Methylenetetrahydrofolate Reductase C677T Polymorphism Research Articles

Effects of MTHFR genetic polymorphism on inflammatory protein osteopontin in RA patients: A gender based study in North Indian population

BackgroundRheumatoid arthritis (RA) is a systemic chronic inflammatory disease that ultimately damages bone and cartilage of joints leading to disability. Genetic polymorphism in methylene tetrahydrofolate reductase (MTHFR) gene has been identified as potential marker of susceptibility or disease severity in RA. Risk of RA is three times higher in women than men. Several cytokines and proteins play significant role in synovitis of RA patients. Osteopontin (OPN) is the pro-inflammatory cytokine reported to be associated with synovitis in RA, as it generates T-helper-1 (TH1)-mediated cellular immune response. ObjectiveTo study the impact of MTHFR gene polymorphism on the serum levels of OPN in RA patients and to investigate the cause of greater disease severity in women than men. Patients and methodsThe study included sixty RA patients (eleven men and forty-nine women) from different regions of Uttar Pradesh, North India. OPN was estimated by using enzyme-linked immunosorbent assay and other serological parameters such as Serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), C-reactive protein (CRP), triglycerides (TGA), cholesterol, uric acid, albumin and total protein were estimated using commercially available kits. MTHFR A1298C and C677T polymorphism was genotyped using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) based assays. Disease activity score and health questionnaire was assessed in all patients. ResultsMean age of patients was 44.53 ± 1.59 in women and 46.27 ± 4.22 in men with greater duration of morning stiffness in women than men. There were differences in TJC, SJC and DAS-28 score between men and women. OPN levels were found significantly higher in women than men. Other serological parameters were insignificantly higher in women than men. Genotypic study revealed that MTHFR genotypes are not associated with serum OPN levels. However, the disease activity scores (DAS-28), total joint count (TJC) and swollen joint count (SJC) were significantly associated with 1298CC genotype. Frequency distribution of MTHFR gene between men and women indicates that 1298CC genotype was more frequent in women than men and hence it might be one of the factors to cause disease severity more in women than men. ConclusionA1298C polymorphism is a predictor to the disease severity in RA patients. Patients with homozygous mutant CC genotype have a higher DAS-28 score along with TJC and SJC. The significantly higher OPN levels in female subjects suggest that disease severity is more in women than men. However, other parameters such as SGOT, SGPT, CRP, TGA, creatinine, uric acid, albumin and total protein were higher in women but the change was insignificant.

Associations Between Gestational Diabetes Mellitus Risk and Folate Status in Early Pregnancy and MTHFR C677T Polymorphisms in Chinese Women.

PurposeRed blood cell (RBC) folate indicates long-term folate intake, and methylenetetrahydrofolate reductase (MTHFR) gene is the main gene affecting folate status. Increasing evidence suggests an association between gestational diabetes mellitus (GDM) and increased folate levels. Whether RBC folate concentrations in the first trimester of pregnancy or polymorphisms of MTHFR C677T (rs1801133) affect GDM risk in Chinese pregnant women remains unknown. Therefore, we analyzed the associations of RBC folate concentrations and rs1801133 polymorphisms with GDM risk among pregnant women in China.MethodsA total of 366 women with a singleton pregnancy were followed prospectively from their first prenatal visit to delivery. RBC folate concentrations and rs1801133 polymorphisms were assessed during the first trimester of pregnancy. Binary logistic regression analyses were performed to determine the odds ratios (ORs) of GDM and 95% confidence intervals (CIs) by using the RBC folate concentration quartiles and rs1801133 polymorphisms.ResultsParticipants with the TT genotype had the highest RBC folate concentrations. Those with heterozygous or homozygous variants did not have a significantly higher risk of GDM than did women with C alleles. After adjustments for covariates, women in the highest quartile for RBC folate concentration had a higher risk of GDM (adjusted OR = 2.473, 95% CI = 1.013–6.037, P = 0.047) than did those in the lowest quartile, but this association was nonsignificant after adjustment for rs1801133 polymorphisms.ConclusionHigher RBC folate, partly caused by MTHFR 677C→T, may be associated with increased GDM risk, even in early pregnancy. Assessing RBC folate status and appropriately supplementing folate during early pregnancy, particularly for patients with MTHFR 677C→T, may prevent GDM. Further studies with larger populations are warranted.

