Methylenetetrahydrofolate Reductase Gene Research Articles

Juvenile rheumatoid arthritis in mono-zygotic twins

Aim: To describe the rate of juvenile idiopathic arthritis progression andto determine the degree of responsiveness to methotrexate and adalimmabmanagement in mono-zygotic twins with a methylene tetrahydrofolatereductase gene mutation.Methods: The study was a 5-month, twin concordance study. Thisincludes a retrospective study of medical records, activity and severity ofthe disease, complications, which included an objective clinical examinationof the patient, based on an assessment of the severity of the diseaseusing the disease activity score calculator for rheumatoid arthritis (DAS:28), liver function test, and folate cycle enzyme.Results: Based on the study conducted, mono-zygotic twins with the sameform of arthritis, which began at the same age with the same manifestationsyndrome and joint disease, combined with the same folate cyclemutation, with similar treatment regimen had different degrees of diseaseprogression and severity. The first twin had a complication of toxic hepatitisand a concomitant autoimmune thyroiditis. The second twin had amore serious progression with small joints ankylosis.Conclusion: The study shows that monozygotic twins with juvenile idiopathicarthritis with a similar defect in the folate cycle enzyme had differentrates of disease progression of varying severity and joint damage.Consequently, this requires further study in monozygotic twins with juvenilerheumatoid arthritis.

Association of genetic variants MTHFR A1298C and MTHFR C677T in the methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children with autism spectrum disorder

Association of genetic variants MTHFR A1298C and MTHFR C677T in the methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children with autism spectrum disorder

Prevalence of C677T single nucleotide polymorphism of methylene tetrahydrofolate reductase gene and its relationship with serum levels of homocysteine, vitamin B12, folate and cholesterol in Alzheimer’s patients

Prevalence of C677T single nucleotide polymorphism of methylene tetrahydrofolate reductase gene and its relationship with serum levels of homocysteine, vitamin B12, folate and cholesterol in Alzheimer’s patients

Post-COVID syndrome in patients with type 2 diabetes: definition, epidemiology, pathophysiology, biomarkers and genetic associations

The article presents the modern ideas about post-COVID syndrome, indicates various types and classifications of post-COVID syndrome, provides epidemiological data, including the patients with type 2 diabetes, also the definition of post-COVID syndrome is given. The group of patients defined as patients with post-COVID syndrome is very heterogeneous. Post-COVID syndrome is more common in the elderly, with comorbid pathology, severe disease. The pathophysiology of this syndrome in patients with type 2 diabetes mellitus is analyzed, and risk factors are indicated. The main biomarkers of disorders were determined: monocytes and their coefficients, acute phase proteins, some biochemical indicators, including analysis of genetic associations with the severity of post-COVID disorders (interferon gamma gene, methylenetetrahydrofolate reductase gene, ACE2 inhibitor). Genotyping of a sample of 26 single nucleotide polymorphisms in genes implicated in viral entry, immune response, and inflammation were significantly associated not only with the risk of long-term COVID-19 symptoms, but also with the cumulative incidence of post-COVID syndrome. Elevated levels of interleukin 6, C-reactive protein and tumor necrosis factor alpha may serve as potential diagnostic biomarkers in long-term COVID biomarkers of blood vascular transformation have great potential for diagnosis, and angiogenesis modulators may have therapeutic efficacy It has been shown that the vast majority of patients, in particular those suffering from type 2 diabetes, develop post-COVID-19 syndrome, and taking into account pre-existing diseases, post-COVID syndrome is not so harmless. By identifying common biomarkers and genetic associations, it is possible to identify the common molecular mechanism of post-COVID syndrome COVID-19 and diabetes mellitus. The novelty of disease association studies in the context of COVID-19 provides new insights into the management of rapidly evolving long-term COVID and post-COVID syndromes that have significant global implications.

