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Objective: Thrombophilia screening has been performed in patients with conditions such as previous fetal death, (fetal growth restriction) FGR, preeclampsia, (hemolysis. elevated liver enzyme, low platelet count) HELLP Syndrome, previous abruptio placentae, previous thrombosis in pregnancy, and abnormal placental histology. The actual role of hereditary thrombophilia in recurrent pregnancy loss (RPL) is still debated. This study was intended to determine the incidence of specific gene defects for hereditary thrombophilia and to ascertain their impact on RPL in central Anatolia in Turkey. Methods: This retrospective cohort study was performed between January 2012 and December 2022. All pregnant women with a complete hereditary screening profile were included. The investigated gene polymorphisms were methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, Factor V Leiden G1691A, and Factor II prothrombin G20210A. Cases of pregnant women at least two or more consecutive pregnancy losses before 22 weeks of gestation were defined as RPL. The rates of genetic screening and their association with RPL were analyzed. Results: RPL was identified in 224 (27.58%) of the 812 pregnant women with complete genetic screening. Although there was no difference in terms of age, body mass index, numbers of ectopic pregnancies, molar pregnancies, or dilatation & curettage (p > 0.05), gravity (2.0 [2.0–3.0] vs. 4.0 [3.0–5.0]), parity (1.0 [1.0–2.0] vs. 1.0 [0–1.0]), live birth (1.0 [1.0–2.0] vs. 1.0 [0–1.0]), anembryonic pregnancy (0 [0–0] vs. 0 [0–0]), miscarriage (0 [0–1.0] vs. 3.0 [2.0–3.0]), and stillbirth (0 [0–0] vs. 0 [0–0]) numbers differed significantly between the groups (p < 0.05). While no significant differences were determined in MTHFR A1298C, Factor V Leiden, factor II prothrombin G20210A, or homocysteine levels (p > 0.05), the homozygous MTHFR C677T positivity rates differed significantly (6.3% in the non-RPL group vs. 11.6% in the RPL group, p = 0.027). Conclusion: The homozygous MTHFR C677T polymorphisms was found to be more frequent in women with RPL. Further studies with larger cohorts are needed to confirm our results. [ABSTRACT FROM AUTHOR]

AbstractOsteoporosis is a common age-related skeletal disease, characterized by changes in the microarchitectural structure of bone tissue and decreased bone mass, especially affecting postmenopausal women. Genetic and environmental factors affecting bone metabolism play a role in the development of osteoporosis. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in the conversion of homocysteine to methionine. Genetic variations in the MTHFR gene lead to impaired function or inactivation of this enzyme. A decrease in MTHFR enzyme activity and an increase in homocysteine levels affect bone metabolism. In this study, we aimed to investigate the relationship between C677T and A1298C polymorphisms and osteoporosis in Turkish postmenopausal women. DNA samples were extracted from 200 volunteers. The PCR-RFLP technique was used to identify the MTHFR gene polymorphisms C677T and A1298C. The statistical significance of the analysis’s results was assessed. C677T genotype and allele frequency distributions were not statistically different between postmenopausal osteoporosis and healthy control groups (p = 0.249, p = 0.754), while A1298C genotype and allele frequency distributions were found to be statistically significant (p = 0.002, p = 0.013). The results of our study showed that the A1298C polymorphism may be a genetic factor associated with osteoporosis in this specific population. However, the C677T polymorphism did not show a significant connection. To gain a more comprehensive understanding of the genetic basis of osteoporosis, future research with larger sample sizes and the consideration of additional genetic and environmental factors is essential. Additionally, it is crucial to account for ethnic disparities, gene-gene interactions, and gene-environment interplays. These insights can inform the development of personalized preventive and therapeutic strategies for individuals at risk of osteoporosis in diverse populations. [ABSTRACT FROM AUTHOR]