Riboflavin supplementation alters global and gene-specific DNA methylation in adults with the MTHFR 677 TT genotype

DNA methylation is important in regulating gene expression and genomic stability while aberrant DNA methylation is associated with disease. Riboflavin (FAD) is a cofactor for methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate recycling, which generates methyl groups for homocysteine remethylation to methionine, the pre-cursor to the universal methyl donor S-adenosylmethionine (SAM). A polymorphism (C677T) in MTHFR results in decreased MTHFR activity and increased homocysteine concentration. Previous studies demonstrated that riboflavin modulates this phenotype in homozygous adults (MTHFR 677 TT genotype), however, DNA methylation was not considered. This study examined DNA methylation, globally and at key MTHFR regulatory sites, in adults stratified by MTHFR genotype and the effect of riboflavin supplementation on DNA methylation in individuals with the 677 TT genotype. Samples were accessed from participants, screened for the MTHFR C677T polymorphism, who participated in observational (n = 80) and targeted riboflavin (1.6 mg/day) RCTs (n = 80). DNA methylation at LINE-1 and key regulatory regions of the MTHFR locus were analysed by pyrosequencing in peripheral blood leukocytes. LINE-1 (+1.6%; p = 0.011) and MTHFR south shelf (+4.7%, p < 0.001) were significantly hypermethylated in individuals with the MTHFR 677 TT compared to CC genotype. Riboflavin supplementation resulted in decreased global methylation, albeit only significant at one CpG. A significant reduction in DNA methylation at the MTHFR north shore (−1.2%, p < 0.001) was also observed in TT adults following intervention with riboflavin. This provides the first RCT evidence that DNA methylation may be modulated by riboflavin in adults with the MTHFR 677 TT genotype.

Combined effect of polymorphisms of MTHFR and MTR and arsenic methylation capacity on developmental delay in preschool children in Taiwan.

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are related to cognitive dysfunction and mental disability. These genes, along with folate and vitamin B12 levels, are regulators of one-carbon metabolism, which synthesizes S-adenosylmethionine (SAM) as a methyl donor for arsenic methylation. The aim of this study was to explore whether polymorphisms of MTHFR and MTR influence arsenic methylation capacity and plasma folate and vitamin B12 levels and if these influences cause developmental delay in preschool children. A total of 178 children with developmental delay and 88 without developmental delay were recruited from August 2010 to March 2014. A high-performance liquid chromatography-hydride generator and atomic absorption spectrometer were used to determine urinary arsenic species. Plasma folate and vitamin B12 concentrations were measured by SimulTRAC-SNB radioassay. Polymorphisms of MTHFR C677T, MTHFR A1298C, and MTR A2756G were examined by polymerase chain reaction and restriction fragment length variation. The results show that MTHFR C677T C/T and T/T genotypes had a lower risk of developmental delay than the C/C genotype (odds ratio [OR] = 0.47; 95% confidence interval, 0.26-0.85). Subjects with the MTHFR C677T C/C genotype had significantly lower plasma folate and vitamin B12 levels than those with the MTHFR C677T C/T and T/T genotype. The MTHFR C677T C/C genotype combined with high total urinary arsenic and poor arsenic methylation capacity indices significantly increased the OR of developmental delay in a dose-response manner. This is the first study to show the combined effect of MTHFR C677T genotype and poor arsenic methylation capacity on developmental delay.

The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment.