Navigating thrombotic terrain: unveiling a novel homocystinuria mutation associated with thrombophilia in a 16 year old

BackgroundThrombophilia is characterised by an abnormality of blood coagulation that increases thrombosis. Homocystinuria encompasses a group of disorders marked by increased levels of homocysteine and other amino acids detectable in the bloodstream and urine. Conversely, homocystinuria due to methylenetetrahydrofolatereductase (MTHFR) deficiency, a rarer disorder, stems from impaired folate metabolism due to deficient MTHFR enzyme.Case presentationA 16-year-old boy presented with walking difficulties, headaches, and thrombotic events, thrombophilia workup led to a diagnosis of homocystinuria due to a novel mutation in MTHFR gene. Anticoagulant therapy was initiated which showed clinical improvement, but financial constraints hindered follow-up.ConclusionsThis case highlights the complexities of diagnosing and treating paediatric thrombophilia, particularly in resource-limited settings. Notably, the identified homozygous autosomal recessive (AR) missense variation in the MTHFR gene (Exon 4—c582C>G) represents a novel mutation, suggesting the ongoing significance of genetic research in elucidating the underlying mechanisms of thrombotic disorders.

COMBINATION OF TWO DIFFERENT C174T AND C235T OF THE ANGIOTENSINOGEN GENE MUTATION AND C677T METHYLENETETRAHYDROFOLATE REDUCTASE GENE MUTATION IN PATIENTS WITH CVD IN THE POPULATION OF AZERBAIJAN

We studied two mutations of C174T (Met174Tre) and C235T (Met235Tre) of the angiotensinogen gene and mutation C677T (Ala677Val) of the methylenetetrahydrofolate reductase gene, as well as their combinations among patients with cardiovascular diseases: coronary heart disease, myocardial infarction and hypertension, using a complex of modern molecular genetic diagnostic methods. A high frequency of these mutations has been established in the group of patients with severe forms of cardiovascular disorders. Homozygous and compound conditions were found in people with severe diseases. In particular, the heterozygous state of the mutation was found in people with moderate hypertension. It was also found that the presence of close blood relationship between the parents of patients with cardiovascular diseases increases the homozygotization of mutations of the genes AGT and MTGFR in probands. Consequently, such persons are susceptible to the disease or in other words, have an increased risk of developing diseases of the cardiovascular system. For the first time, the frequencies of these mutations in the Azerbaijani population have been determined, which are mostly consistent with the frequencies described in other populations of the world. The studied genetic markers are of interest as genes presumably associated with a wide range of cardiovascular diseases and can be used in further population and epidemiological studies. Therefore, the results of molecular genetic studies obtained by us in people with diseases of the cardiovascular system are of great practical importance. Timely prevention by detecting mutations of C174T, C235T of the AGT gene and C677T of the MTGFR gene in patients will allow doctors to carry out qualified treatment of cardiovascular diseases

The Influence of MTHFR C677T Variants on Neuropathy Risk Among T2dm Patients Receiving Monotherapy Metformin

Neuropathy is the most common microvascular complication among type 2 diabetes mellitus (T2DM). Metformin consumption increases neuropathy risk. The Methylenetetrahydrofolate reductase (MTHFR) enzyme has confirmed its role in neuropathy. Metformin and MTHFR could decrease folate and induce hyperhomoscysteine. One of the common variants of the MTHFR gene is C677T and its located in the exon area. This study aimed to observe the association between variant C677T in the MTHFR gene and the risk of neuropathy among newly diagnosed T2DM patients with naive metformin. This cross-sectional study recruited 103 patients. The neuropathy risk was examined according to medical judgment through Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS) criteria. Genotyping C677T was performed using PCR-RFLP. This study found only one patient has a homozygote mutant, but more than 50% of patients were detected with allele mutants. There were no statistical differences in patient characteristics between CC and CT genotypes (p>0.05). Association between C677T and neuropathy risk was not significant statistically, either in the genotype model (p=0.97), allele model (p=0.82), and dominant model (p=0.91). There was still no significant association after adjusting for several confounding factors. We conclude that C677T in our population did not influence neuropathy risk. More specific criteria and laboratory parameters indicated neuropathy should be examined in the future study.
 Keywords: MTHFR, neuropathy, metformin, and T2DM

[Analysis of 9 patients with adolescence-onset methylenetetrahydrofolate reductase deficiency].

