allele of MTHFR C677T polymorphism were independently associated with an insufficient Hcy lowering treatment effect in stroke patients with HHcy.

Penetrance of Arsenic Modulates Gene Expression of Epithelial Mesenchymal Transition Marker SOX4, EpCAM and CK19 Genes Through MTHFR C677T Polymorphism Regulation in Circulating Tumour Cells Isolated from Breast Cancer Patients

Arsenic is a common environmental agent that modulates various kind of disease including cancer. However, the exact role of arsenic induce in breast cancer development remains unknown in circulating tumor cells (CTCs). Therefore, present study has been designed with the aims to elucidate the impact of arsenic exposure i.e 24, 48, and 72 hours on epithelial-mesenchymal transition (EMT) markers such as Sox4, EpCAM, and CK19. RT-PCR analysis was carried out for the characterization of EMT with specific primers on agarose gel electrophoresis. DNA copy number variation (DNACNVs) was evaluated to assess genetic susceptibility and MTHFR C677T gene polymorphism was examined to determine the “risk factor” in CTCs isolated from breast cancer patients. Interestingly, findings reveal the differential gene expression and a pattern of down regulation (under expression) were observed during 24 and 48 hours of exposure, followed by up regulation at 72 hours. Genetic heterogeneity of the MTHFR C→T allele was detected only at 48 hours, suggesting that arsenic increase “risk” for developing breast cancer by modulating EMT marker either alone or synergistically with MTHFR in CTCs.

The effects of folinic acid and l-methylfolate supplementation on serum total homocysteine levels in healthy adults

Hyperhomocysteinemia is recognized as a risk factor for several diseases and conditions. The aim of this study was to investigate and compare the efficacy of two total homocysteine (tHcy)-lowering treatments including folinic acid or l-methylfolate in healthy Greek adults. Two hundred and seventy-two healthy Greek adults (143 men, 129 women; mean age±SD: 43.0±15.3 years), with serum tHcy levels ≥10μmol/L received randomized folinic acid ("Folinic acid Group") or l-methylfolate ("l-methylfolate Group") orally for three months. All subjects with serum cobalamin (Cbl) levels <300pg/mL additionally received 1mg hydroxycobalamine intramuscularly twice a week for the first month only. Serum folate, Cbl and tHcy levels were determined using immunoassays methods at the beginning and the end of the study period. The MTHFR C677T and MTHFR A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. At the end of the 3-month intervention period, the levels of serum folate and Cbl increased significantly, whereas the levels of serum tHcy decreased significantly in the two groups. The individuals with MTHFR 677TT genotype had a significantly higher reduction in serum tHcy levels than the individuals with the MTHFR 677CC or MTHFR 677CT genotypes. Although the "Folinic acid Group" had a considerably higher increase in their serum folate levels (but not Cbl) than the "l-methylfolate Group", the reduction of serum tHcy levels between the two groups was not substantially different. The individuals with MTHFR 677CT genotype had a statistically significant higher reduction in serum tHcy levels when supplemented with folinic acid rather than l-methylfolate. The administration of folinic acid compared to l-methylfolate caused a higher increase of serum folate levels but no difference in the reduction of serum tHcy levels. The reduction of serum tHcy levels was influenced by the existence of MTHFR C677T and not MTHFR A1298C gene polymorphisms. The individuals with MTHFR 677CT genotype appear to benefit more by folinic acid than l-methylfolate supplementation.

P10-026-23 The Association of MTHFR Gene C677T Polymorphism and Daily Dietary Folate Intake With the Risks of Nonalcoholic Fatty Liver Disease

P10-026-23 The Association of MTHFR Gene C677T Polymorphism and Daily Dietary Folate Intake With the Risks of Nonalcoholic Fatty Liver Disease

Role of MTHFR 677C>T and 1298A>C gene polymorphisms on renal toxicity caused by lead exposure in wastewater treatment plant workers

Environmental and occupational lead (Pb) exposures continue to pose major public health problems. Wastewater treatment plant (WWTP) workers proved are exposing to high Pb concentrations in sludge departments. The aim of the work was to investigate the role of MTHFR C677T and MTHFR A1298C gene polymorphisms on alteration of oxidative stress and homocysteine levels in WWTP workers exposed to high Pb concentrations, and study its relations with renal functions. The study included 90 WWTP workers from Abu-Rawash WWTP. Homocysteine, creatinine, urea, malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured. Polymorphisms of MTHFR C677CT and MTHFR A1298C genes were studied using PCR/RFLP. Urine Pb concentrations were also measured. About 32.2% of the workers were with detectable Pb levels. Pb, homocysteine, and MDA levels were significantly higher among workers carrying TT polymorphism compared to other MTHFR C677T gene polymorphisms, while TAC was significantly lower among them compared to other polymorphisms. The same results were found among workers carrying CC compared to other MTHFR A1298C gene polymorphisms. WWTP workers carrying MTHFR 677TT and MTHFR 1298CC are more susceptible to elevation of homocysteine and the urinary Pb compared to the workers with the other polymorphisms. Furthermore, those workers were found to have increase in urea and creatinine. Therefore, MTHFR C677T and MTHFR A1298C gene polymorphisms could be used for prediction of the susceptibility to the risk of kidney impairments among WWTP workers in the sludge departments caused by their exposure to high Pb in their workplace.

