MTHFR Polymorphisms Research Articles

Highly sensitive genotyping of MTHFR C677T polymorphisms using a novel RPA-LDR-qPCR assay.

The 5,10-methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in the metabolism of folic acid, synthesis of DNA, and DNA methylation. The genetic polymorphisms of MTHFR caused by the C677T mutation have become an important clinical indicator related to folic acid intake in relevant populations. The most widely used method in clinical practice for genotyping of MTHFR C677T polymorphisms was fluorescence probe PCR, but several flaws of the method hampered its accuracy. This study established a highly sensitive RPA-LDR-qPCR assay for genotyping of MTHFR C677T polymorphisms. It provides an alternative tool for more accurate and reliable diagnosis of folic acid metabolism disorders, and supports the relevant personalized medicine.

Association between MTHFR polymorphism and seizure control in epileptic patients with hyperhomocysteinaemia

The aim of this study was to investigate possible associations between MTHFR polymorphism and seizure control of epileptic patients with hyperhomocysteinaemia. A total of 81 epileptic patients with hyperhomocysteinaemia treated with oxcarbazepine monotherapy were enrolled in this study. All patients were offered vitamin B supplementation (2.5 mg/d folate and 1.5 mg/d mecobalamine) for six months. MTHFR C677T and A1298C polymorphisms, serum homocysteine, folate and vitamin B12 levels as well as seizure frequency and score based on the Hamilton depression scale (HAMD) were evaluated at baseline and after six months of follow-up. Spearman correlation analysis showed that the extent of decline of seizure frequency positively correlated with a dynamic change in serum homocysteine concentration between baseline and after six months of follow-up (t=0.241, p=0.015 [Spearman’s coefficient]). For the MTHFR C677T polymorphism, compared to the CC genotype, the TT genotype was associated with a significant downtrend of homocysteine (19.69 vs 10.28 mmol/L, p=0.006) and uptrend of folate (6.21 vs 2.49 ng/mL; p=0.004). The decrease in homocysteine (17.94 vs 12.52 mmol/L, p=0.001) and increase of folate (5.08 vs 2.86 ng/mL; p=0.003) were significantly greater in patients with the T allele compared to those with the C allele. Also, the TT genotype (2.33 vs 1.4, p=0.056) and T allele (1.95 vs 1.38, p=0.037) were associated with a greater decrease in seizure frequency compared to the CC genotype or C allele. The A1298C polymorphism alone was not associated with elevated homocysteine or decreased folate levels at baseline, and showed little association with response to vitamin B supplementation in epileptic patients with hyperhomocysteinaemia. However, in patients with combined 677TT/1298AA or 677TT/1298AC polymorphisms, the changes in homocysteine and folate levels and seizure frequency were more obvious. MTHFR C677T polymorphism was associated with seizure control in epileptic patients with hyperhomocysteinaemia; individuals with the 677TT genotype or T allele demonstrated better seizure control.

MTHFR C677T polymorphism and cerebrovascular lesions in elderly patients with CSVD: A correlation analysis.

Plasma homocysteine (Hcy) has been identified as a potential risk factor for cerebral small vessel disease. Cerebral small vessel disease (CSVD) leads to cognitive impairment, depression, and other symptoms and is a common disease in middle-aged and elderly people. To investigate the relationship between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and CSVD in elderly patients, plasma levels of homocysteine (Hcy) and MTHFR genotyping were assessed. MRI and MRA were performed at the same time to analyze the relationship between different genotypes and cerebrovascular lesions. We showed that Hcy plasma levels in the TT group were significantly higher than those in the CC and CT groups. Moreover, we observed that the severity of white matter lesions was associated with women and positively correlated with age, previous coronary heart disease, luminal infarction, and MTHFR polymorphism. The multivariate logistic regression analysis showed that age, TT genotype, and lacunar infarction were independent risk factors for white matter hyperintensity (WMH). Importantly, we showed that there was a significant correlation between Hcy plasma levels and MTHFR gene polymorphism, with the TT genotype constituting an independent risk factor for WMH. Therefore, we recommended early detection of MTHFR gene polymorphisms with concomitant early intervention concerning risk factors to delay the occurrence of cognitive impairment in CSVD elderly patients.

