The distribution of allelic variants of folate metabolism genes in the world’s populations varies significantly depending on ethnicity and geographical area of residence. According to a number of studies, the presence of polymorphism in folate cycle genes may be associated with various pathological conditions, including diseases of the cardiovascular system and complications of the physiological course of pregnancy. However, there are studies that do not show the presence of a relationship between the carriage of minor folate cycle gene alleles with cardiovascular pathology and a burdened obstetric history. The purpose of the study was to analyze the spread of allelic variants of folate metabolism genes, their relationship with cardiovascular pathology and complications of pregnancy. Materials and methods. The study included 2.672 people. All participants underwent real-time molecular genetic examination of folate cycle genes by PCR. The analysis of the distribution of folate cycle gene alleles in the population of the Arkhangelsk region was carried out and the presence of a correlation between the carriage of alleles with low functional activity with cardiovascular pathology and a burdened obstetric history was assessed. Results. The carriage of minor alleles of folate metabolism genes in the study sample is presented as follows: the frequency of the T allele of the MTHFR C677T gene (rs1801133) is 28.8%, the C allele of the MTHFR A1298C gene (rs1801131) is 33.1%, the G allele of the MTR A2756G gene (rs1805087) is 24.1%, the G allele The MTRR A66G gene (rs1801394) is 56.2%. There were no significant differences in the frequency of carriage of minor allelic variants of folate cycle genes between healthy volunteers and RCATT patients. Conclusion. In the studied sample, the carriage of low-functional allelic variants of genes encoding folate cycle enzymes was not associated with cardiovascular diseases and a burdened obstetric history.

Arterial hypertension (AH) is an important risk factor for cardiovascular diseases, a group of diseases that constitutes the most frequent cause of death worldwide. Most AH patients globally are diagnosed with essential hypertension (EH), since they do not present an identifiable cause for high blood pressure (HBP). The aim of this study was to assess the associations between EH and genetic variants MTHFR C677T, ACE I/D, AT1R A1166C and eNOS 4a/b in the adult Caucasian population of Romania. Methods: A case–control study was conducted including 845 EH patients and 845 controls. Clinical, para-clinical and lifestyle data were collected from each patient, as well as blood samples for genotyping the polymorphisms of four candidate genes for EH—MTHFR C677T (rs1801133), ACE I/D (rs4646994), AT1R A1166C (rs5186) and eNOS 4a/b—using PCR-based methods. Results: EH was associated with both genetic and environmental factors. Carriers of ACE DD and MTHFR TT genotypes presented an increased risk for EH (ACE DD: OR = 1.44, p = 0.0007; MTHFR TT: OR = 1.46, p = 0.0007). Lifestyle (smoking, physical activity) aspects were associated with EH. The risk of EH increased when both polymorphisms were associated with smoking (ACE DD: OR = 1.62, p = 0.0005; MTHFR TT: OR = 1.68, p = 0.0004). Conclusions: Our findings indicate that ACE I/D and MTHFR C677T may play a role in EH susceptibility, whereas polymorphisms AT1R A1166C and eNOS 4a/b do not appear to be associated. Furthermore, the interaction between genetic factors (ACE I/D, MTHFR C677T) and lifestyle factors such as smoking suggests an increased risk for developing essential hypertension.

Hyperhomocysteinemia and oxidative stress are increasingly recognized in pediatric malignancies, but their interplay remains unclear. We evaluated homocysteine metabolism, vitamin cofactor status, and oxidative stress in 90 children with newly diagnosed lymphoma before chemotherapy. Plasma homocysteine, folate, vitamins B12 and B6, and oxidative stress markers (8-OHdG, nitrotyrosine, protein carbonyls, NO, iNOS) were measured, alongside MTHFR C677T genotyping. Hyperhomocysteinemia (>15 μmol/L) was present in 96% (n = 87), with low folate (median 2.6 ng/mL) and B12 deficiency (B12<200 pg/mL in 84%, n = 76). Homocysteine correlated inversely with folate and B6, and positively with 8-OHdG (p < 0.05). MTHFR 677CT carriers had markedly elevated nitrotyrosine and higher 8-OHdG (p < 0.05), independent of homocysteine levels. In multivariate analysis, the T-allele predicted nitrotyrosine (p < 0.05), while homocysteine did not. These findings demonstrate profound disruption of one-carbon metabolism and oxidative stress in pediatric lymphoma at diagnosis, with genetic and micronutrient factors modulating the oxidative burden, emphasizing the value of early metabolic assessment.