Mutation of methylenetetrahydrofolate reductase (MTHFR) C677T leads to the decrease of folate utilization and the impairment of spermatogenesis. This study attempts to investigate the association between MTHFR C677T polymorphisms and nonobstructive oligozoospermia, asthenozoospermia or oligoasthenozoospermia in the Chinese population. The study cohort comprised 189 patients diagnosed with oligozoospermia, asthenozoospermia or oligoasthenozoospermia, and 626 controls based on clinical examinations. The MTHFR c.677 genotype of all subjects was determined by fluorescence staining in situ hybridization and the significance of different genotype frequencies was further analyzed by Chi-square test. The results showed that the frequency of MTHFR 677 CT genotype in the oligozoospermia, asthenozoospermia and oligoasthenozoospermia group was 33.3%, 38.3% and 44.0% respectively, whereas it was 47.3% in the control group. The P value of Chi-square test was 0.070, 0.103 and 0.654, respectively. The frequency of MTHFR 677 TT genotype in the oligozoospermia, asthenozoospermia and oligoasthenozoospermia group was 31.1%, 11.7% and 18.0% respectively, while that in the control group was 19.5%. The P value of Chi-square test was 0.061, 0.070 and 0.066, respectively. Collectively, there is a weak association between MTHFR C677T polymorphisms and oligozoospermia, asthenozoospermia or oligoasthenozoospermia within the current Chinese population cohort. [ABSTRACT FROM AUTHOR]

Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating one-carbon metabolism. Polymorphisms within the MTHFR gene have been found to increase the risk of breast cancer in different populations. In this study, we evaluated the association of polymorphisms of the MTHFR gene (rs1801133 and rs1801131) with the risk of breast cancer in the Bangladeshi population. This case‒control study included 202 breast cancer patients and 104 healthy controls. After the organic extraction of DNA, genotyping was performed via the PCR-RFLP method. Sanger sequencing was performed to validate the RFLP data. Statistical analyses were performed to evaluate the associations of the polymorphisms. Different computational tools were used to predict the structural and functional consequences of the SNPs. Our study revealed that the MTHFR gene polymorphism rs1801131 is associated with an increased risk of developing breast cancer (p < 0.001, OR = 3.85, 95% CI = 2.06–7.25 for the AC genotype and p < 0.001, OR = 7.82, 95% CI = 2.69–22.05 for the CC genotype). An association was also observed in the dominant model (AC + CC) (p < 0.001, OR = 4.19, 95% CI = 2.28–7.78). For rs1801131, premenopausal status was significantly associated with breast cancer risk (p < 0.001). For rs1801133, no significant association was found with breast cancer risk (p > 0.05, OR = 1.57, 95% CI = 0.90–2.74 for the CT genotype; p > 0.05, OR = 1.35, 95% CI = 0.36–4.92 for the TT genotype). Computational analyses predicted rs1801131 to be tolerated and rs1801133 to be deleterious. Structural analyses demonstrated no significant changes in protein structure but revealed alterations in neighboring interactions according to both bond distances and angles. In conclusion, rs1801131 but not rs1801133 is significantly associated with breast cancer risk in the Bangladeshi population. Moreover, in silico analyses demonstrated changes in the interaction pattern of polymorphic residues with adjacent amino acids. [ABSTRACT FROM AUTHOR]