The Effect of Dietary Methyl-Donor Intake and Other Lifestyle Factors on Cancer Patients in Hungary.

Simple SummaryThe incidence of cancer has been increasing worldwide and, along with inflammation-related diseases, a significant number of cases could be prevented by appropriate lifestyle routines. Methyl-donors are macronutrients that are important in achieving a healthy balance of metabolic processes. Their deficiency can lead to several symptoms and diseases and has also been implicated in the severity of SARS-CoV-2 infection. Nutrition therapy is already recognized as an appropriate tool in the management of cancer-related fatigue to improve quality of life. In this study, we aimed to explore the potential protective effect of methyl-donor intake in breast, colorectal and pancreatic cancer by patient follow up. Our results suggest that appropriate methyl-donor intake can be useful as an adjunct of conventional oncotherapy which may contribute to improve quality of life. Whether methyl-donor intake supports cancer prevention and patient survival needs further confirmation in large patient cohorts.Background: Nutrition is essential to life and can have an indisputable influence on health and prevention of disease development including cancer. Methyl-donors are macronutrients that are important in achieving a healthy balance of metabolic processes. Their deficiency can lead to several symptoms and diseases—even to severe SARS-CoV-2 infection. We aimed to explore the potential protective effect of methyl-donor intake in breast, colorectal and pancreatic cancer by patient follow up. Methods: A food frequency questionnaire and a diet diary were used to evaluate methyl-donor intake and blood samples were taken to evaluate Il-6 and IL-8 cytokine levels as well as MTHFR (C677T) polymorphism in breast, colorectal and pancreatic cancer patients. Results: We found that levels around the recommended daily intake of B6 and B9 were effective in supporting the overall survival of breast and colorectal, and a relatively higher level of pancreatic adenocarcinoma, patients. The total intake of methyl-donors significantly and negatively correlated with smoking in pancreatic cancer, while folate as well as betaine intake significantly and positively correlated with IL-8 in colorectal cancer patients. Conclusions: Our results suggest that the appropriate intake of methyl-donor can be an adjunct of conventional oncotherapy to improve quality of life. Whether methyl-donor intake supports cancer prevention and patient survival needs further confirmation in large patient cohorts.

Hyperhomocysteinemia in children is an indicator of environmental problems associated with the chоrnobyl exclusion zone

The aim of study: determination of the genetic factor’s involvement (MTHFR:C677T polymorphism), which affects the activity of the main enzyme of the folate cycle, methylenetetrahydrofolate reductase, and environmental exposure, including the radiation factor, in the occurrence of hyperhomocysteinemia in children which living near the Chornobyl Exclusion Zone (ChEZ). Research methods. Immunochemical, mathematical and statistical. Results. Within the framework of international projects, the levels of homocysteine (Hcy) and allelic variants of the genetic polymorphism MTHFR:C677T were determined in 624 children aged 13-17 years old from Ivankivskyi and Poliskyi districts of the Kyiv region. It has been established that an increase in the level of Hcy in the blood and an increase in the number of cases of hyperhomocysteinemia in the examined groups of children are associated with forest fires in the ChEZ in 2015 and 2020. Under conditions of pronounced exposure to radioactive agents and combustion products of forest trees, the proportion of cases of hyperhomocysteinemia in groups of children with and without the T allele of the MTHFR:677 polymorphism in the genome did not have statistical differences. An indicator of ecological trouble in the ChEZ and adjacent areas is an increase, above the physiological level, in the concentration of Hcy in the blood of adolescent children with the absence of the T allele of the MTHFR:677 polymorphism in the genome. Conclusion. In areas affected by the accident at the Chornobyl nuclear power plant, it is necessary to constantly conduct regular monitoring studies of the health of children, using tests for the content of Hcy in the blood and the state of the folate cycle genes.