In an elderly population with cognitive impairment, we investigated the association between serum uric acid (sUA) and serum homocysteine (sHcy), known risk factors for cerebrovascular disease. We also investigated the potential effect of the C677T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) to the sUA level in different dementia types. Participants underwent a battery of tests including measurements of sUA, sHcy, folic acid, and vitamin B12 as well as genotyping of the MTHFR locus. Data from 861 subjects (597 females to 264 males) were retrospectively analyzed. Subjects with hyperhomocysteinemia had lower serum folic acid and vitamin B12 and higher sUA than those with normal sHcy. sUA was significantly associated with serum creatinine, HbA1c, and sHcy regardless of gender. The TT genotype was found to be associated with hyperhomocysteinemia in both genders (p = 0.001). The levels of hyperlipidemia, sHcy, and sUA differed according to dementia subtypes. High sUA were associated with hyperhomocystenemia in TT genotype only in dementia with vascular lesion. This study reveals that sUA is positively associated with sHcy. We speculate that the two markers synergistically increase cerebrovascular burden and suggested that dietary intervention for sUA and sHcy would be helpful for cognitive decline with vascular lesion.

Methylenetetrahydrofolate reductase C677T polymorphism and toxicity to 5-FU-based chemotherapy in colorectal cancer

Purpose: To investigate the toxicity of methylenetetrahydrofolate reductase (MTHFR) polymorphism in colorectal cancer patients treated with 5-fluorouracil (5-FU).Methods: A total of 105 patients with colorectal cancer who underwent 5-FU therapy were included in this study. MTHFR C677T polymorphisms were determined using direct sequencing. Physical examination and the results of blood and urine tests were used to evaluate the toxicities, including gastrointestinal toxicity, hematopoietic toxicity, hair-skin toxicity and hand-foot syndrome.Results: In 90.5 % of all patients, 5-FU toxicity was observed. With regard to MTHFR C677T mutation, 45.7 % heterozygote mutants and 19.0 % homozygote mutants were observed. MTHFR C677T polymorphism was statistically related to 5-FU toxicity (p = 0.000). In addition, MTHFR C677T mutation was closely related to hematopoietic toxicity (p = 0.005).Conclusion: MTHFR C677T can be used for the prediction of 5-FU toxicity, and can also predict hematopoietic toxicity in patients with colorectal cancer.&#x0D; Keywords: MTHFR genes, Polymorphism, Colorectal cancer, Biomarker, Toxicity

Assessment of the relationship between methylenetetrahydrofolate reductase polymorphism and acute lymphoblastic leukemia: Evidence from an updated meta-analysis.

The methylenetetrahydrofolate reductase gene C677T polymorphism is closely related to the acute lymphoblastic leukemia. Several case-control studies have investigated this association; however, no conclusions could be drawn. A comprehensive updated meta-analysis is established to explain these contradictions and clarify the overall impact of this variant on the susceptibility to acute lymphoblastic leukemia. Electronic searches were conducted to select published studies prior to June 2018. Pooled odds ratios and stratification analysis were performed under different genetic comparison models, age, and ethnicity. Totally, 66 case-control studies including 9619 acute lymphoblastic leukemia cases and 17,396 controls were selected. Our analyses showed that methylenetetrahydrofolate reductase C677T polymorphism was protective mainly in Asian and European countries, under all genetic models and regardless of age, but leukemogenic in mixed population. Thus, C677T polymorphism may be a promising acute lymphoblastic leukemia biomarker, but they should be interpreted with caution considering other factors such as folic acid intake, gene-gene and gene-environment interactions.

Methylenetetrahydrofolate Reductase C677T Gene Polymorphism as a Risk Factor for Hypertension in a Rural Population.