Background: Klinefelter syndrome (KS), the most common sex chromosome aneuploidy in males (47,XXY), is generally associated with hypogonadism, gynecomastia, and infertility. Nevertheless, its association with thrombotic risk remains insufficiently recognized, despite accumulating evidence indicating a predisposition to venous thromboembolism (VTE) comparable to that observed in classical, inherited thrombophilias. Description of Case: We present the case of a 33-year-old South Asian male who exhibited unilateral lower limb swelling and pain persisting for one month. Doppler ultrasonography revealed chronic deep vein thrombosis (DVT) affecting the left common femoral and deep femoral veins. The patient lacked identifiable risk factors for thrombosis, such as recent surgery, trauma, malignancy, or immobilization. Physical examination revealed signs of hypogonadism and gynecomastia. Hormonal assays indicated elevated gonadotropin levels with low serum testosterone levels, while karyotype analysis confirmed a 47,XXY genotype, consistent with KS. Further evaluations, including screening for acquired thrombophilias (antiphospholipid antibodies) and genetic mutations (Factor V Leiden, Prothrombin G20210A, and MTHFR C677T), yielded negative results. The patient was successfully managed with heparin, transitioned to long-term anticoagulation with warfarin, and demonstrated clinical improvement upon follow-up. Discussion: This case highlights the significant yet often overlooked association between KS and thrombotic events. The pathophysiological mechanisms remain unclear but are hypothesized to be multifactorial, involving increased expression of X-linked coagulation factors (e.g., Factor VIII), endothelial dysfunction, and a higher prevalence of comorbidities. Notably, in our case, the absence of conventional or inherited prothrombotic factors underscores KS as a potential primary contributor to the hypercoagulable state. Conclusion: Clinicians are advised to maintain a heightened level of suspicion for KS in male patients who present with unexplained thrombotic events, particularly when these events are accompanied by symptoms indicative of hypogonadism. The early identification and management of thrombotic risk in individuals with KS are crucial to mitigating morbidity. Further research is necessary to elucidate the mechanisms that link KS with thrombophilia, as this may inform screening strategies and therapeutic interventions.

Background and Objectives: Thrombophilia is a prothrombotic disorder that increases the risk of blood clotting and can pose serious health problems. It is considered a condition of gene–gene or gene–environment interactions. Variation in the prevalence of thrombophilia mutations and their interaction among populations necessitates localized genetic assessments. However, population-based genetic data remains limited for developing effective preventive strategies. Materials and Methods: This cross-sectional observational study was conducted over five years (2020–2024) at a tertiary university hospital in Northern Greece. A total of 2961 individuals aged 18–85 years (mean: 50.5) were registered based on family or medical history of venous thromboembolism (VTE) or clinical symptoms of VTE. The final analysis included 2078 participants comprising 1143 males (55%) and 935 females (45%), who met all the inclusion criteria. Inclusion criteria were absence of acute illness or malignancy, informed consent, and an adequate DNA quantity for genotyping, whereas excluded criteria included incomplete laboratory data, active inflammatory or malignant disease, and cognitive or psychiatric conditions. Peripheral blood samples were collected in 2 mL K3-EDTA tubes, and genomic DNA was analyzed using real-time polymerase chain reaction (PCR) with melting curve analysis and hybridization probes (LightMix® in vitro diagnostics, TIB MolBiol, Berlin, Germany). Five thrombophilia-related polymorphisms, Factor V Leiden (F5 G1691A), prothrombin (F2 G20210A), methylenetetrahydrofolate reductase (MTHFR C677T and MTHFR A1298C), and Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G, were examined for allele and genotype frequencies, Hardy–Weinberg equilibrium testing, pairwise linkage disequilibrium (D′ and r2), and power analysis. For subjects tested for Factor V Leiden (n = 1476), the activated protein C resistance (APC) ratio was additionally evaluated using the ACL TOP 750 analyzer. Results: Allele frequencies were 7.3% for FV Leiden and 3.7% for FII. The PAI-1 allele was distributed at 44%, while the MTHFR (C677T and A1298C) alleles were each present at 33%. Significant linkage disequilibrium was identified between MTHFR (C677T and A1298C) and between MTHFR A1298C and PAI-1. No evolutionary pressure or demographic bias was found in the Hardy–Weinberg equilibrium. The APC ratio demonstrated a high sensitivity (99.2%) and specificity (96.6%), indicating that it may serve as a reliable screening method. Conclusions: Our findings highlight informative patterns in the genetic predisposition to thrombophilia, which may help develop rule-based strategies for implementing thromboprophylaxis guidelines and personalized medical interventions.