Developing a Sensitive Platform to Measure 5-Methyltetrahydrofolate in Subjects with MTHFR and PON1 Gene Polymorphisms.

Inadequate levels of 5-methyltetrahydrofolate (5-MTHF) and the T variant of MTHFR C677T have been suggested to be associated with an increased risk of developing mental illness, whereas the PON1 SNP variant provides a protective role. However, reports validating the methodology for plasma 5-MTHF levels in schizophrenia patients are limited. A sensitive LC–MS/MS system using an amide column and calibration curve was determined by dialyzed human plasma, and applied to schizophrenia patients and healthy controls in Taiwan, and the differences between the subgroups were discussed. This analysis system meets regulation criteria, and the lower limit of quantification for 5-MTHF levels was 4 nM from 200 μL plasma, within 7 min. The mean plasma 5-MTHF levels in schizophrenia patients (n = 34; 11.70 ± 10.37 nM) were lower than those in the healthy controls (n = 42; 22.67 ± 11.12 nM) significantly (p < 0.01). 5-MTHF concentrations were significantly lower in male carriers than in female carriers (18.30 ± 10.37 nM vs. 24.83 ± 11.01 nM, p < 0.05), especially in subjects who were MTHFR CT/PON1 Q allele carriers. In conclusion, this quantitative system, which employed sensitive and simple processing methods, was successfully applied, and identified that schizophrenic patients had significantly lower levels of 5-MTHF. Lower plasma 5-MTHF concentrations were observed in male subjects.

Predictive role of &lt;i&gt;MTHFR&lt;/i&gt;, &lt;i&gt;FGB&lt;/i&gt;, &lt;i&gt;F2&lt;/i&gt; and &lt;i&gt;F5&lt;/i&gt; genes polymorphisms in the development of pulmonary embolism

Aim. Research the relationship of gene polymorphisms (MTHFR, FGB, F2, F5) with the development of pulmonary embolism (PE).&#x0D; Material and methods. The study involved 120 people (main group) who underwent PE. Mean age is 63.223.16 years (66 men, mean age 60.243.17 years; 54 women, mean age 66.193.67 years). The control group was composed of Research Institute of Internal and Preventive medicine (Novosibirsk) DNA bank (comparable to the main group by gender and age). This DNA bank was formed during a series of population-based screening. The material for the study includes whole blood, plasma and serum samples, DNA samples, as well as medical records of patients undergoing PE. DNA extraction from venous blood was performed by the phenol-chloroform method. FGA (Del/Ins) rs35496957 was genotyped using polymerase chain reaction (PCR) with flanking primers-8202 A/G, rs11697325 mmp9 using PCR with RFLP. Polymorphisms of genes MTHFR, FGB, F2, F5 were tested by real-time PCR on test systems produced by DNA-technology (Russia) on a DTPrime device (Russia). For structuring and statistical data processing Microsoft Excel and the Microsoft Office software package and the STATISTICA (USA) software package for statistical analysis were used. The study includes the calculation of the following output data and parameters based on the collected incoming statistical data: standard deviation, calculating the mean square value, Pearson's chi-square, likelihood ratios, Fisher's exact test and linear-by-linear association.&#x0D; Results. It was found that the odds ratio of developing PE in men carriers of the TT genotype of the C677T polymorphism of the MTHFR gene at the age of 65 years and older was 4.43 times higher than in carriers of the other two genotypes (95% confidence interval 1.3314.73; p=0.019). There was a tendency of more frequent detection of the genotype GG polymorphism rs1800790 (-455 GA) of the FGB gene among men individuals of the main group compared with the control group (63.6 and 54.0%, respectively). There was also a decrease in the number of respondents with the AA genotype of the rs1800790 polymorphism (-455 GA) of the FGB gene in the group of both genders. There was a tendency of more frequent PE cases among women individuals with genotype GG and GA of the rs1799963 polymorphism of the F2 gene in the main group (85.20 and 14.80%, respectively).&#x0D; Conclusion. Further research of genetic factors role in the occurrence of PE is extremely important for clinical practice taking into consideration the possibility of developing a personalized approach to treatment and prevention of the diseases related to disorders in the hemostatic system.