FOLINIC ACID OR L-METHYLFOLATE SUPPLEMENTATION FOR THE TREATMENT OF HYPERHOMOCYSTEINEMIA

Objective: Hyperhomocysteinemia (HHcy) is recognized as a risk factor for for cardiovascular disease. The aim of this study was to investigate and compare the efficacy of two tHcy-lowering treatments including FNA or L-methylfolate in healthy Greek adults. Design and method: Two hundred and seventy two (272) health Greek adults (143 men; mean age±SD: 43.0±15.3 years), with elevated serum tHcy levels (&gt;10 mmol/L) received randomized folinic acid (Group 1) or L-methylfolate (Group 2) orally both with hydroxycobalamine im for three months. Serum folate, Cbl and tHcy levels were determined using immunoassays methods at the beginning and the end of the study period. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. Results: At the end of the 3-month intervention period the levels of serum folate and Cbl were significantly increased, whereas serum tHcy concentrations were significantly decreased in both groups. The individuals with 677TT genotype had significantly higher reduction of serum tHcy levels than individuals with the 677CC or 677CT genotypes. Although the individuals of Group 1 had significantly greater increase of their serum folate levels than those of Group 2, the reduction of serum tHcy concentrations between the two groups did not differ significantly. The individuals with 677CT genotype had statistically significant greater reduction of serum tHcy levels when received folinic acid than methylfolate supplementation. Conclusions: The tHcy-lowering treatment which included FNA supplementation compared to treatment which included L-methylfolate supplementation caused a greater increase of serum folate levels but no difference in reduction of serum tHcy levels. The reduction of serum tHcy levels was influenced by the existence of MTHFR C677T and not A1298C gene polymorphisms. The individuals with 677CT genotype appear to benefit more by the treatment which included FNA than L-methylfolate supplementation.

The Association Between MTHFR C677T Gene Polymorphism and Repeated Pregnancy Loss in Arabic Countries: a Systematic Review and Meta-Analysis.

The role of MTHFR C677T polymorphism in repeated pregnancy loss (RPL) among different populations has been studied with inconsistent results. The study objective was to determine the association between MTHFR C677T polymorphisms and RPL among Arab women. The review included all the available studies investigating the association between MTHFR C677T polymorphism and RPL from 2000 until now. The searched database included Cochrane, Trip, EMBASE, and Google Scholar. Two authors independently reviewed the searched articles for eligibility, judged their risk of bias, and extracted the characteristics of the studies. Review Manager 5.3 program was used for data analysis using odds ratio (OR) at a 95% confidence interval (CI). The study revealed a statistically significant difference between cases and controls regarding combined MTHFR C677T polymorphisms (OR = 1.50, 95% CI = 1.15-1.96), MTHFR C677T heterozygous (OR = 1.41, 95% CI = 1.08-1.83), and MTHFR C677T homozygous (OR = 4.19, 95% CI = 1.87-9.39). Considerable significant heterogeneity was recorded in the three analyses (P < 0.05). The review supported the hypothesis that MTHFR C677T mutation is considered a significant risk factor for RPL among Arab women.

Associations of Serum Total Homocysteine Levels with Various Demographic, Clinical and Genetic Characteristics in Healthy Greek Adults.

The aim of this study was to investigate the association of serum total Hcy (tHcy) levels with various demographic, clinical and genetic characteristics in healthy Greek adults. Anthropometric characteristics (height, weight), systolic and diastolic blood pressure, complete blood count and biochemical assessments, were recorded and measured among 383 Greek adults (199 men). Serum folate, Cobalamin (Cbl) and tHcy levels were determined using immunoassays methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. MTHFR C677T gene polymorphism, serum folate and Cbl levels were correlated with serum tHcy levels independently. The individuals with 677TT genotype had significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. Regarding the MTHFR C677T gene polymorphism, the existence of the T allele was associated with statistically significantly lower serum folate and higher serum tHcy levels than C allele. Regarding the MTHFR A1298C gene polymorphism, the existence of the C allele was associated with statistically significant lower serum tHcy levels than A allele. Furthermore, there was no significant correlation between the serum tHcy levels and demographic (except age) or clinical characteristics (sex, BMI, smoking status, SBP, DBP, HGB, HCT, TC, TG, HDL-C, LDL-C, TC/HDL-C). Serum tHcy levels are influenced by the existence of MTHFR C677T gene polymorphism (mainly 677TT genotype), serum folate and Cbl levels. Individuals with hyperhomocysteinemia should be further investigated for the existence of MTHFR C677T gene polymorphism, with the aim to determine the suitable treatment.