Calciphylaxis is a rare, life-threatening complication in dialysis patients, characterized by necrotic skin lesions and often linked to mineral metabolism disorders and proinflammatory states. We report a 42-year-old female with lupus nephritis on long-term hemodialysis (HD) who developed calciphylaxis after kidney transplantation complicated by acute rejection, vascular thrombosis, and surgical infection. She presented with necrotic skin ulcers, elevated inflammatory markers (ESR 96 mm/h, CRP up to 10 mg/dL), and a heterozygous MTHFR C677T mutation. Eight double-filtration plasmapheresis (DFPP) sessions over 3 months using an EC-50W filter achieved CRP (−49%) and fibrinogen (−69%) reduction, with lesion improvement. Post-session leukocyte rebound (+205%) suggested microcirculatory recovery. At treatment completion, her condition stabilized without further flare-ups. DFPP may be a valuable option for refractory calciphylaxis with persistent inflammation.

Disclosure: K. Komisarenko: None.Background: T2DM is a multifactorial metabolic disease with significant genetic contributions. Polymorphisms in folate metabolism genes, particularly MTHFR C677T and A1298C, are associated with impaired homocysteine clearance, endothelial dysfunction, and neurotransmitter imbalance. Post-COVID metabolic stress may amplify these effects, especially in individuals with T2DM, but the combined influence of clinical and genetic factors remains poorly defined. Objective: To evaluate the association of MTHFR C677T and A1298C polymorphisms with plasma levels of serotonin, ST-2, and homocysteine in post-COVID T2DM and to develop multivariate regression models for predicting biomarker variations based on genetic and clinical profiles. Methods: This study included 250 adults with previously diagnosed T2DM who had recovered from confirmed SARS-CoV-2 infection. Demographic and clinical data, including BMI, hypertension status, and COVID-19 treatment modalities, were collected. MTHFR genotyping was performed using PCR-RFLP. Plasma levels of homocysteine were quantified via LC-MS/MS, while serotonin and ST-2 were measured using ELISA. Predictive models were constructed through multiple linear regression. Statistical significance was set at p < 0.05. Results: Patients carrying the 677T or 1298C alleles had significantly higher homocysteine (+3 µmol/L; p < 0.01) and lower serotonin levels (p < 0.05) than wild-type individuals. Elevated BMI and hypertension were additional predictors of unfavorable biomarker changes. Age was negatively associated with ST-2 levels, while a history of pulmonary insufficiency predicted increased ST-2 (p < 0.05). Dexamethasone treatment during COVID-19 was linked to increased serotonin, and oxygen therapy to reduced ST-2. All models were statistically significant (ANOVA p < 0.001) with strong explanatory power (R² = 0.87-0.91). Conclusions:MTHFR gene variants, in conjunction with clinical variables such as BMI and hypertension, influence key biochemical markers in post-COVID T2DM. Integrating genetic and metabolic profiling may inform individualized strategies for folate supplementation and cardiometabolic control. These findings support the practical implementation of genetic screening and biomarker monitoring in post-COVID endocrine care to reduce vascular, neuropsychiatric, and inflammatory complications in high-risk diabetic patients.Presentation: Saturday, July 12, 2025