Investigation of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil related toxicities in colorectal cancer.

Aim: To investigate the association of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil (5-FU) related toxicities and patient survival. Materials & methods: A total of103 colorectal cancer patients prescribed 5-FU were included in the study. Genotyping was conducted for several DPYD, MTHFR and TYMS polymorphisms usinga microarray analyzer. Results: DPYD 496A>G polymorphism was found to be significantly associated with 5-FU related grade 0-2, but not severe toxicities (p=0.02). Furthermore, patients with DPYD 85TC and CC genotypes had longer progression and overall survival times compared toTT genotypes in our study group (log rank=6.60; p=0.01 and log rank=4.40; p=0.04, respectively). Conclusion: According to our results, DPYD 496AG and GG genotypes might be protective against severe adverse events compared to the AAgenotype. Another DPYD polymorphism, 85T>C, may be useful in colorectal cancer prognosis. Further studies for both polymorphisms should be conducted in larger populations to achieve accurate results.

MTHFR Gene-Polymorphism and Infertile Men in Indian Population: A Systematic Literature Review

Single nucleotide polymorphisms (SNPs) in the genetic makeup of the methylenetetrahydrofolate reductase gene (MTHFR C677-T, A1298-C, and G1793-A) alongside environmental and lifestyle component has shown some links as a potential factor responsible for male infertility across the globe posing huge genetic vulnerability to the gender. However, SNPs in the MTHFR gene implicated in male infertility are not without their own controversial results even within the same population. The goal of this study was to provide comprehensive insights into the controversial nature of MTHFR gene polymorphism on male infertility across all Indian populations as well as other ethnicities. The electronic PubMed database was utilized to conduct and select eligible studies for this systematic review (update to December 2021). Only high-quality studies with a link between MTHFR polymorphisms and male infertility were included based on our exclusion and inclusion criteria. The connection between the MTHFR gene polymorphism and male infertility in Indian population studies was evaluated using odds ratios (ORs) with a 95% confidence interval (CI). A total of five studies presenting 1,237 cases and 1,044 controls were assessed for this study. The collective results revealed that MTHFR C667-T and A1298-C gene polymorphism were significantly linked with an increased chance of male infertility both in south India and north India, however, with some conflicting results. Interestingly, no study has been carried out to investigate the impact of G1793-A polymorphism on infertile males in the Indian population at the time of our report. Results generated from the few case-control evaluated on MTHFR gene polymorphism in the Indian population are found to conflict with some extrinsic factors (such as nutritional status-folate metabolism, lifestyle, varying recruitment procedures, and epigenetic elements) identified to have played some critical roles. Therefore, broader studies across all regions in India addressing the grave impact of MTHFR gene polymorphism on male infertility are of utmost importance.

A meta-analysis on the susceptibility to the development of bladder cancer in the presence of DNMT3A, DNMT3B, and MTHFR gene polymorphisms