Vitamin B12 deficiency is a common condition that causes a variety of disorders ranging from the development of megaloblastic anemia to the building up of neurological damage. Historically one of the leading causes of B12 deficiency appears to be secondary to malabsorption in part caused by the development of atrophic gastritis in pernicious anemia. More recently B12 deficiency could also depend on dietary restrictions. Cobalamin deficiency also appears to be closely related to folate metabolism, causing a reduction in methionine synthase activity. This results in the accumulation of 5-methyltetrahydrofolate (5-MTHF) and defective DNA synthesis. It has been hypothesized that reduced activity of the enzyme methylene-tetrahydrofolate reductase (MTHFR) could reduce the production of 5-MTHF, thereby shifting folate metabolism to thymidylate synthesis and promoting proper DNA synthesis. Our aim was to investigate the role of the C677T and A1298C MTHFR gene polymorphisms, which are associated with reduced enzyme activity, in predisposing to the development of anemia, neurological symptoms, and atrophic gastritis in a population of 105 consecutive Italian patients with cobalamin deficiency. We found statistically significant correlations between the degree of anemia and thrombocytopenia and the C677T MTHFR polymorphism, while hemoglobin levels alone significantly correlated with A1298C polymorphism, contradicting the potential protective role of these polymorphisms. Furthermore, in patients with atrophic gastritis, we found an association between the absence of parietal cell antibodies and the presence of the C677T polymorphism in homozygosity. Our results suggest a role for MTHFR enzyme activity in the severity of hematologic manifestations of vitamin B12 deficiency and as an independent mechanism of predisposition to the development of atrophic gastritis. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) poses a substantial risk to prenatal and maternal health. Folic acid (FA) and methylenetetrahydrofolate reductase (MTHFR) play roles in DNA methylation and genomic integrity maintenance, with MTHFR polymorphisms potentially impacting PE occurrence. Human microRNA 149 (miR-149) remains underexplored in PE despite its involvement in folate metabolism. This study seeks to evaluate serum miR-149 levels with the MTHFR C677T polymorphism for diagnosing PE. Methods: Seventy females aged 28–40 gestational weeks were divided into control and Preeclampsia groups. Serum miR-149 and MTHFR gene levels were evaluated using real-time PCR. Results: Preeclamptic patients showed significantly lower serum miR-149 levels than healthy controls (P ≤ 0.01). PE cases showed a higher frequency of the TT genotype and T allele of the C677T polymorphism (OR = 0.181, 2.882, respectively), implicating them as genetic risk factors. The CT genotype also increased PE risk (OR = 0.26), while no significant difference was observed in the CC genotype. Conclusion: Merging miR-149 and MTHFR polymorphism assessment improves discrimination between healthy and PE groups, offering valuable insights into PE pathogenesis and potential diagnostic strategies. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary embolism (PE), the most serious presentation of venous thromboembolism (VTE), is associated with a high rate of mortality and expense. Clinical studies on pregnant women with PE are scarce. The aim of this study was to analyze the clinical impact of fibrinolytic enzyme activation inhibitor-1 (PAI-1) 4G/5G genetic polymorphisms, methylenetetrahydrofolate reductase (MTHFR) rs1801131 (A1298C) and rs1801133 (C677T) genetic polymorphisms, and establish a predictive model for pregnant women. Material and Methods: Between September 2022 and August 2023, 53 pregnant women with PE were enrolled. Using the propensity score matching method, 106 consecutive pregnant women without VTE were 1:2 matched. The relevant patient data were collected, and the susceptibility genes for PE were detected to determine genetic polymorphisms, and PE susceptibility in pregnant women, as well as to develop predictive models. Results: Our study showed that 4G/4G homozygous mutations increased the risk of pregnant PE fourfold (OR = 4.46, 95% CI = 1.59– 12.50, P = 0.004), whereas the 4G allele mutation increased the risk twofold (OR = 2.33, 95% CI = 1.35– 4.04, P = 0.002). A nomogram was established to predict the risk of pregnant women with PE by four predictive features including PAI-1 genetic polymorphisms, international normalized ratio (INR), antithrombin-III (AT-III) activity, and platelet count (PLT). The area under the curve (AUC) of the nomogram was 0.821 (0.744– 0.898). The AUC of the internal validation group was 0.822 (0.674– 0.971). Decision curve analysis revealed that the nomogram has a higher net benefit in the following threshold: probability interval of ≥ 15%. Conclusion: The PAI-1 4G/4G genotype is an independent risk factor for pregnant women with PE; furthermore, the presence of the 4G allele can increase the risk of PE. The study established a nomogram to predict the risk of PE in pregnant women. [ABSTRACT FROM AUTHOR]