Background: Patient managment with high thrombotic risk on both arterial and venous espury, united with bleeding risk, remains as complex as possible to evaluate in clinical practice. We can think about what the correct therapeutic choise is to safeguard the patient on the arterial and venous side. Methods: Man of 66 years old arrives to optimize his drug therapy. He has a heterozygosis mutation of MTHFR C677T gene and the PAI I 4G/5G gene. Although in genotype not particulary predisposing to thrombotic risk, his medical history reports a subocclusive thrombosis of the splenic vein with intraparenchymal involvement in the 2024, treated with EBPM at the dosage of 6000 UI every 12 hours for about three months, then replaced by Edoxaban at the dosage of 60 mg every 24 hours. During this treatment, the patient has an ischemic accident in the subcortical cortical site in January 2025, following this, the patient interrupts the therapy with edoxaban and starts an anti platelet therapy with Clopidogrel and acetyl salicylic acid ad at the dosage respectively of 75 mg and 100 mg every 24 hours. The patient carries out this more aggressive therapy for a few months, subsequently it is decided to switch to only acetyl salicily acyd at the dosage of 75 mg every 24 hours and to reintroduce edoxaban at the dosage of 60 mg every 24 hours. However, the patient also has a pronunced hemorrhagic phenotype die his metabolic liver disease complicated by portal hypertension and from the presence of gastric varicose veins of degree IGVI, condition in itself with potential bleeding risk. In addition to a recent colonoscopy active bleeding was detected in the intestinal diverticulums. Results: Since there is a marked bleeding risk in the face of the overt thrombotic risk, we procedeed to reconfirm the therapy with acid acetylsalicylic a dose of 75 mg once a day, it is then decided ti replace edoxaban with apixaban at the dose of 2.5 mg twice a day. We proceed with this decision in the face of the numerous studies that prove the lower bleeding risk in the use of Apixaban compared to other DOACs. Conclusions: At follow up carried out after 4 weeks, no bleeding was detected, stable blood chemical values, the patient also performs a virtual colonoscopy resulting in a negative result of acuteness, the thrombotic outcome in the splenic vein remains sographically stable.

BACKGROUNDFolate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder (ASD). However, most studies have primarily used single candidate gene typing strategies (such as targeted polymerase chain reaction technology), and current findings remain inconsistent.AIMTo investigate the association of folate metabolism gene polymorphisms with ASD susceptibility and symptom severity among Chinese children.METHODSWhole-exome sequencing (WES) was conducted to systematically screen for coding region variants of key genes in the folate metabolism pathway among children with ASD, focusing on identifying polymorphisms with high mutation frequencies and potential pathogenic effects. A case-control study was then conducted to explore the association of candidate folate metabolism gene polymorphisms with the susceptibility and severity of ASD.RESULTSWES was performed on 70 children with ASD, and the case-control study included 170 children with ASD and 170 healthy controls. WES revealed that 84.3% (59/70) of children with ASD carried potentially pathogenic variants enriched in folate metabolism pathways. MTHFR C677T and MTRR A66G were significantly associated with an increased risk of ASD in both codominant and dominant models (P < 0.05). The dominant model of MTRR A66G was also significantly associated with higher scores in the domains of social relations, body and object use, social and adaptive skills, total scores on the Autism Behavior Checklist, as well as emotional reactivity, nonverbal communication, and activity level on the Childhood Autism Rating Scale (P < 0.05).CONCLUSIONMost children with ASD carry deleterious variants in folate metabolism-related pathways. MTHFR C677T and MTRR A66G mutations are significantly associated with ASD.

Novel Genetic Susceptibility Markers for Breast Cancer in Iraqi Women: First Evidence of CYP3A4*1B Protective Effects and GSTP1/MTHFR Risk Associations.

Gestational diabetes mellitus (GDM) is a common pregnancy complication with rising incidence and adverse maternal-fetal outcomes. Genetic polymorphisms in folate metabolism genes may influence GDM susceptibility through homocysteine pathway alterations. To investigate the associations between MTHFR (C677T, A1298C) and MTRR (A66G) polymorphisms and GDM risk, including gene‒gene interactions, in Chinese Han pregnant women, this retrospective cohort study analyzed 1312 Chinese Han pregnant women. The MTHFR C677T, A1298C, and MTRR A66G polymorphisms were genotyped using allele-specific PCR. Polymorphism-GDM associations were assessed using logistic regression, adjusting for maternal age, prepregnancy BMI, and folate intake. Gene‒gene interactions were evaluated using multiplicative interaction models. After confounder adjustment, the MTHFR 677TT genotype was associated with GDM (OR 1.89, 95% CI 1.24−2.93) compared to wild-type. The MTRR 66AG and 66GG genotypes were associated with GDM, with ORs of 2.73 (95% CI: 1.93–3.89) and 3.10 (95% CI: 1.72–5.41), respectively. Significant gene‒gene interactions were observed between MTHFR C677T & A1298C (OR 2.22, 95% CI 1.25−4.23 for TT/AA combination) and MTHFR C677T & MTRR A66G (OR 6.06, 95% CI 3.48−14.10 for TT/AG combination), indicating synergistic effects that surpass the expected multiplicative combination of individual polymorphism effects. MTHFR C677T and MTRR A66G polymorphisms independently and interactively increase GDM odds in Chinese Han women, enabling personalized risk prediction and targeted prevention.