BackgroundThe etiology of bladder cancer is not yet well known. In this study, we want to evaluate the effect of polymorphisms of genes that have an epigenetic effect (MTHFR, DNMT3A/B) on the susceptibility to develop bladder cancer (BC).MethodsA systematic review was performed for MTHFR, DNMT3A, and DNMT3B, followed by a meta-analysis conducted for rs1801131, rs1801133, rs2274976, rs1550117, and rs1569686 SNPs. A sensitivity and a subgroup analysis were then used.Results20 studies were included, where no statistically significant association between any of the analyzed SNPs and the occurrence of BC was detected. Subgroup analysis revealed a statistically significant association in North African population with rs1801133: TT vs. TC + CC (P = 0.013; OR 95% CI = 0.52 [0.311–0.872]); TT vs.TC (P = 0.003; OR 95% CI = 0.448 [0.261–0.769]) and in North American population with rs1801131: CC vs. CA (P = 0.039; OR 95% CI = 0.71 [0.523–0.984]). A sensitivity analysis revealed that there is a statistically significant association between rs1801131 and the occurrence of BC (OR = 0.79, 95%CI [0.65–0.97]), (OR = 0.80, 95%CI [0.65–0.98]) and (OR = 0.78, 95%CI [0.63–0.96]) which correspond to CC vs. CA + AA; CC vs. CA; and CC vs. AA genetic models.ConclusionThis is the first study to assess the effect of DNMTs on bladder cancer risk. No statistically significant association was found between polymorphisms of MTHFR, DNMT3A/B genes and bladder cancer development, except for the North African and the North American populations with rs1801133 and rs1801131, respectively, with a protective effect of rs1801131 based on a sensitivity analysis.

Association between MTHFR (677C>T and 1298A>C) polymorphisms and psychiatric disorder: A meta-analysis.

Recent studies showed that genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) is related to attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BD) and schizophrenia (SCZ). However, no consistent conclusion has been determined. This meta-analysis aims to interrogate the relationship between MTHFR gene polymorphisms (677C>T and 1298A>C) and the occurrence of ADHD, BD and SCZ. We retrieved case-control studies that met the inclusion criteria from the PubMed database. Associations between MTHFR polymorphisms (677C>T and 1298A>C) and ADHD, BD and SCZ were measured by means of odds ratios (ORs) using a random effects model and 95% confidence intervals (CIs). Additionally, sensitivity analysis and publication bias were performed. After inclusion criteria were met, a total of five studies with ADHD including 434 cases and 670 controls, 18 studies with BD including 4167 cases and 5901 controls and 44 studies with SCZ including 16,098 cases and 19913 controls were finally included in our meta-analysis. Overall, our meta-analytical results provided evidence that the MTHFR 677C>T was associated with occurrence of BD and SCZ, while the 1298A>C polymorphism was related to ADHD and BD, and additionally the sensitivity analysis indicated these results were stable and reliable. This may provide useful information for relevant studies on the etiology of psychiatric disorders.

Different effects of maternal homocysteine concentration, MTHFR and MTRR genetic polymorphisms on the occurrence of fetal aneuploidy

Research questionDo maternal homocysteine (Hcy) concentrations, MTHFR and MTRR genes have effects on the occurrence of fetal aneuploidy? DesignA total of 619 aneuploidy mothers and 192 control mothers were recruited in this study. Differences in distributions of maternal MTHFR 677C>T, MTHFR 1298A>C and MTRR 66A>G genetic polymorphisms and maternal Hcy concentrations between aneuploidy mothers and control mothers were analysed. ResultsThe maternal MTHFR 677C>T polymorphism was found to be a risk factor for the occurrence of many fetal non-mosaic aneuploidies studied here, including trisomies 13, 15, 16, 18, 21, 22, TRA and TS. The maternal MTHFR 1298A>C polymorphism was found to be a risk factor specifically associated with the occurrence of fetal trisomy 15 and fetal TS. The maternal MTRR 66A>G polymorphism was found to be a risk factor only specifically associated with the occurrence of fetal trisomy 21. The Hcy concentrations of mothers of trisomies 22, 21, 18, 16, 15 and TS fetuses were significantly higher than the Hcy concentrations of control mothers. ConclusionsOverall, data suggested an association between these maternal polymorphisms and the susceptibility of fetal non-mosaic trisomy and Turner syndrome. However, these three maternal polymorphisms had different associations with the susceptibility of different fetal aneuploidies, and the elevated maternal Hcy concentration appeared to be a likely risk factor for fetal Turner syndrome and fetal trisomies.