Objective: To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency. Methods: This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively. Results: The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 μmol/L) was found in all patients, and decreased to 20-70 μmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders. Conclusions: Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

Diagnosis and treatment of venous thromboembolism during pregnancy relate to genetic polymorphism.

Previous research had shown that age, a positive family history, comorbidities, major surgical operations, gestation, and use of several medications could increase the incidence of venous thromboembolism (VTE). With the development of medical and clinical individualized treatment, many people exposed to above risk factors did not develop VTE, suggested that genetic factors are also involved in the development of VTE. In this review, we aim to summarize VTE diagnosis and treatment in pregnancy women related to gene polymorphism. A comprehensive electronic search using PubMed, MEDLINE, EMBASE and Web of Science was conducted to find relevant journal articles with key search terms including: "pregnancy OR pregnant," "venous thromboembolism OR VTE," "deep vein thrombosis OR DVT," "pulmonary embolism OR PE," and "genetic OR gene." Prominent publications from establishment of database till present were analysed to achieve a deeper understanding of VTE during pregnancy relate to genetic polymorphism, and the information was then collated to form this review. The literature review revealed that inherited thrombophilia significantly associated with the development of VTE, especially the factor V Leiden (FVL) and prothrombin gene mutation (PGM). Furthermore, the role of methylenetetrahydrofolate reductase (MTHFR) gene mutation in the development of pregnancy-related VTE remains controversial, further study is required. In the present study, Marburg I polymorphism (G511E), c.1538G>A and c.1601G>A in Factor V (FV), JAK2V617F mutation were reported as an independent risk factor for VTE, there is no sufficient evidence to confirm the gene mutation is related to VTE during pregnancy, these factors appearing as another promising potential diagnostic marker of VTE during pregnancy. Besides, the dosages of heparin in the treatment of VTE during pregnancy need be adjusted according to gene polymorphism of these population, particularly FVL or PGM carriers, and this area is not studied deeply, it is worth further study. Inherited thrombophilia significantly associated with the development of VTE, especially the FVL and PGM, however the relation between MTHFR gene mutation and pregnancy-related VTE remains controversial, further study is needed. In addition, the dosages of heparin in the treatment of VTE during pregnancy suggested to adjusted based on gene polymorphism in FVL and PGM, and establish better prediction models is a direction of future research.

Retrospective cohort study of the MTHFR C677T/A1298C polymorphisms and human homocysteine levels in Helicobacter pylori infection

This study avalited relationship between human Methylenetetrahydrofolate reductase (MTHFR) gene (C677T(rs1801133)/A1298C(rs1801131)) variants and homocysteine levels in 168 patients who are infected with Helicobacter pylori, diagnosed to PCR analysis. PCR-RFLP methods were performed to characterize the MTHFR gene C677T/A1298C variants in DNA samples obtained from gastric biopsies this patients. An immunoenzymatically assay was used for quantitative of total homocysteine and folate levels in the plasma of the same individuals. The adopted level statistical significance was to α = 0.05. The frequency of the C677T SNP was higher in infected individuals, wherein those with the CT/TT genotype presented a three-fold higher risk of acquiring Helicobacter pylori infection. The averages of the total homocysteine concentrations were associated with the TT genotype, advanced age and the male sex, but no dependence relationship was found with Helicobacter pylori infection.