Research Article Lack of significant association between MTHFR gene C677T polymorphism and colorectal cancer in the Azerbaijani population

Research Article Lack of significant association between MTHFR gene C677T polymorphism and colorectal cancer in the Azerbaijani population

Evaluation of homocysteine, folic acid and methylenetetrahydrofolate reductase C677T gene polymorphism associated with recurrent spontaneous miscarriage

This study was aimed to assess the association between evaluation of homocysteine level, folic acid and methylenetetrahydrofolate reductase MTHFR C677T gene polymorphism and recurrent pregnancy loss RSA. Sixty four women diagnosed with RSA and 41 normal fertile female, who had at least one or more child, 21 of them were pregnant women while 20 were non-pregnant. The level of homocysteine was high in women with RSA (11.41+3.75) (p&lt;0.05) compared to normal fertile women either pregnant (7.02+2.13) or non-pregnant (6.84+2.08), low levels of folic acid was observed (6.35+2.09) in women with RSA (p&lt;0.05) compared to fertile women either pregnant(10.08+3.08) or non-pregnant(11.27+3.15). No statistically significant difference was observed in the distribution of genotypes between cases and controls for MTHFR polymorphism. In conclusion, the present study reveals to lack of association of MTHFR C677T polymorphism in RSA women.

Analysis of polymorphisms in recurrent pregnancy loss: Factor V Leiden G1691A, Factor II G20210A, MTHFR C677T and Factor V H1299R

The distribution of factor V Leiden G1691A, factor II G20210A, MTHFR C677T, and factor V H1299R polymorphisms known to predispose to thrombophilia in 215 cases and 40 controls admitted with indication of recurrent pregnancy loss (RPL) was investigated. Genotyping was performed by melting curve analysis using simultaneous PCR (RT-PCR). There was no difference between genotype and allele frequencies in the case and control groups in terms of the polymorphisms examined (p>0.05). In the genotype distribution of the Factor V gene G1691A polymorphism, 12.6% GA in the case group and 90.0% GG (wild) genotypes in the control group were found to be higher than the other genotypes. In the genotype distribution of the factor II gene G20210A polymorphism, the GG (wild) genotype was found to be higher in 94.5% and 97.5%, respectively, in the case group and control group than the other genotypes. In the genotype distribution of MTHFR gene C677T polymorphism, 43.7% CC (wild) in the case group and 40.0% CT genotype in the control group were found to be higher than the other genotypes. In the genotype distribution of the factor V gene A4070G polymorphism, 87.4% AA (wild) in the case group and 80% AA (wild) genotype in the control group were found to be higher than the other genotypes. However, the frequency of risk allele A for factor V Leiden G1691A (6.8% and 5%), the frequency of risk allele A for factor II gene G20210A (3% and 1.2%), MTHFR gene C677T were determined in the case and control groups. The frequency of the T allele (35.9% and 42.5%), which is the risk allele for A4070G, and the frequency of the G allele (6.5% and 16.6%), which is the risk allele for the factor V gene A4070G, were determined. When our study results were evaluated, no relationship was found between RPL and factor V Leiden G1691A, factor II G20210A, MTHFR C677T, and factor V A4070G polymorphisms.

C677T Gene Polymorphism of MTHFR Is a Risk Factor for Impaired Renal Function in Pregnant Women With Preeclampsia in the Chinese Han Population.