Clinical and genetic profiling of fibromyalgia-associated dry eye: A multifactorial approach.

Abstract Background Recurrent spontaneous abortion (RSA) refers to the occurrence of two or more consecutive pregnancy losses before 20 weeks of gestation. According to Ministry of Health and Family Welfare, Govt. of India, the prevalence of RSA is approximately 7.4% in Indian women. Several factors, such as epidemiological, genetic and anatomical, are involved in the pathogenesis of RSA. MTHFR gene is involved in folate metabolism, and mutation of this gene in 677 position increases the risk of venous thromboembolism. While VDR gene is mainly responsible for implantation and maturation of fetus, low expression of VDR gene is associated with pregnancy complications, preeclampsia and gestational diabetes mellitus (GDM). Materials and Methods A total of 110 study participants (55 RSA patients and 55 control subjects) were recruited for this case-control study. Genotyping of MTHFR C677T (rs1801133) and VDR C &gt; T (rs2228570) gene variants was done by PCR–RFLP method. χ2 test and odds ratio with 95% CI were calculated to determine the strength of association of genetic variants with RSA. Bonferroni corrected p value &lt; 0.05 was considered as statistically significant. Results The findings revealed that T allele of MTHFR C677T (rs1801133) variant increases RSA risk (OR—2.494, 95%CI—1.08 to 5.756, p value–0.046) in our study population. There was a lack of association between VDR gene C &gt; T (rs2228570) variant and RSA risk and/or protection. Conclusion The finding of the study demonstrates a significant association of T allele of MTHFR C677T (rs1801133) variant with susceptibility to RSA in our study population.

Background: Inherited thrombophilia is increasingly recognized as a contributing factor to placental vascular pathology and adverse pregnancy outcomes. While the clinical implications are well-established, fewer studies have systematically explored the histopathological changes associated with specific genetic mutations in thrombophilic pregnancies. Materials and Methods: This retrospective observational study included two cohorts of placental samples collected between September 2020 and September 2024 at a tertiary maternity hospital. Group 1 included women diagnosed with hereditary thrombophilia, and Group 2 served as controls without known maternal pathology. Placentas were examined macroscopically and histologically, with pathologists blinded to group allocation. Histological lesions were classified according to the Amsterdam Consensus and quantified using a composite score (0–5) based on five key vascular features. Results: Placental lesions associated with maternal vascular malperfusion—including infarctions, intervillous thrombosis, stromal fibrosis, villous stasis, and acute atherosis—were significantly more frequent in the thrombophilia group (p < 0.05 for most lesions). A combination of well-established thrombophilic mutations (Factor V Leiden, Prothrombin G20210A) and other genetic polymorphisms with uncertain clinical relevance (MTHFR C677T, PAI-1 4G/4G) showed moderate-to-strong correlations with histopathological markers of placental vascular injury. A composite histological score ≥3 was significantly associated with thrombophilia (p < 0.001). Umbilical cord abnormalities, particularly altered coiling and hypertwisting, were also more prevalent in thrombophilic cases. Conclusions: Thrombophilia is associated with distinct and quantifiable placental vascular lesions, even in pregnancies without overt clinical complications. The use of a histological scoring system may aid in the retrospective identification of thrombophilia-related placental pathology and support the integration of genetic and histologic data in perinatal risk assessment.

In this research, we seek to understand the evolutionary forces which have resulted in the distribution of the MTHFR C677T single nucleotide polymorphism, which is associated with fertility-related, cardiovascular, cancerous, and neurological morbidities. Due to the negative effects of the gene, it is likely frequent due to genetic drift or natural selection. Using secondary data gathered by systematic review, we test proposals stating that under conditions of ample folate, individuals who are heterozygous (CT) and homozygous (TT) for the MTHFR C677T polymorphism would suffer from fewer or no deleterious pregnancy or birth outcomes. Using descriptive and bivariate statistics, we determined if significant differences exist between pregnancy or birth outcomes based on genotype. We then modeled the effects of genotype, folate, cobalamin, and homocysteine (and their interactions) on the frequency of the pregnancy outcomes. Even with ample and high serum folate, CT and TT women sampled had worse pregnancy outcomes. Folate (sometimes interacting with insolation) mediates pregnancy outcomes in a genotype-dependent fashion. For this reason, we caution against the use of a "one size fits all" approach to clinical treatment for CT and TT individuals. We conclude that natural selection is the primary force of evolution acting on this mutation despite its numerous negative effects. We reject the hypothesis that in conditions of ample folate supply, CT or TT pregnant people might have a fitness advantage. Genotype was a strong predictor of birth outcomes, indicating that for this polymorphism, there is a strong folate-genotypic and genotype-insolation interaction.