Methylenetetrahydrofolate reductase levels and gene expression in leukemia

Abstract Leukemia is a neoplastic disease that affects the proliferation of white blood cells and their progenitors. Folic acid deficiency is well-known as a risk factor for leukemia. Methylenetetrahydrofolate reductase (MTHFR) enzyme functions in the folate metabolism route, DNA synthesis and methylation processes. Numerous research has been conducted to investigate the link between MTHFR and several human illnesses, including cancer, cardiovascular disease, psychiatric disorders and neurological issues. The current study aimed to examine MTHFR levels and gene expression in patients with leukemia. The research was carried out between February and October of 2022. There were 130 subjects in total, 80 with leukemia, 45 with AML (Female = 16, Male = 26) with a mean age of (32.32±2.69), and 35 with ALL (Female = 16, Male = 19) with a mean age of (35.794±0.63). The study included 50 healthy subjects as a healthy control group (Female = 28, Male = 22), with an average age of (41.8±1.57) years. MTHFR and Folic acid were measured using ELISA, while MTHFR mRNA was assessed using qPCR in blood and plasma. Folic acid and MTHFR levels were found to be lower in patients with AML and ALL compared to controls (p <0.01). MTHFR gene expression was found to be downregulated in leukemia patients (p <0.01). The findings of the study give support for future research into the effect of folic acid level and supplementation on leukemia-associated pathological outcomes. Folic acid deficiency may affect the folate mediate-one carbon metabolism pathway, as evidenced by changes in the expression of the mRNA MTHFR gene. As a result, more research into the effects of folate status and folic acid supplementation on leukemia is needed to investigate potential therapeutic strategies.

Interaction effects of MTHFR C677T and A1298C polymorphisms with maternal glycated haemoglobin levels on adverse birth outcomes.

The role of maternal genetic factors in the association between high glycated haemoglobin (HbA1c) levels and adverse birth outcomes remains unclear. In this study, the maternal HbA1c levels of 5108 normoglycemic pregnant women in China were measured, and A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were genotyped. Elevated HbA1c levels during the second trimester were associated with increased risks of macrosomia, large-for-gestational age (LGA), preterm birth (PTB), and reduced gestational age (p<0.05). Pregnant women with MTHFR A1298C AA or C677T CT+TT genotypes were susceptible to adverse pregnancy outcomes related to HbA1c levels. Among pregnant women with the A1298C AA genotype, each standard deviation (SD) increase in HbA1c levels increased the risk of PTB by 1.32-times and reduced the gestational age by 0.11weeks (p<0.05). For MTHFR C677T CC+TT genotype carriers, higher HbA1c levels were associated with 1.49-, 1.24-, and 1.23-times increased risks of macrosomia, LGA, and PTB, respectively (p<0.05). A U-shaped curve for PTB risk in relation to HbA1c levels was observed among the C677T CC+TT participants, with a cut-off value of 4.58%. Among subjects with the A1298C AA genotype combined with the C677T CT+TT genotype, each SD increase in HbA1c levels was associated with 1.40 and 1.37-times increased risks of LGA and PTB, respectively. Our findings highlight the importance of glycaemic control during pregnancy and the potential impact of genetic factors on birth outcomes. However, further large-scale studies are required to confirm these findings.

Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage

BackgroundInherited thrombophilia (IT) has a complex pathophysiology and is associated with recurrent miscarriage (RM) by causing placental insufficiency and inhibiting fetal development. However, thrombophilia screening in unexplained RM cases is still questionable. This study aimed to investigate the association between the common eight IT mutations and their combinations among Palestinian women with unexplained RM.MethodsThis is an unmatched case-control study with 200 women (100 unexplained RM cases, 100 controls). Eight common IT mutations namely Factor V Leiden (FVL), prothrombin gene (FII) G202120A, Methylenetetrahydrofolate Reductase (MTHFR) gene (C677T and A1298C), B-fibrinogen gene − 455G > A, FV HR2 A4070G, Plasminogen activator inhibitor 1 (PAI1) 5G/4G and Factor XIIIA (FXIIIA) V34L; were analyzed. The first five mutations were analyzed by Restriction Fragment Length Polymorphism PCR and the other three mutations were analyzed using Amplification Refractory Mutation System PCR.ResultsThe prevalence of the eight IT mutations among the control group was in the order PAI1 5G/4G (69%), MTHFR C677T (53%) and A1298C (47%), BFG − 455G > A (35%), FVL and FV HR2 (each 18%), FXIIIA V34L (16%) and FII G20210A (3%). Patients had a higher percentage of MTHFR A1298C (heterozygotes and mutant homozygote) compared to controls (p = 0.016). Frequencies of mutant alleles MTHFR A1298C (p < 0.001) and FXIIIA V34L (p = 0.009) were higher among patients compared to controls. No significant differences were observed for all other mutations or mutant alleles. Most patients (75%) and controls (75%) have 2–4 mutant alleles out of 8 mutant alleles studied, while 1% of patients and 2% of controls have zero mutant alleles. None of the combinations of the most often studied mutations (FVL, FII G20210A, MTHFR C1677T, and MTHFR A1298C) showed a significant difference between patients and controls.ConclusionsThere was a significant association between unexplained RM and the mutant alleles of MTHFR A1298C and FXIIIA V34L. No significant association was observed between unexplained RM and the combination of both mutant alleles for the mutations studied. This study is the first Palestinian report that evaluates eight inherited thrombophilia mutations and their alleles’ combinations in unexplained RM cases.