Hypertension remains a public health burden despite advances in its management. Hence, the search for further risk stratification tools and prevention and new treatment approaches continues. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with hypertension. Interestingly, riboflavin, as a cofactor of MTHFR, may control blood pressure in patients with mutant MTHFR variants. These double benefits of a risk stratification tool and treatment approach make it interesting. Because this polymorphism depends on ethnicity and geographic region, we aimed to determine the association between MTHFR C677T gene polymorphism and hypertension in a rural Indonesian-Sundanese population. This population-based case-control study included 213 hypertensive subjects and 202 nonhypertensive subjects as controls. The TaqMan assay was used to determine the MTHFR C677T genotypes. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the risk of association. There was a significant difference in MTHFR C677T allele frequencies between the hypertensive and control groups (62.9% CC, 34.3% CT, 2.8% TT vs. 77.7% CC, 20.8% CT, 1.5% TT; p=0.004) and between mutant (TT and CT) and wild-type genotypes (CC) (p=0.001). The mutant genotype was associated with a risk of hypertension (OR 2.1; 95% CI 1.3–3.5) when adjusted for age, body mass index, waist circumference, and diabetes mellitus. The mutant of the MTHFR C677T gene increases the risk of hypertension in rural Indonesian-Sundanese population. These findings may be used in future studies to evaluate the effect of riboflavin supplementation in this population.

Methylene tetrahydrofolate reductase and methionine synthase gene polymorphisms as genetic determinants of pre-eclampsia.

Pre-eclampsia (PE) is a leading cause of maternal and neonatal mortality in Africa; and has been associated with the interplay of genetic, metabolic and environmental factors. Polymorphisms of methylene tetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) folate cycle genes, have been controversially associated with pre-eclampsia in studies from different human populations. To determine the distribution of MTHFR C677T and MTR A2756G polymorphisms in a Nigerian population and evaluate possible associations with the occurrence of pre-eclampsia and homocysteine metabolic derangement. This study was a hospital based study carried out in Lagos, South-western Nigeria. Two hundred pregnant women clinically diagnosed with pre-eclampsia (study group) and 200 apparently healthy non-pre-eclamptic pregnant women (control group) were recruited for the study after written informed consent. Pre-eclampsia was diagnosed based on the International Society for the Study of Hypertension in Pregnancy re-classification of 2013. MTHFR C677T and MTR A2756G polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analyzes were performed using SPSS version 23. Hardy-Weinberg distribution were tested with χ2 test. Logistic regression model was used to evaluate the relationship of variables with pre-eclampsia. A value of p<0.05 was considered statistically significant. MTHFR genotype frequencies of CC, CT and TT were 59.8%; 31.2% and 9.0% in study group and 76.6%; 22.3% and 1.0% in the control group respectively. MTR A2756G genotype frequencies of AA, AG and GG genotypes were 71.9%; 20.1% and 8.0% for the study group and 81.5%; 16.4% and 2.1% for the control group. Occurrence of pre-eclampsia was significantly associated with presence of T allele of MTHFR (OR=1.855; p<0.05) and G allele of MTR genes (OR=1.269; p<0.05), Homozygosity of TG haplotype significantly increased the occurrence of pre-eclampsia among Nigerian women (OR=2.252; p<0.05). Population attributable risk fraction percent for the T and G alleles were 16.4% and 11.5% respectively. Mean plasma Hcy level was not, however, significantly affected by MTHFR/MTR haplotypes (F=1.54; p=0.157). MTHFR C677T and MTR A2756G polymorphisms were associated with pre-eclampsia in a population of pregnant women in Lagos, Nigeria.

Association of methylenetetrahydrofolate reductase C677T and reduced-f carrier-1 G80A gene polymorphism with preeclampsia in Sudanese women

ABSTRACT Purpose To assess the associations between preeclampsia, methylenetetrahydrofolate reductase (MTHFR) C677T, and reduced folate carrier-1 (RFC-1) G80A gene polymorphism in Sudanese women. Methods A matched (for age and parity) case–control study was conducted in a tertiary hospital (Saad Abualila) in Khartoum, Sudan during February to September 2018. The cases were women with preeclampsia and healthy pregnant women were the controls (160 women in each arm of the study). Genotyping for MTHFR C677T and RFC-1 G80A was performed by polymerase chain reaction–restriction fragment length polymorphism. Results . . The MTHFR C677T variation was significantly more frequent in women with preeclampsia (16.2%) than in healthy pregnant women (1.8%) (OR = 10.1, 95% CI = 3.0–34.2, P < 0.001). There was borderline significance in the RFC-1 G80A variation, which was present in 2.50% of women with preeclampsia, but was not found in healthy pregnant women (P = 0.052). Conclusion s: A higher prevalence of MTHFR C677T polymorphism in women with preeclampsia compared with healthy pregnant women suggests involvement of this variation in preeclampsia in Sudan.