Introduction: Ischemic stroke (IS) is a global health concern, often tied to dyslipidemia and vascular endothelial dysfunction. MicroRNA-34a (miR-34a) was reported to be up-regulated in the blood samples of patients with IS, but the specific role of miR-34a and methylenetetrahydrofolate reductase (MTHFR) in IS remains to be elucidated. Methods: We studied 143 subjects: 71 IS patients, and 72 healthy controls. Human umbilical vein endothelial cells (HUVECs) were cultured and transfected with a miR-34a mimic, inhibitor, or negative control. The miR-34a expression in serum and HUVECs was quantified via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Viability and apoptosis of HUVECs were assessed using CCK-8 assay and flow cytometry. The expression levels of bcl-2, bax, cyt-c, cleaved caspase 3, MTHFR, and homocysteine were measured by Western blot or enzyme-linked immunosorbent assay (ELISA). The relationship between miR-34a and MTHFR was verified by luciferase reporter assay. The levels of MTHFR and homocysteine in serum were examined by ELISA. Results: MiR-34a expression was increased in IS patients and inhibited viability of HUVECs while promoting their apoptosis. Overexpression of miR-34a up-regulated pro-apoptotic proteins (bax, cyt-c and cleaved caspase 3) and down-regulated anti-apoptotic protein bcl-2 in HUVECs. MTHFR was identified as the downstream target of miR-34a and its expression was reduced by miR-34a overexpression, while homocysteine levels increased. Consistently, MTHFR levels were lower and homocysteine levels were higher in IS patients compared with controls. Discussion: Our results suggest that up-regulated miR-34a plays a role in the pathogenesis of IS, potentially through inhibiting MTHFR expression and increasing homocysteine in endothelial cells. Therefore, miR-34a might be a therapeutic target for IS [ABSTRACT FROM AUTHOR]

Simple Summary: Preeclampsia is a severe complication of pregnancy with no clear etiology but confirmed to have complex pathogenetic mechanisms involved. Previous research evidence reported associations between folate metabolism genes' polymorphisms and preeclampsia. This study aimed to evaluate the prevalence of methionine synthase (MTR), methionine synthase reductase (MTRR), and methylenetetrahydrofolate reductase (MTHFR) genes' polymorphisms among ethnic Kazakh women with preeclampsia. The results of this study provide a basic understanding of folate metabolism genes' polymorphisms in preeclampsia among the Central Asian population. Introduction: Preeclampsia is a severe multifactorial complication of pregnancy. Studies found associations between folate metabolism genes' polymorphisms and preeclampsia. However, investigations in this field are limited among Asian populations. Thus, the study's aim was to evaluate the prevalence of methionine synthase (MTR), methionine synthase reductase (MTRR), and methylenetetrahydrofolate reductase (MTHFR) genes' polymorphisms among ethnic Kazakh women with preeclampsia. Methods: This was a retrospective study involving 4246 patients' data for the period of 2018–2022. Identification of MTR, MTRR, and MTHFR genes' polymorphism was performed via PR-PCR. Peripheral blood samples were obtained for the analyses. In total, 4246 patients' data of Kazakh ethnicity with preeclampsia at >20 weeks gestational age who had undergone an investigation to identify polymorphisms of the folate metabolism pathway genes for the period of 5 years were included in this study. Results: The most common and prevalent mutation was the MTRR A66G polymorphism: 24.5% of all tested patients with preeclampsia had the MTRR A66G polymorphism. It was highest among the 35–39 age group participants. The second most prevalent was the MTHFR C677T polymorphism: 9% of women with preeclampsia had the MTHFR C677T mutation. It was highest among women aged 30–34. There was a rare association of the MTR A2756G mutation with preeclampsia among the study participants. Conclusions: The identified levels of MTRR A66G and MTHFR C677T polymorphisms among the study participants suggest the importance of evaluating MTRR and MTHFR polymorphisms in women with preeclampsia. The role of the MTR A2756G polymorphism in the development of preeclampsia needs to be further investigated. [ABSTRACT FROM AUTHOR]