Hemicentral retinal vein occlusion in a patient with a history of coronavirus disease 2019 infection: a case report and review of the literature

BackgroundConsidering the various manifestations of coronavirus disease 2019 and its imperative importance in terms of the right clinical approach and early management, we sought to present a hemicentral retinal vein occlusion case, with a history of heterozygosity of methylenetetrahydrofolate reductase (MTHFR) genes and potential for clotting complications as a late manifestation of coronavirus disease 2019, and provide a brief review of reported retinal vein occlusion cases in patients with coronavirus disease 2019.Case presentationA 35-year-old Iranian patient presented with a visual impairment in the left eye 4 months after recovering from coronavirus disease 2019. He reported a mild blurring of vision in the same eye a few days after admission due to coronavirus disease 2019. The ophthalmic evaluation was compatible with hemicentral retinal vein occlusion. Systemic and laboratory workups were negative except for borderline protein C activity, homocysteine levels, and heterozygosity of MTHFR genes. The patient was scheduled to receive three monthly intravitreal antivascular endothelial growth factor injections.ConclusionWe present a case of inferior hemicentral retinal vein occlusion case with an MTHFR mutation with sequential loss of vision 4 months after coronavirus disease 2019 to make clinicians aware of the possibility of late ocular coronavirus disease 2019 manifestations.

Congenital septal defects in Karachi, Pakistan: an update of mutational screening by high-resolution melting (HRM) analysis of MTHFR C677T

BackgroundCongenital heart defects (CHDs) are the heart structural malformations present at birth. Septal defects account for 40% of CHD, including atrial, ventricular and atrioventricular septal defects. In Pakistan, the prevalence of CHD is 3.4 in 1000, and a study estimated that 60,000 babies are born with CHD annually. Methylenetetrahydrofolate reductase (MTHFR), a chief enzyme, involved in the folate metabolism. The missense mutation, C677T (rs1801133), exists in MTHFR gene, results in a MTHFR thermolabile variant having low enzymatic activity. The study is aim to identify the MTHFR C677T variant association with septal defects.MethodsSamples of 194 CHD patients (age X¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\overline{X }\\hspace{0.17em}$$\\end{document}= 5.8 ± 5.1) and 50 normal echo controls (age X¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\overline{X }\\hspace{0.17em}$$\\end{document}= 6.0 ± 4.9), confirmed by pediatric consultant, were collected. Extracted DNA, quantified by agarose gel electrophoresis and nanodrop, was screened for SNP by high-resolution melting (HRM). Further, HRM results were confirmed using restriction analysis and sequencing. HRM was simply and precisely genotyped the samples within 3 h at low cost.ResultsGenotypic data suggested that heterozygous mutant (CT) was frequent in congenital septal defect patients (0.26) which was higher than controls (0.143), p > 0.05. Mutant (TT) genotype was not found in this study.Conclusionsrs1801133 has lack of significant association with congenital septal defects. The absence of TT genotype in this study suggesting the role of natural selection in targeted population. HRM is an easy, fast and next generation of PCR, which may be used for applied genomics.