Methylenetetrahydrofolate reductase C677T polymorphism is not associated with the risk of nonsyndromic cleft lip/palate: An updated meta-analysis

Both genetic and environmental factors affect the risk of orofacial clefts. The present meta-analysis aimed to evaluate the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and risk of nonsyndromic cleft lip/palate (NSCL/P) in cases-control studies. The PubMed/Medline, Scopus, Web of Science, and Cochrane Library databases were searched up to April 2019 with no restrictions. The odds ratios (ORs) and 95% confidence intervals (CIs) in all analyses were calculated by Review Manager 5.3 software. The funnel plot analysis was carried out by the Comprehensive Meta-Analysis version 2.0 software. Subgroup analysis, meta-regression, and sensitivity analysis were performed for the pooled analyses. Thirty-one studies reviewed in this meta-analysis included 4710 NSCL/P patients and 7271 controls. There was no significant association between MTHFR C677T polymorphism and NSCL/P susceptibility related to allelic model (OR = 1.04; P = 0.49), homozygote model (OR = 1.11; P = 0.35), heterozygote model (OR = 0.99; P = 0.91), dominant model (OR = 1.00; P = 0.96), or recessive model (OR = 1.08; P = 0.23). There was no significant association between MTHFR C677T polymorphism and NSCL/P susceptibility based on the ethnicity or the source of cases. There was a significant linear relationship between the year of publication and log ORs for the allele model. The results of the present meta-analysis failed to show an association between MTHFR C677T polymorphism and NSCL/P susceptibility. The subgroup analyses based on the ethnicity and the source of cases further confirmed this result.

Food Intervention with Folate Reduces TNF-α and Interleukin Levels in Overweight and Obese Women with the MTHFR C677T Polymorphism: A Randomized Trial

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism associated with body fat accumulation could possibly trigger an inflammatory process by elevating homocysteine levels and increasing cytokine production, causing several diseases. This study aimed to evaluate the effects of food intervention, and not folate supplements, on the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in overweight and obese women with the MTHFR C677T polymorphism. A randomized, double-blind eight-week clinical trial of 48 overweight and obese women was conducted. Participants were randomly assigned into two groups. They received 300 g of vegetables daily for eight weeks containing different doses of folate: 95 µg/day for Group 1 and 191 µg/day for Group 2. MTHFR C677T polymorphism genotyping was assessed by digestion with HinfI enzyme and on 12% polyacrylamide gels. Anthropometric measurements, 24-h dietary recall, and biochemical analysis (blood folic acid, vitamin B12, homocysteine (Hcy), TNF-α, IL-1β, and IL-6) were determined at the beginning and end of the study. Group 2 had a significant increase in folate intake (p < 0.001) and plasma folic acid (p < 0.05) for individuals with the cytosine–cytosine (CC), cytosine–thymine (CT), and thymine–thymine (TT) genotypes. However, only individuals with the TT genotype presented reduced levels of Hcy, TNF-α, IL-6, and IL-1β (p < 0.001). Group 1 showed significant differences in folate consumption (p < 0.001) and folic acid levels (p < 0.05) for individuals with the CT and TT genotypes. Food intervention with folate from vegetables increased folic acid levels and reduced interleukins, TNF-α, and Hcy levels, mainly for individuals with the TT genotype.

MTHFR-C677T Gene Polymorphism and Susceptibility to Acute Lymphoblastic Leukemia in Children: A Meta-Analysis.