Abstract Background Gout is a chronic metabolic disorder frequently complicated by thrombotic events. Genetic variants in hemostasis-related genes may contribute to individual susceptibility to thrombosis in gout patients. Objective To assess the association between polymorphisms in hemostasis genes and thrombotic risk in patients with gout. Methods A case–control study was conducted involving 83 patients with gout and 41 healthy controls. Genomic DNA was extracted from peripheral blood leukocytes. Polymorphisms in MTHFR (C677T), F2 (G20210A), F5 (G1691A), and PAI-1 (675 4G/5G) genes were analyzed using multiplex TaqMan real-time PCR. Results Significant differences were observed for MTHFR C677T and PAI-1 4G/5G polymorphisms. The MTHFR CC and PAI-1 4G/4G genotypes were more frequent in the gout group, potentially indicating increased thrombotic risk. In contrast, the MTHFR CT and PAI-1 5G/5G genotypes were more common in controls. No statistically significant associations were found for F2 and F5 variants. Conclusion Our findings suggest that MTHFR C677T and PAI-1 4G/5G polymorphisms may contribute to thrombotic predisposition in patients with gout. These results underscore the need for further research to clarify the clinical relevance of these variants in thrombosis risk stratification.

Background Genetic susceptibility to diabetic nephropathy (DN) has been well-recognized. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in homocysteine metabolism. Variations in the MTHFR gene, particularly the C677T variant, have been implicated in the development of macrovascular and microvascular complications. Objectives This study investigates the relationship between the MTHFR C677T genotype and the occurrence of diabetic nephropathy in type 2 diabetes mellitus (T2DM) patients. Methods A total of 50 T2DM patients were analyzed for urinary albumin/creatinine ratio, which was used to classify them into two groups: 26 patients without nephropathy and 24 with nephropathy. Additionally, the study included 30 first-degree relatives (FDRs) of diabetic patients and 20 healthy controls. Diagnostic tests performed included fasting blood glucose, HbA1c, and serum creatinine levels. Plasma total homocysteine levels were measured using a chemiluminescent assay, and the MTHFR C677T polymorphism was analyzed using PCR-restriction fragment length polymorphism (RFLP). Results Among T2DM patients with nephropathy, the distribution of MTHFR genotypes (CC homozygous, CT heterozygous, and TT homozygous) was 20.8%, 54.2%, and 25%, respectively. The T allele frequency was significantly higher in patients with nephropathy (69.2%) compared to those without nephropathy (23.1%), normal controls (26.7%), and FDRs (30%). There was no significant difference in MTHFR genotype or allele frequency between T2DM patients without nephropathy, FDRs, and healthy controls (p &lt; 0.05). The T allele showed a strong association with the development of diabetic nephropathy. Additionally, plasma homocysteine levels were significantly elevated in individuals with TT or CT genotypes compared to those with the CC genotype, with higher levels correlating with the progression of nephropathy. Conclusion The findings suggest that the C677T mutation in the MTHFR gene predisposes T2DM patients to diabetic nephropathy. The presence of the T allele may elevate plasma homocysteine levels, contributing to the progression of nephropathy toward end-stage renal failure. These results highlight the potential role of the MTHFR C677T variant as a genetic marker for susceptibility to diabetic nephropathy in T2DM patients. BJMS, Vol. 24 No. 03 July’25 Page : 799-806