Impaired renal function in pregnant women with preeclampsia is particularly common, yet there is no consensus about implementation. This lack of consensus is due in part to uncertainty about risks for disease progression. Limited evidence suggests that C677T gene polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR C677T) may affect impaired renal function in pregnant women with preeclampsia in Chinese Han population. To investigate the association between MTHFR C677T and impaired renal function in pregnant women with preeclampsia, a total of 327 pregnant women diagnosed with gestational hypertension (GH) or preeclampsia-eclampsia (PE) from January 2016 to December 2021 were selected as the study subjects. The personal information, gestational information, clinical indicators, and the C677T gene polymorphism of MTHFR were tested. Compared with the GH group, the PE renal function impairment group had increased in blood pressure, homocysteine level, liver and kidney function indicators (creatinine, uric acid, urea nitrogen, cystatin C, alanine aminotransferase, aspartate aminotransferase, cholyglycine), and blood lipids (total cholesterol, triglycerides and low density lipoprotein) but had reductions in plasma protein (total protein, albumin, globulin, prealbumin), trace elements (calcium and zinc), prothrombin time and fibrinogen. The homocysteine level in the TT genotype was higher than that in the CC and CT genotypes. Binary logistic regression analysis showed that the MTHFR C677T gene polymorphism was associated with PE renal function impairment in the recessive model (OR: 1.620, 95% CI: 1.033–2.541, P < 0.05). These findings show that the C677T gene polymorphism of MTHFR is an independent risk factor for impaired renal function in pregnant Chinese Han women with PE.

Association of methyltetrahydrofolate reductase gene mutation, homocysteine level with semen quality of Iraqi infertile males

BackgroundInfertility is very common condition and almost 50% of cases are due to male factors. Several genetic and environmental factors are responsible for the poor quality and reduced number of sperms in several cases of infertility. The present study was designed to investigate the association between semen parameters, homocysteine, and the risk of C677T polymorphism of MTHFR gene in infertile males of Iraqi population.MethodsThis Case–control study has been conducted from February 2019 to July 2021 at a molecular laboratory in the Anatomy and Histology Department/college of Medicine/University of Kufa/Najaf/Iraq. It was composed of 353 infertile male patients. They were divided into five groups: 90 azoospermic, 84 oligospermia, 64 asthenospermic, 50 oligoasthenospermic, and 65 teratospermic with an age range 20–46 years compared with 100 fertile males as control with age range 21–49 years. In order to detect homocysteine levels, we used Hcy ELISA Kit. C677T mutation of MTHFR gene was employed by PCR–RFLP technique.ResultsOur data revealed three genotypes of MTHFR C677T, 167 (47.3%) subjects had CC genotype, 116 (32.9%) subjects had CT genotype and 70 (21.1%) subjects had TT genotype. Furthermore, T allele was associated with higher risk of infertility in all patients groups for any genetic model. In total infertile subjects (codominant model: CT vs. CC, OR = 2.0, 95% C.I = 1.2–3.3, P = 0.011; TT vs. CC, OR = 4.8, 95% C.I = 3.3–8.2, P = 0.0003; dominant model: CT + TT vs. CC, OR = 2.8, 95% C.I = 1.7–4.5, P = 0.0001). Oligoasthenospermic patients associated with higher risk in CT heterozygous genotype (OR = 2.8, 95% C.I = 1.0–4.9, P = 0.03) and TT homozygous of mutant allele (OR = 6.3, 95% C.I = 1.9–9.2, P = 0.002). Homocystein level was elevated in all infertile groups when compared with control group (P < 0.01), but the elevation was marked in oligoasthenospermia group. As well as, the level of Serum Hcy exhibited the highest value in TT mutant genotype (39.7 µmol/ml) followed by CT genotype (28.5 µmol/ml) while the lowest level of Hcy recorded in CC genotype (14.6 µmol/ml) for oligoasthenospermia group.ConclusionsBy relating the MTHFR C677T gene mutation with a higher homocystein level, the results showed that Iraqi males with this mutation are more likely to suffer from infertility.

Association between MTHFR C677T and A1298C gene polymorphisms and maternal risk for Down syndrome: A protocol for systematic review and/or meta-analysis.

Background:Down syndrome (DS) is one of the most common chromosomal abnormalities among live-born babies and one of the best-known intellectual disability disorders in humans. Errors leading to trisomy 21 are primarily arising from defects in chromosomal segregation during maternal meiosis (about 88% of cases), and the focus of many investigations has been to identify maternal risk factors favoring chromosome 21 malsegregation during oogenesis. Maternal polymorphisms of genes required for folate metabolism are the most investigated risk factors for the birth of children with DS. Through this review, we sought to investigate the association of the polymorphisms “C677T” and “A1298C” of the MTHFR gene with maternal risk for DS.Methods:We will use the databases PubMed, Embase, Scopus and Web of Science to search for case-control studies published from 1999 up to September 2021 without language restriction. Results will be presented as relative risks and 95% confidence intervals for dichotomous outcomes and mean differences, or standardized mean differences along with 95% confidence intervals, for continuous outcomes. The all data synthesis will be analyzed on the Review Manager 5.2 version software.Results:This study will be able to clarify all the doubts we seek and that it will be able to provide accurate data that will be able to describe how these polymorphisms can act to increase the predisposition for the birth of children with DS in different populations and under different dietary conditions.Conclusions:This study will clarify the relationship between C677T and A1298C polymorphisms MTHFR gene with increased the maternal risk for Down syndrome.Registration:This systematic review and meta-analysis protocol has been registered on the Prospective Registry of International Systematic Review and Meta-analyses: CRD42021269338.