Genetic Variants in Folate and Cobalamin Metabolism-Related Genes in Pregnant Women of a Homogeneous Spanish Population: The Need for Revisiting the Current Vitamin Supplementation Strategies

Polymorphisms of genes involved in the metabolism and transport of folate and cobalamin could play relevant roles in pregnancy outcomes. This study assessed the prevalence of genetic polymorphisms of folate and cobalamin metabolism-related genes such as MTHFR, MTR, CUBN, and SLC19A1 in pregnant women of a homogeneous Spanish population according to conception, pregnancy, delivery, and newborns complications. This study was conducted on 149 nulliparous women with singleton pregnancies. Sociodemographic and obstetrics variables were recorded, and all patients were genotyped in the MTHFR, MTR, CUBN, and SLC10A1 polymorphisms. The distribution of genotypes detected in this cohort was similar to the population distribution reported in Europe, highlighting that more than 50% of women were carriers of risk alleles of the studied genes. In women with the MTHFR risk allele, there was a statistically significant higher frequency of assisted fertilisation and a higher frequency of preeclampsia and preterm birth. Moreover, CUBN (rs1801222) polymorphism carriers showed a statistically significantly lower frequency of complications during delivery. In conclusion, the prevalence of genetic variants related to folic acid and vitamin B12 metabolic genes in pregnant women is related to mother and neonatal outcomes. Knowing the prevalence of these polymorphisms may lead to a personalised prescription of vitamin intake.

Role of polymorphic loci &lt;i&gt;VDR&lt;/i&gt; rs10735810, &lt;i&gt;MTHFR&lt;/i&gt; rs1801131, &lt;i&gt;MTHFR&lt;/i&gt; rs1801133, &lt;i&gt;MTR&lt;/i&gt; rs1805087,&lt;i&gt; MTRR&lt;/i&gt; rs1801394 AND &lt;i&gt;VEGFA&lt;/i&gt; rs3025039 in missed abortion: A prospective cohort study

Background. Premature termination of pregnancy, including miscarriage, remains among the critical problems in modern obstetrics and gynaecology practices. In the context of early gestational failure and the notion that 80% of early miscarriages are triggered by genetic reset — some natural filter — an analysis of current knowledge of the genetic aspects of missed abortion (MA) appears relevant.Objectives. A study of the haplotype frequencies for VDR rs10735810, MTHFR rs1801131, MTHFR rs1801133, MTR rs1805087, MTRR rs1801394 and VEGFA rs3025039 polymorphic loci and their association with vitamin D deficiency in women with missed abortion.Methods. A total of 178 women aged 18 to 41 years were examined. The main cohort consisted of MA patients (n = 101) who were divided between cohort I (n = 58; patients with primary MA) and cohort II (n = 43; patients with recurrent MA). The control cohort (n = 77) consisted of women with a successful pregnancy (Z34.0) entailing a term and live birth. Genotyping of polymorphic loci VDR rs10735810, MTHFR rs1801131, MTHFR rs1801133, MTR rs1805087, MTRR rs1801394 and VEGFA rs3025039 was performed in 177 patients. Total serum 25(OH) D (n = 99) was determined by mass spectrometry. Statistical analysis was carried out using the Statistica v. 10 data analysis software (StatSoft, Russia; TIBCO, USA). Results. No differences were revealed for the frequencies of studied haplotypes between MA women and those who gave birth to healthy full-term newborns (p &gt;0.1). No association was found between first-trimester MA and the presence of polymorphic loci variants (p &gt;0.1). The GG haplotype of gene VDR is even less frequent in recurrent MA patients than in control (14.0% vs. 23.7%; OR = 2.29; 95% CI: 0.738–7.075). The GG haplotype of gene MTR has a 2-fold higher frequency in primary MA patients compared to control, albeit at no statistical significance (8.6 vs. 4.0%). Haplotype TT of the gene VEGF polymorphism occurs even less frequently in primary MA patients than in control (3.5 vs. 7.9%, respectively). Patients with first-trimester MA exhibited an association between vitamin D deficiency and the frequency of polymorphic variants VDR rs10735810 (p = 0.0304) and MTHFR rs1801133 (p = 0.0180). The other studied genes did not reveal such an association.Conclusion. The study demonstrates a pathogenetic association of polymorphic variants VDR rs10735810 and MTHFR rs1801133 with missed abortion and vitamin D deficiency.