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) and childhood acute lymphoblastic leukemia (ALL) is inconsistent. To explore the relationship between MTHFR-C677T polymorphism and susceptibility to childhood ALL. PubMed, EMBASE, Web of Science, CNKI, Wanfang, VIP, and other databases were searched from the establishment of the database to November 2019, and all the case-control studies that met the inclusion criteria were collected. Stata 15.0 was used for meta-analysis, with calculation of the odds ratio (OR) of the relationship between MTHFR-C677T polymorphism and childhood ALL susceptibility. Ethnicity was analyzed by subgroup analysis. A total of 26 studies were included in this meta-analysis, including 4,682 children with ALL and 7144 controls. The results showed that there was no significant difference in the comparison of population of allele model, dominant gene model, recessive gene model, homozygous gene model, heterozygous gene model, and the comparison of Caucasian children. The results of the Asian child analysis suggested that the combined OR of the dominant gene model (CC + CT versus TT), homozygous model (CC versus TT) and heterozygous model (CT versus TT) was 1.32 (95% confidence interval [CI]: 1.03-1.70), 1.37 (95% CI: 1.02-1.84), and 1.27 (95% CI: 1.01-1.59), respectively, with statistically significant differences. However, there was no significant difference between the allele model and recessive gene model among Asian children. The MTHFR C677T polymorphism is related to ALL in children, especially in Asian children. CC + CT, CC, and CT genotypes can increase the risk of ALL, but no association has been found in Caucasian children.

LINE-1 Methylation in Chronic HBV Infected Patients: Association with HCC, Gender and MTHFR C677T Polymorphism.

Polymorphism of methylene tetrahydrofolate reductase (MTHFR) C677T has been reported to be associated with HBV-related hepatocellular carcinoma (HCC) risk. However, the underlying mechanism remains elusive. DNA methylation has been suggested to be associated with HCC onset. MTHFR is the key enzyme in folic acid metabolism, thus, it influences the production of the main donor of methyl groups for DNA methylation. This study aimed to determine the association of global DNA methylation with MTHFR C677T polymorphism in chronic HBV infected patients, as well as its association with HCC and gender. In all, 130 chronic hepatitis B (CHB) and 131 HBV-related HCC patients were enrolled in the study. The methylation level of long interspersed nuclear element-1 (LINE-1), the surrogate marker of global DNA methylation, and MTHFR C677T genotypes were determined. The HCC group showed significantly lower LINE-1 methylation than the CHB group (p = 0.016). Females were observed to have a markedly lower LINE-1 methylation level than males in both CHB and HCC groups (p = 0.000, p = 0.014, respectively). A significant relationship between MTHFR C677T polymorphism and LINE-1 methylation was observed in the CHB group (F = 5.985, p = 0.003). CT, TT, and CT + TT genotypes were significantly associated with lower LINE-1 methylation level compared with the CC genotype (p = 0.005, p = 0.018, p = 0.001, respectively). In addition, the association between MTHFR C677T and LINE-1 methylation was more significant in females (F= 5.036, p = 0.011) than in males (F = 3.083, p = 0.051); further, the association was significant in the subjects older than 60 years (F = 3.865, p = 0.028), but not in the subgroup aged less than 60 years (F = 2.496, p = 0.089). LINE-1 methylation level in chronic HBV infected patients was associated with the occurrence of HBV-related HCC, gender, and MTHFR C677T polymorphism.

MTHFR C677T Polymorphism and risk of nonsyndromic cleft in craniofacial region in a South Indian Population