The methylenetetrahydrofolate reductase (MTHFR) gene 677C➔T polymorphism is capable of altering folate metabolism and can modify certain neoplasia risk. Reports have suggested that folate can have an influence on bone development and so it is of interest to know if the MTHFR 677C➔T polymorphism is associated with the malignant transformation process of this tissue. The polymorphism was determined in 55 patients with osteosarcoma and in 180 healthy individuals. Compared with C/T+C/C genotypes, a 3.7-fold reduction in osteosarcoma probability is possible with the T/T genotype (OR 0.27, CI 95% 0.07–0.82). Undoubtedly, further studies, utilizing large samples and carried out on different populations, are necessary to confirm these results. [ABSTRACT FROM AUTHOR]

Background: Cleft lip with or without cleft palate (CL/P) is the most common congenital anomaly found in Indonesia. CL/P is caused by hereditary (genetic) and environmental factors. Environmental factors can result in methylation in the promoter of the methylenetetrahydrofolate reductase (MTHFR) gene, affecting its expression. Methylation takes place at the CpG site found at chromosome 1, coordinates 11,805,406-11,806,509. Pyrosequencing technology can detect the percentage methylation of a gene quickly, simply, and accurately. Purpose: The aim of the study is to optimize detection of methylation of the MTHFR gene using the pyrosequencing method. Methods: Methods used in this study were DNA extraction from blood, DNA bisulfite conversion, polymerase chain reaction (PCR), and methylation detection using CpG pyrosequencing assay. Samples were taken from 20 CL/P patients (C) and 44 normal patients (N). Results: The pyrosequencing method was successful in detecting methylation at three MTHFR gene sites at coordinates 11,805,507-11,805,529. The methylation level at the third site was higher in group C than in group N, while at the first and second positions, group C had a lower methylation level than group N. In general, the percentage of methylation for both groups was low or hypomethylated (less than 5%). Conclusion: The pyrosequencing method can be used to determine methylation levels in the MTHFR gene with the results presented as percentages (quantitative data). Hypomethylation occurs in groups C and N at the coordinates 11,805,507-11,805,529 of the MTHFR gene promoter. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease is a neurodegenerative disorder with polygenic etiology. Genetic risk variants for Alzheimer’s disease differ among populations. Thus, discovering them in each population is clinically important. A total of 118 patients and 97 controls for VDR rs11568820 and 88 patients and 100 healthy controls for MTHFR C677T polymorphism were genotyped to evaluate the association of these polymorphisms with late-onset Alzheimer’s disease in the Iranian population, along with their impacts on the response to Rivastigmine treatment. The VDR C allele was significantly associated with Alzheimer’s disease and provided protection against it (P = 0.003, RR = 1.14, 95% CI 1.04–1.24), while the T allele increased susceptibility (P = 0.003, RR = 1.93, 95% CI 1.23–3.02). These results were also considerable upon excluding the effect of APOE ε4 allele. The Prevalence-corrected Positive Predictive Value was 1.71% for the VDR CC genotype and 4% for the VDR CT genotype, indicating lower and almost twofold higher chances of developing Alzheimer’s disease, respectively. No significant correlation was observed between MTHFR C677T and Alzheimer’s disease. Based on our pharmacogenetic study, MTHFR T allele carriers lacking APOE ε4 allele showed a better response to Rivastigmine treatment after a 2-year follow-up. Moreover, patients with VDR CC genotype displayed milder Alzheimer’s disease, particularly when coincided with the APOE ε4 allele. The VDR rs11568820 polymorphism affects both Alzheimer’s disease risk and the response to Rivastigmine in Iranian patients. Also, MTHFR C677T polymorphism may play a role in the response to Rivastigmine, through a pathway that needs to be elucidated in future studies. [ABSTRACT FROM AUTHOR]