Associations of plasma betaine, plasma choline, choline intake, and MTHFR polymorphism (rs1801133) with anthropometric parameters of healthy adults are sex-dependent.

Choline and its metabolites apppear to have relationships with body mass index (BMI), body fat, and body weight, but the research results have proved inconsistent. We thus investigated the associations of plasma levels of trimethylamine N-oxide (TMAO), choline, and betaine with anthropometric measurements, including modulatory effects of genetics and diet. The study was performed on a group of 421 adults, aged 20-40 years, who had been recruited in Poland. Plasma concentrations of choline, betaine, and TMAO were determined using reverse-phase ultra-high-performance liquid chromatography electrospray ionisation mass spectrometry. The following polymorphisms were genotyped using TaqMan probes: rs180113 (MTHFR), rs70991108 (DHFR), rs2236225 (MTHFD1), and rs7946 and rs12325817 (PEMT). We employed multivariate linear regression to examine the associations between anthropometric measurements, one-carbon metabolism metabolites, and genotypes. Higher plasma choline was associated with higher BMI (β = 0.17; p < 0.01), body weight (β = 0.11; p < 0.05), body fat mass (FM) (β = 0.10; p < 0.05), and waist circumference (WC) (β = 0.14; p < 0.01), whereas higher choline intake was associated with lower body FM (β = -0.14; p < 0.01) and lower WC (β = -0.12; p < 0.01). After stratification by sex, plasma betaine was found to be associated with lower BMI (β = -0.20; p < 0.05) and body weight (β = -0.16; p < 0.05) in men only, whereas choline intake was associated with lower body FM (β = -0.19; p < 0.05) and waist-to-hip ratio (WHR) (β = -0.19; p < 0.05) and MTHFR CC genotype was associated with WHR (β = 0.15; p < 0.05) in women only. Higher plasma betaine and higher dietary choline are associated with lower FM and body weight, whereas higher plasma choline is positively associated with body weight status and adiposity. Moreover, these associations appear to be sex-specific.

Genetic control of homocysteine metabolism in children living near the chоrnobyl exclusion zone

The aim of study: to determine the involvement of folate cycle genes in the occurrence of hyperhomocysteinemia in children from Ivankivskyi district of Kyiv region of Ukraine 35 years after the accident at the Chornobyl nuclear power plant. Research methods. Immunochemical, mathematical and statistical. Results. Homocysteine levels were determined in 217 children aged 12-17 from Ivankivskyi district of Kyiv region, as well as genetic polymorphisms of the folate cycle. An excess of homocysteine in the blood over 10 µmol/l (a state of hyperhomocysteinemia) was detected in 65.44 % (142 out of 217) of those examined, among boys – 69.79 % (67 out of 96), among girls – 61.98 % (75 out of 121). The largest proportion of hyperhomocysteinemia cases was registered in the subgroup of children with the basic polymorphism MTHFR: 677TT – 94.44 % of cases. In most cases, hyperhomocysteinemia in children was associated with an environmental factor, including radioactive elements and their decay products. The system for the prevention of hyperhomocysteinemia and its consequences in children living in areas affected by the accident at the Chornobyl nuclear power plant should include regular monitoring of the content of radionuclides in the body of children and locally produced food, the content of homocysteine in the blood, and assessment of the state of folate cycle genes.

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.

Improved Retinal Microcirculation in Mild Diabetic Retinopathy Patients Carrying MTHFR Polymorphisms Who Received the Medical Food, Ocufolin®.