Association Study of Polymorphisms in Folate Metabolism and Mothers of Down Syndrome Offsprings in the Southwest of Iran

Background: Down syndrome (DS) is a complex genetic disease that is caused by having three copies of chromosome 21. A possible association between polymorphisms in maternal folate metabolism genes and DS has been evaluated. Objectives: It was aimed to first investigate the influence of C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and plasma homocysteine (Hcy) on the maternal risk for DS in the southwest of Iran. Methods: The MTHFR C677T and A1298C polymorphisms were genotyped using restriction fragment length polymorphism and Sanger sequencing, respectively. Allele and genotype frequencies and the dominant model of the MTHFR C677T and A1298C polymorphisms were evaluated in 80 mothers of children with DS and 80 control mothers. Eventually, the ELISA test was used to compare the concentration of plasma Hcy in both groups. Results: A significant association was observed in the 677T and 1298C alleles between the mothers of DS and control groups (P = 0.00077 and P = 0.01248, respectively). Further, the median concentrations of Hcy were significantly higher in mothers with DS babies compared to the control group (P &lt; 0.05). Conclusions: There was an association between MTHFR C677T, A1298C, and plasma Hcy concentrations as the maternal risk of mothers with DS children.

Coronary Artery Disease Is Related to Methylation Disorders Caused by the c.1286A&gt;C MTHFR Polymorphism and to Low Serum 5-MTHF and Folic Acid Concentrations—Preliminary Results

Background: Single nucleotide polymorphisms in gene encoding is the key enzyme in the folates pathway, methyltetrahydrofolate reductase (MTHFR), which causes methylation disorders associated with coronary artery disease (CAD). We evaluated associations between methylation disorders caused by MTHFR gene polymorphisms and the blood folate concentrations (folic acid, 5-MTHF) in CAD patients. Methods: Study group: 34 patients with CAD confirmed by invasive coronary angiography (ICA). Controls: 14 patients without CAD symptoms or significant coronary artery stenosis, based on ICA or multislice computed tomography (MSCT) with coronary artery calcification (CAC) scoring. Real-time PCR genotyping was assessed using TaqMan™ probes. Folic acid and 5-MTHF concentrations in blood serum were determined using Liquid Chromatography-Mass Spectrometry (LC-MS). Results: The c.[1286A&gt;C];[1286A&gt;C] MTHFR polymorphism occurred significantly more often in (CAD+) patients compared to the (CAD−) cohort and to the selected general European “CEU_GENO_PANEL” population sample. The concentration of 5-MTHF and folic acid in subgroups of CAD+ patients with methylation disorders categorized by genotypes and CAD presence (CAD+) was always lower in CAD+ subgroups compared to non-CAD individuals (CAD−). Conclusions: Further studies on a larger scale are needed to implicate the homozygous c.1286A&gt;C MTHFR variant as CAD genetic marker and the 5-MTHF as CAD biomarker. Identification of high CAD risk using genetic and phenotypic tests can contribute to personalized therapy using an active (methylated) form of folic acid (5-MTHF) in CAD patients with MTHFR polymorphisms.

Methylenetetrahydrofolate reductase polymorphic variants C677T and A1298C in rectal cancer in Slavic population: significance for cancer risk and response to chemoradiotherapy.