Abstract Objective Thrombophilia screening has been performed in patients with conditions such as previous fetal death, (fetal growth restriction) FGR, preeclampsia, (hemolysis. elevated liver enzyme, low platelet count) HELLP Syndrome, previous abruptio placentae, previous thrombosis in pregnancy, and abnormal placental histology. The actual role of hereditary thrombophilia in recurrent pregnancy loss (RPL) is still debated. This study was intended to determine the incidence of specific gene defects for hereditary thrombophilia and to ascertain their impact on RPL in central Anatolia in Turkey. Methods This retrospective cohort study was performed between January 2012 and December 2022. All pregnant women with a complete hereditary screening profile were included. The investigated gene polymorphisms were methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, Factor V Leiden G1691A, and Factor II prothrombin G20210A. Cases of pregnant women at least two or more consecutive pregnancy losses before 22 weeks of gestation were defined as RPL. The rates of genetic screening and their association with RPL were analyzed. Results RPL was identified in 224 (27.58%) of the 812 pregnant women with complete genetic screening. Although there was no difference in terms of age, body mass index, numbers of ectopic pregnancies, molar pregnancies, or dilatation & curettage (p > 0.05), gravity (2.0 [2.0–3.0] vs. 4.0 [3.0–5.0]), parity (1.0 [1.0–2.0] vs. 1.0 [0–1.0]), live birth (1.0 [1.0–2.0] vs. 1.0 [0–1.0]), anembryonic pregnancy (0 [0–0] vs. 0 [0–0]), miscarriage (0 [0–1.0] vs. 3.0 [2.0–3.0]), and stillbirth (0 [0–0] vs. 0 [0–0]) numbers differed significantly between the groups (p 0.05), the homozygous MTHFR C677T positivity rates differed significantly (6.3% in the non-RPL group vs. 11.6% in the RPL group, p = 0.027) . Conclusion The homozygous MTHFR C677T polymorphisms was found to be more frequent in women with RPL. Further studies with larger cohorts are needed to confirm our results.

Abstract Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating one-carbon metabolism. Polymorphisms within the MTHFR gene have been found to increase the risk of breast cancer in different populations. In this study, we evaluated the association of polymorphisms of the MTHFR gene (rs1801133 and rs1801131) with the risk of breast cancer in the Bangladeshi population. This case‒control study included 202 breast cancer patients and 104 healthy controls. After the organic extraction of DNA, genotyping was performed via the PCR-RFLP method. Sanger sequencing was performed to validate the RFLP data. Statistical analyses were performed to evaluate the associations of the polymorphisms. Different computational tools were used to predict the structural and functional consequences of the SNPs. Our study revealed that the MTHFR gene polymorphism rs1801131 is associated with an increased risk of developing breast cancer (p 0.05, OR = 1.57, 95% CI = 0.90–2.74 for the CT genotype; p > 0.05, OR = 1.35, 95% CI = 0.36–4.92 for the TT genotype). Computational analyses predicted rs1801131 to be tolerated and rs1801133 to be deleterious. Structural analyses demonstrated no significant changes in protein structure but revealed alterations in neighboring interactions according to both bond distances and angles. In conclusion, rs1801131 but not rs1801133 is significantly associated with breast cancer risk in the Bangladeshi population. Moreover, in silico analyses demonstrated changes in the interaction pattern of polymorphic residues with adjacent amino acids.

The methylenetetrahydrofolate reductase (MTHFR) gene 677C➔T polymorphism is capable of altering folate metabolism and can modify certain neoplasia risk. Reports have suggested that folate can have an influence on bone development and so it is of interest to know if the MTHFR 677C➔T polymorphism is associated with the malignant transformation process of this tissue. The polymorphism was determined in 55 patients with osteosarcoma and in 180 healthy individuals. Compared with C/T+C/C genotypes, a 3.7-fold reduction in osteosarcoma probability is possible with the T/T genotype (OR 0.27, CI 95% 0.07–0.82). Undoubtedly, further studies, utilizing large samples and carried out on different populations, are necessary to confirm these results.