PurposeTo evaluate the effects of Ocufolin® on retinal microcirculation in patients with mild diabetic retinopathy carrying MTHFR polymorphisms.MethodsIn a prospective, case-controlled study, eight patients with mild diabetic retinopathy and MTHFR polymorphisms and 15 normal controls (NC) were recruited. MTHFR polymorphisms were subtyped as normal, C677T, or A1298C. Best-corrected visual acuity (BCVA) was evaluated. Retinal blood flow velocity (BFV) was measured using Retinal Function Imager. Retinal tissue perfusion (RTP, blood flow rate per inner retinal volume) was calculated within a 2.5 mm diameter circle centered on the fovea. The eight retinopathy patients received Ocufolin® for 6 months, and their imaging was performed at baseline, 4 months, and 6 months. The NC group was imaged once.ResultsBCVA and vascular indices of DR + PM patients at baseline were below those of NC and improved after Ocufolin® administration. Compared to baseline, DR + PM patients had significantly improved BCVA during the follow-up period (P < 0.05). RTP and arteriolar BFV were significantly increased at 6 months (P < 0.05), approaching NC.ConclusionOcufolin® may be effective in improving both visual acuity and retinal microcirculation in patients with DR + PM. Further studies with increasing sample size, and longer duration, including cases with severe DR, are needed.

Associations of MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) Polymorphisms with Susceptibility to Bladder Cancer: A Systematic Review and Meta-Analysis.

The effects of the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms on bladder cancer risk have been evaluated in some studies. However, the results were conflicting and ambiguous. Therefore, we aimed to perform a comprehensive meta-analysis to investigate the association of these polymorphisms with risk of bladder cancer from all eligible case-control studies. PubMed, Web of science, Scopus, SID, CNKI and SciELO databases were searched to identify all relevant studies published up to 1 January, 2021. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. A total of 20 case-control studies including 11 studies with 3463 cases and 3927 controls on MTHFR rs1801133 (677C>T) and 9 studies with 3177 cases and 3502 controls on rs180113 (1298A>C) polymorphism were selected. Pooled data revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were not associated with risk bladder cancer in overall. Stratified analysis by ethnicity revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were associated with bladder cancer risk in Asians, but not in Caucasians. There was no publication bias. The current meta-analysis revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were not risk factor for development of bladder cancer globally. However, large sample size, well-designed, and population-based studies should be performed to verify the association of the MTHFR polymorphisms with bladder cancer risk.

\u201cAssociation of MTHFR and MS/MTR gene polymorphisms with congenital heart defects in North Indian population (Jammu and Kashmir): a case\u2013control study encompassing meta-analysis and trial sequential analysis\u201d

BackgroundThe risk of Congenital Heart Defects (CHD) is greatly influenced by variants within the genes involved in folate-homocysteine metabolism. Polymorphism in MTHFR (C677T and G1793A) and MS/MTR (A2756G) genes increases the risk of developing CHD risk, but results are controversial. Therefore, we conducted a case–control association pilot study followed by an up-dated meta-analysis with trial sequential analysis (TSA) to obtain more precise estimate of the associations of these two gene variants with the CHD risk.MethodsFor case–control study, we enrolled 50 CHD patients and 100 unrelated healthy controls. Genotyping was done by PCR–RFLP method and meta-analysis was performed by MetaGenyo online Statistical Analysis System software. For meta-analysis total number of individuals was as follows: for MTHFR C677T 3450 CHD patients and 4447 controls whereas for MS A2756G 697 CHD patients and 777 controls.ResultsResults of the original pilot study suggested lack of association for MTHFR C677T and MS A2756G polymorphism with risk of CHD whereas MTHFR G1793A was significantly associated with the disease. On performing meta-analysis, a significant association was observed with MTHFR C677T polymorphism but not with MS A2756G. Trial sequential Analysis also confirmed the sufficient sample size requirement for findings of meta-analysis.ConclusionsThe results of the meta-analysis suggested a significant role of MTHFR in increased risk of CHD.