Introduction: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism was found associated with cleft palate (CP) and cleft lip with or without CP in different populations and only very few studies were conducted in the Indian population. The aim of this case–control study is to detect whether there is any association of C677T MTHFR gene polymorphism with clefts in the craniofacial region, especially with Nonsyndromic cleft lip with cleft palate (NSCLP) in the South Indian population. Material and Methods: The study was conducted on 179 nonsyndromic cleft cases and 130 healthy individuals without cleft were included as controls. To detect the polymorphism, polymerase chain reaction–restriction fragment length polymorphism method was carried out, and the result was analyzed using Chi-square test and binary logistic regression model. Results: Among the cleft cases, 120 were NSCLP and it showed 6.67% CT genotype and 18.33% TT genotype, while in controls, it was 18.46% and 1.54%, respectively. The TT genotype increased the risk of NSCLP (odds ratio [OR] =0.079, 95% confidence interval [CI]: 0.02–0.34, P = 0.0007) and CT genotype decreased the risk (OR = 2.59, 95% CI: 1.11–6.06, P = 0.028). However, CT + TT model had no association with NSCLP when compared to CC genotype. No significant difference was found between other 59 clefts and polymorphism. Discussion and Conclusion: The association of MTHFR C677T polymorphism with NSCLP varies from population to population. Our study found an association between the polymorphism and NSCLP. The TT genotype increased the risk of NSCLP and CT genotype reduced the risk.

Significant association between methylenetetrahydrofolate reductase gene C677T polymorphism with polycystic ovary syndrome risk: A meta-analysis update.

The methylenetetrahydrofolate reductase (MTHFR) may play a pathological role in polycystic ovary syndrome (PCOS). However, the conclusions of published reports on the relationship between the MTHFR C677T polymorphism and PCOS risk remain controversial.To derive a more precise estimation we performed a metaanalysis based on 22 studies that together included 2405 cases and 2419 controls. PubMed, EMBASE, WanFang and the Chinese National Knowledge Infrastructure databases were used to retrieve articles up to up to October 28, 2019. The crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated to evaluate the association.Metaanalysis results showed a significant association between the MTHFR C677T polymorphism and PCOS risk in 3 genetic models (allele model: OR = 1.40, 95% CI = 1.27–1.53; dominant model: OR = 1.47, 95% CI = 1.17–1.85); homozygous model: OR = 1.90, 95% CI = 1.55–2.32). Moreover, significant associations were observed when stratified by ethnicity, source of controls, etiology, and genotype methods.This metaanalysis suggests that the T-allele of the MTHFR C677T polymorphism is associated with an increased risk of PCOS, especially in Asians further studies with larger population sizes are needed to confirm these results.

Intakes and status of riboflavin in a representative sample of Irish adults aged 18–90 years screened for MTHFR C677T polymorphism

AbstractMeta-analyses of epidemiological data report that adults who carry a common polymorphism, the MTHFR 677C→T, in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) have a 40% increased risk of CVD and an 87% increased risk of hypertension. Riboflavin (vitamin B2), in its co-enzymatic form flavin adenine nucleotide (FAD), is required as a co-factor by MTHFR and previous trials in hypertensive patients have shown a blood pressure lowering response to riboflavin supplementation that is specific to individuals homozygous for this polymorphism (TT genotype). Low folate status is commonly reported in adults with the TT genotype however the effect of this genetic variant on riboflavin status has not previously been investigated. The aim of this study, therefore, was to investigate dietary intake and biomarker status of riboflavin by MTHFR genotype in Irish adults using data from the National Adult Nutrition Survey (2008–2010) (www.iuna.net).A 4-day semi-weighed food record was used to collect food and beverage intake data from a representative sample of 1500 Irish adults (18–90 years). Dietary intake data were analysed using WISP© based on UK food composition tables (modified to include recipes of composite dishes, nutritional supplements, fortified foods and generic Irish foods that were commonly consumed). Usual intakes were calculated via the NCI-method using SAS© Enterprise Guide. Blood samples (n = 1126) were collected by venepuncture by a trained professional and were processed and analysed using standard operating procedures. Biomarker status of riboflavin was determined by erthyrocyte gluthathione reductase activation coefficient (EGRac), a functional assay that measures the activity of the enzyme glutathione reductase before and after in vitro activation with its prosthetic group FAD; a lower value indicates better status.It was found that 12% of the population had the TT genotype. As expected, there was no significant difference in riboflavin intake across the genotype (CC, CT or TT) groups. Similarly, no significant genotype differences in riboflavin status (EGRac) were observed (1.36 vs 1.37 vs 1.38 respectively). Overall, 61% of the total population had EGRac values &gt; 1.3, indicative of low/deficient status with no significant difference observed between the genotype groups (60%,61% and 61%, respectively).These data suggest that riboflavin status is not influenced by the C677T polymorphism in MTHFR in this cohort of nationally representative Irish adults. Further research is needed to see the impact of riboflavin status on blood pressure across the genotype groups in this nationally representative cohort of Irish adults.