Background: Myocardial ischemia remains a major cause of morbidity and mortality worldwide. Although traditional risk factors are well-established, genetic predisposition—particularly involving MTHFR polymorphisms—has garnered increasing attention. This study investigates the association between MTHFR C677T and A1298C polymorphisms and first-episode myocardial ischemia in a Romanian population. Methods: This study included 69 adult patients with first-episode myocardial ischemia and 55 healthy controls, matched by age and sex. Participants were recruited from southeastern Romania between 2023 and 2025. Clinical data—such as blood pressure, body mass index, smoking, and alcohol consumption—were recorded. Genotyping for MTHFR C677T and A1298C polymorphisms was performed using a real-time PCR-based assay (Bosphore® MTHFR 677-1298 Detection Kit v2), following the manufacturer’s protocol. Results: A significantly higher frequency of homozygous mutant genotypes was observed in patients with myocardial ischemia. The TT genotype of MTHFR C677T was present in 71% of patients, compared to only 7.3% of controls. Similarly, the CC genotype of A1298C was detected in 59.4% of patients, versus 7.3% in controls. These genotypic patterns suggest a strong genetic predisposition among affected individuals. The association between MTHFR polymorphisms and myocardial ischemia was particularly evident in participants over 50 years of age, indicating a possible interaction between genetic vulnerability and age-related cardiovascular risk. Conclusions: Our findings indicate a strong association between MTHFR C677T and A1298C homozygous mutant genotypes and the risk of first-episode myocardial ischemia, particularly in older adults. These results underscore the potential role of genetic screening in early cardiovascular risk stratification.

Stroke is the second leading cause of death globally and a major contributor to disability. Developing countries report the highest rates of stroke, with ischemic stroke being the most prevalent type. This study aimed to explore the potential association between specific single nucleotide polymorphisms (SNPs) and thrombotic strokes in Egyptian patients, as well as the role of DNA methylation in the promoter regions of genes associated with these SNPs. The study involved 100 adult patients who were consecutively admitted to the International Medical Center. These patients, diagnosed with acute ischemic stroke, were compared to age-matched control subjects (± 3years). Molecular analysis was conducted on six thrombosis-related SNPs: FV (R506Q, H1299R, Y1702C), FII (G20210A), and MTHFR (C677T, A1298C) using blood samples from both stroke patients and healthy controls. DNA methylation in the promoter regions of the FV, FII, and MTHFR genes was assessed through a sodium bisulfite conversion protocol and genomic DNA digestion with the methylation-dependent restriction enzyme MspJI, using specific primers for the promoter regions of FV, FII, and MTHFR in all derived samples. The biochemical analysis of the derived samples revealed elevated levels of homocysteine, ESR, and LDL in stroke patients, alongside reduced levels of both vitamin B12 and serum folate. The SNP analysis of samples from healthy controls and stroke patients, conducted using the TaqMan™ SNP genotyping assay, identified the homozygous SNPs in the FV, FII, and MTHFR genes. The results clearly show that the MTHFR C677T heterozygous mutation is present in nearly all stroke patient samples, with a very low likelihood of this mutation co-occurring with SNP mutations in the other indicated genes. Analysis of methylation activities in the promoter regions of the indicated genes showed hypermethylation in the MTHFR promoter region, while methylation levels in the FV and FII promoter regions were normal. The analysis showed increased methylation of cytosine nucleotide in the MTHFR promoter region, potentially inhibiting MTHFR expression and contributing to the development of thrombotic strokes in patients. Overall, the data support an association between the MTHFR C677T mutation, hypermethylation in its promoter region, and stroke development in the study participants.

Colorectal cancer pathogenesis is a multifactorial process, with genetic factors playing a significant role in cancer development. A review of published meta-analyses on MTHFR gene polymorphisms and colorectal cancer susceptibility showed inconsistent findings and failed to assess the reliability of statistically significant results. Case-control studies were manually searched in databases to investigate the association between MTHFR gene polymorphisms and colorectal cancer. The study assessed the strength of association for the five gene models by calculating odds ratios (ORs) and 95% confidence intervals (CIs). The study results were also analyzed for the source of heterogeneity, sensitivity, publication bias, and false-positive report probability (FPRP) test. Additionally, extensive subgroup analyses were conducted to investigate the impact of confounding factors on the associations. The study suggests that MTHFR C677T gene polymorphism reduces the risk of colorectal cancer in Asian and mixed-race populations, while increasing the risk of Colorectal cancer in the Indian ethnic group. MTHFR A1298C may play a protective role in the development of colorectal cancer. These findings provide valuable insights for the early diagnosis and prevention of Colorectal cancer. However, further studies are required to confirm the association, which may offer additional information for the early diagnosis and prevention of Colorectal cancer.