Background: Methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNPs) have been suggested as risk, prognostic, and predictive factors for colorectal cancer in various populations, but have not been validated so far. The aim of this study was to examine the association of MTHFR C677T (rs1801133) and A1298C (rs1801131) single nucleotide polymorphisms with the risk of rectal cancer as well as the response to neoadjuvant chemoradiotherapy (nCRT) based on 5-Fluorouracil (5-FU)/leucovorin (LV) in the locally advanced setting. Patients and methods: This case-control study included 119 healthy controls and 97 patients with locally advanced rectal cancer (LARC). For MTHFR genotyping, restriction fragment length polymorphism analysis (PCR-RFLP) was employed. Results: In silico analysis highlighted that SNPs C677T and A1298T correlate with MTHFR gene expression, and that gene expression profile correlates with cancer risk and stage. Using dominant and recessive models, it was found that the MTHFR 677CC vs. 677CT+677TT have increased risk of cancer development (odds ratio (OR): 2.27; 95% confidence interval (CI): 1.30-3.95, p = 0.002) as well as 677CC+677CT compared to 677TT (OR: 4.18, 95% CI: 1.16-14.99, p = 0.014). MTHFR 1298AA also shown increased risk for cancer development compared to 1298AC+1298CC (OR:2.0, 95% CI: 1.20-3.59, p = 0.035) Statistical analysis of combined genotypes highlighted the protective role of CT/AC combined genotype (OR: 3.15 95% CI: 1.576-6.279, p = 0.002) while the CC/AA genotype showed an increased risk for rectal cancer development (OR: 2.499, 95% CI: 1.246-5.081, p = 0.016) The carriers of the 677C/1298A haplotype had the highest risk for developing rectal cancer (OR: 1.74; 95% CI: 1.198-2.530, p = 0.002) while the 677T/1298C haplotype seems to provide a protective effect. (OR: 0.44; 95%CI 0.248-0.795, p = 0.003). No significant association with response to chemoradiotherapy was found. Conclusion: Our data point to MTHFR 667C allele and 1298A alleles as low-penetrance risk factors for rectal cancer in our population. To the best of our knowledge, this is the first study of this type performed on the Slavic population in the Western Balkan, as various population-based factors might also be significant our findings can be used for future meta-analyses and the construction of genetic cancer risk prediction panels.

The Role of Sociogenomics on Chronic Wounds 

Background and Objective: &#x0D; Chronic wounds affect almost 2.5% of the United States population. Along with substantial healthcare costs, other factors like reduced employment opportunities and social isolation further complicate the patient’s quality of life. Socioeconomic status (SES) has been shown to influence gene expression that can increase susceptibility and deterioration of chronic wounds. Our study looks to identify genes that have been impacted by SES in chronic wound patients. Exploring this association can enhance understanding of the relationship between SES and chronic wound outcomes. &#x0D; Experimental Design: &#x0D; A cohort of 72 chronic wound patients were recruited. Patient demographics and socioeconomic backgrounds were collected. Blood DNA isolation was performed and allotted for genetic analysis by Axiom™ Precision Medicine Diversity Array (PMDA). DNA genotyping data was obtained, and single nucleotide polymorphisms (SNP) markers pertaining to wound healing were studied. P &lt; 0.05 were used to designate significant SNP marker mutations in the cohort. &#x0D; Results: &#x0D; To add strength to our project, we have chosen to further study the results obtained by our group (https://doi.org/10.18060/27205), which has previously found significant SNPs associations of the vitamin D receptor (VDR) and the methylenetetrahydrofolate reductase (MTHFR) genes in chronic wound patients. Using PMDA, our analysis showed polymorphisms in CYP24A1 (p = 0.0072), a gene involved in vitamin D metabolism, and MTHFR (p = 0.00625), a gene involved in folate and homocysteine metabolism. Modifications of these genes have been associated with pathogenesis to impaired wound healing. &#x0D; Conclusion: &#x0D; There is a need for further investigation into health outcomes and their association with SES. Our study aims to address the knowledge gap in this field by focusing on chronic wound healing in relation to socioeconomic status. With our results, we hope to emphasize the importance of sociogenomics, and how it can be utilized to advocate for improved patient outcomes across all socioeconomic backgrounds. &#x0D;  &#x0D; Acknowledgements: &#x0D; This project was funded, in part, with support from the Indiana Clinical and Translational Sciences Institute funded, in part by UL1TR002529 from the National Institutes of Health (NIH). The presented work is also supported by NIH grants R01DK135447 and R01DK128845 to CKS. The laboratory of KS is supported by DoD grant W81XWH-22-1-0146. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.  

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

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