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

Previous epidemiological data linking the C677T and A1298C MTHFR polymorphisms to gestational diabetes risk have been mixed and controversial. Therefore, we conducted this meta-analysis to derive a more precise estimation of the relationship between MTHFR polymorphisms and this pregnancy disorder. A systematic literature search for original epidemiological studies was performed in the CNKI, WanFang, Cochrane Library, PubMed, and Web of Science databases. R language-based programs were employed for all statistical analyses. Odds ratios and corresponding 95% confidence intervals were calculated to estimate the effects of the variant allele on gestational diabetes risk. A summary of the estimates for the C677T polymorphism showed that the exposure cohorts were prone to gestational diabetes by a greater magnitude than the control groups. Further subgroup analysis by ethnicity showed that the Asians carrying the variant T allele were more susceptible to this pregnancy disorder. However, the pathogenic effect was not evident in the non-Asian subgroup. For the A1298C polymorphism, no statistical significance could be detected. This meta-analysis suggests that the T allele of the MTHFR gene C677T polymorphism tends to increase gestational diabetes susceptibility, especially for Asians. However, the A1298C polymorphism is not associated with an increased risk of this crippling pregnancy disorder.

Relation Between Methylenetetrahydrofolate Reductase Polymorphisms (C677T and A1298C) and Migraine Susceptibility.

Migraine is a neurological disorder which impairs the patient's quality of life. Several association studies investigating the association between MTHFR gene C677T and A1298C polymorphisms and susceptibility to migraine were published. But the results were conflicting, so authors performed a meta-analysis of published case control studies to find out the exact association between MTHFR polymorphism and migraine susceptibility. Four databases were searched for suitable studies up to December, 2018. Odds ratios (OR) with 95% confidence intervals (CI) was calculated adopting additive, homozygote, co-dominant, dominant, and recessive genetic models. Results of MTHFR C677T polymorphism studies meta-analysis showed significant association with migraine risk using allele contrast, homozygote, dominant and recessive genetic models (T vs. C: OR = 1.18, 95% CI = 1.00-1.26, p = 0.05; TT vs. CC: OR = 1.24, 95% CI = 1.0-1.5, p = 0.04; CT vs. CC: OR = 1.08, 95% CI = 0.97-1.07, p = 0.25; TT + CT vs. CC: OR = 1.15, 95% CI = 1.0-1.29, p = 0.04; TT vs. CT + CC: OR = 1.97, 95% CI = 1.28-3.42, p = 0.002). However, results of MTHFR A1298 polymorphism studies meta-analysis did not show any association with migraine. Subgroup analysis based on ethnicity and migraine types i.e. migraine with aura (MA) and without aura (MO) were also performed. Results of present meta-analysis indicate overall association between MTHFR C677T polymorphism with migraine in total 24 studies, in Asian population and in MA cases but did not show any association with Caucasian population and MO cases.

Methylenetetrahydrofolate reductase C677T gene polymorphism in hepatitis C virus-related hepatocellular carcinoma: an Egyptian perspective

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It constitutes a major health problem in both developed and developing countries. In Egypt,the incidence of HCC is remarkedly increasing because of the high prevalence of hepatitis C viral infection. In this study, we investigated whether methylenetetrahydrofolatereductase (MTHFR) C677T polymorphism has a role in the development of HCC in Egyptians. We recruited 128 patients diagnosed with HCC from the Hepatology and Gastroenterology Department, Mansoura Specialized Medical Center, MansouraUniversity Hospitals at the Delta region of Egypt. In addition, a total of 130participants who were confirmed as having hepatitis C viral infection constituted the other group in this study. The genotypes and allele distributions in both groups were investigated using PCR-RFLP and were compared. On comparing the frequency of alleles, genotypes in two patient groups revealed statistical significance for MTHFRC677T gene polymorphism in HCC patients. The CT and TT genotype and the T allele of MTHFR C677T gene polymorphism all showed a significant risk of developing HCC [odds ratio (OR)=1.92; 95% confidence interval (CI)=1.11–3.32; P=0.019; (OR=4.91; 95% CI=1.32–18.24; P=0.018); (OR=2.113; 95% CI=1.36–3.29; P=0.001), respectively].