Folate metabolism is required for important biochemical processes that regulate cell functioning, but its role in female reproductive physiology in cattle during peri- and post-conceptional periods has not been thoroughly explored. Previous studies have shown the presence of folate in bovine oviductal fluid, as well as finely regulated gene expression of folate receptors and transporters in bovine oviduct epithelial cells (BOECs). Additionally, extracellular folic acid (FA) affects the transcriptional levels of genes important for the functioning of BOECs. However, it remains unknown whether the anatomical and cyclic features inherent to the oviduct affect regulation of folate metabolism. The present study aimed to characterize the gene expression pattern of folate cycle enzymes in BOECs from different anatomical regions during the estrous cycle and to determine the transcriptional response of these genes to increasing concentrations of exogenous FA. A first PCR screening showed the presence of transcripts encoding dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase (MTR) in bovine reproductive tissues (ovary, oviduct and uterus), with expression levels in oviductal tissues comparable to, or even higher than, those detected in ovarian and uterine tissues. Moreover, expression analysis through RT-qPCR in BOECs from the ampulla and isthmus during different stages of the estrous cycle demonstrated that folate metabolism-related enzymes exhibited cycle-dependent variations. In both anatomical regions, DHFR was upregulated during the preovulatory stage, while MTHFR and MTR exhibited increased expression levels during the postovulatory stage. Under in vitro culture conditions, ampullary and isthmic cells were cultured in the presence of 10, 50, and 100 μM FA for 24 h. Under these conditions, isthmus epithelial cells exhibited a unique transcriptional response to exogenous FA, showing a pronounced increase in MTR expression levels. Our results suggest that the expression of folate metabolism-related genes in BOECs is differentially regulated during the estrous cycle and may respond to exogenous levels of folate. This offers a new perspective on the transcriptional regulation of genes associated with the folate cycle in oviductal cells and provides groundwork for future studies on their functional and epigenetic implications within the oviductal microenvironment. • Genes related to folate metabolism enzymes are expressed in bovine oviduct ephitelial cells (BOECs). • DHFR , MTHFR , and MTR expression levels exhibit cycle-dependent variations in BOECs from ampulla and isthmus regions. • MTR is upregulated in isthmus cells cultured with increasing levels of folic acid. • Folate metabolism could have important functional and epigenetic implications in the bovine oviduct. [ABSTRACT FROM AUTHOR]

Abstract Background Methylenetetrahydrofolate reductase (MTHFR) is essential for the metabolism of folic acid and homocysteine. The MTHFR C677T polymorphism is associated with several disorders. Our study aims to explore the geographical distributions of the MTHFR C677T polymorphism of women in China and how migration affected the polymorphism in Suzhou. Methods A total of 7188 women of reproductive age were recruited in Suzhou of the study. Subjects were classified according to their native places after data extraction. MTHFR C677T gene polymorphisms were detected by quantitative PCR with genomic DNA isolated from blood samples. Results The frequencies of the 677T allele and 677TT genotype were higher in northern China than that in southern China and decreased in geographical gradients from north to south. The frequencies were considerably higher in the migrant population than that in the indigenous population of Suzhou. The migrant population have gradually changed the prevalence in Suzhou. Conclusions Our study suggested that the prevalence of MTHFR C677T polymorphisms among women varied across different geographical regions in Chinese Han populations. The 677T allele frequencies of the northern populations were significantly higher than those of the southern populations. The migrant population gradually changed the prevalence of the MTHFR C677T polymorphism in Suzhou.