The study of the association between the C677T polymorphism of the methylenetetrahydrofolate reductase gene and severity of symptoms in patients with schizophrenia

To study the association of the C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene with the risk of schizophrenia in a large sample, including schizophrenic patients and mentally healthy people, and to investigate the relationship of this polymorphism with the severity of schizophrenia symptoms and genotype-environment interaction effects on these symptoms. The sample for genotyping consisted of 1357 patients with schizophrenia and schizophrenia spectrum disorders and 711 people of the control group. The severity of symptoms was assessed with the PANSS. Obstetrical complications and a traumatic brain injury in medical history were studied as environmental factors. No association was found between MTHFR C677T polymorphism and schizophrenia. There was no genotype effect on the severity of symptoms on the PANSS subscales. The effect of genotype-environment interactions on the severity of schizophrenia symptoms was not detected. The results do not confirm the data of a number of studies on the relationship of MTHFR C677T polymorphism with schizophrenia symptoms.

Methylenetetrahydrofolate Reductase C677T Polymorphisms as a Risk Factor for Polycystic Ovarian Syndrome in a Sample of Jordanian Women

Methylenetetrahydrofolate Reductase C677T Polymorphisms as a Risk Factor for Polycystic Ovarian Syndrome in a Sample of Jordanian Women

DNA methylation of hypertension-related genes is influenced by the MTHFR 677TT genotype and riboflavin supplementation

AbstractIntroduction:The C677T polymorphism in the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) is associated with hypertension. Riboflavin acts as a cofactor for MTHFR in one-carbon metabolism which generates methyl groups for utilisation in important biological reactions such as DNA methylation. Supplementation with riboflavin has previously been shown to lower blood pressure in individuals with the MTHFR 677TT genotype. The mechanism regulating this gene-nutrient interaction is currently unknown but may involve aberrant DNA methylation which has been implicated hypertension.Objectives:The aims of this study were to examine DNA methylation of hypertension-related genes in adults stratified by MTHFR C677T genotype and the effect of riboflavin supplementation on DNA methylation of these genes in individuals with the MTHFR 677TT genotype.Materials and Methods:We measured DNA methylation using pyrosequencing in a set of candidate genes associated with hypertension including angiotensin II receptor type 1 (AGTR1), G nucleotide binding protein subunit alpha 12 (GNA12), insulin-like growth factor 2 (IGF2) and nitric oxide synthase 3 (NOS3). Stored peripheral blood leukocyte samples from participants previously screened for the MTHFR C677T genotype who participated in targeted randomised controlled trials (1.6mg/d riboflavin or placebo for 16 weeks) at Ulster University were accessed for this analysis (n = 120).Results:There were significant differences in baseline average methylation between MTHFR CC and TT genotypes at NOS3 (p = 0.026) and AGTR1 (p = 0.045) loci. Riboflavin supplementation in the TT genotype group resulted in altered average methylation at IGF2 (p = 0.025) and CpG site-specific alterations at the AGTR1 and GNA12 loci.Conclusion:DNA methylation at genes related to hypertension were significantly different in individuals stratified by MTHFR genotype group. Furthermore, in MTHFR 677TT genotype individuals, there were concurrent alterations in DNA methylation at genes linked to hypertension in response to riboflavin supplementation. This is the largest study to date to demonstrate an interaction between DNA methylation of hypertension-related genes and riboflavin supplementation in adults with the MTHFR 677TT genotype. Further work using a genome-wide approach is required to better understand the role of riboflavin in altering DNA methylation in these genetically at-risk individuals.