Major depressive disorder (MDD) is considerably heterogeneous in terms of comorbidities, which may hamper the disentanglement of its biological mechanism. In a previous study, we classified the lifetime trajectories of MDD-related multimorbidities into seven distinct clusters, each characterized by unique genetic and environmental risk-factor profiles. The current objective was to investigate genome-wide gene-by-environment (G × E) interactions with childhood trauma burden, within the context of these clusters. We analyzed 77,519 participants and 6,266,189 single-nucleotide polymorphisms (SNPs) of the UK Biobank database. Childhood trauma burden was assessed using the Childhood Trauma Screener (CTS). For each cluster, Plink 2.0 was used to calculate SNP × CTS interaction effects on the participants' cluster membership probabilities. We especially focused on the effects of 31 candidate genes and associated SNPs selected from previous G × E studies for childhood maltreatment's association with depression. At SNP-level, only the high-multimorbidity Cluster 6 revealed a genome-wide significant SNP rs145772219. At gene-level, MPST and PRH2 were genome-wide significant for the low-multimorbidity Clusters 1 and 3, respectively. Regarding candidate SNPs for G × E interactions, individual SNP results could be replicated for specific clusters. The candidate genes CREB1, DBH , and MTHFR (Cluster 5) as well as TPH1 (Cluster 6) survived multiple testing correction. CTS is a short retrospective self-reported measurement. Clusters could be influenced by genetics of individual disorders. The first G × E GWAS for MDD-related multimorbidity trajectories successfully replicated findings from previous G × E studies related to depression, and revealed risk clusters for the contribution of childhood trauma. • First G × E GWAS with childhood trauma for MDD-related multimorbidity trajectories. • Most G × E findings for high MDD-multimorbidity Clusters 5–6. • Significant correlation between cluster probability and CTS (high vs low risk clusters). • stronger genetic findings in the clusters with higher childhood trauma burden. • Differential effects of candidate genes in different comorbidity clusters. [ABSTRACT FROM AUTHOR]

This article discusses a case where the Taqman system, commonly used for genotyping, failed to accurately identify a specific genetic mutation. The study found that a rare mutation at the MTHFR 679 locus resulted in the failure of genotyping for a different mutation. The authors highlight the importance of adaptability and alternative approaches in genetic testing. They also explore the relationship between this mutation and enzyme activity and susceptibility to recurrent spontaneous abortion. The article provides valuable information on a specific genetic variant and its clinical significance, making it a useful resource for those researching genetics and its connection to specific health conditions. [Extracted from the article]

Purpose: To assess age at 1st central retinal vein occlusion (CRVO) in carriers ≤ 45 years old of the methylenetetrahydrofolate reductase (MTHFR) C667T genotype compared to heterozygous and wild type, and to identify predictors of age at CRVO. Methods: Retrospective cohort study consisting of 18 MTHFR TT, 23 MTHFR TC and 28 MTHFR CC participants; information regarding age, sex, age at CRVO, history of dyslipidaemia, hypertension, smoking and plasma HC measured by immunoassay were collected. Results: Age at CRVO was lower in MTHFR TT than MTHFR TC and CC (32 ± 6 vs 38 ± 5 vs 37 ± 6 years, respectively, p = 0.005); plasma HC was higher in MTHFR TT than in the other genotypes [14.4 (10.8, 19.6) vs 10.4 ((8.6,12.5) vs 8.5 ((7.5,9.8) μmol/l, p = 0.0002). Smoking (cigarettes/day) independently predicted age at CRVO (p = 0.039) and plasma HC (p = 0.005); smoking status (yes/no) predicted ischemic CRVO (p = 0.01) that was more common in the MTHFR TT group (p = 0.006). Conclusions: Carriers of the MTHFR TT genotype ≤ 45 years old develop their 1st CRVO on average 5 years earlier than the MTHFR CC genotype; smoking contributes to the prematurity and severity of CRVO in MTHFR TT carriers. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) patients present a high prevalence of cardiometabolic risk, associated with worse clinical manifestations and mortality. Folate, an essential micronutrient that participates in vital immune cellular functions, could positively affect the cardiometabolic and disease risk in SLE, through the methylenetetrahydrofolate reductase (MTHFR) enzyme, which participates in the folate metabolism, where single nucleotide variants (SNVs) have been described as a potential genetic risk factor for SLE. The aim of this study was to determine the association of the c.+677 C>T (rs1801133) and c.+1298 A>C (rs1801131) MTHFR genetic variants with cardiometabolic risk and clinical disease variables in SLE patients. A case-control study was conducted on 394 unrelated Mexican-mestizo women: 199 with SLE according to the 1997 SLE-ACR criteria and 196 control subjects (CS). Folic acid and homocysteine levels were evaluated by immunoassays. Genotyping of MTHFR genetic variants was carried out by allelic discrimination. No significant differences were found for folic acid (p =.15) and homocysteine serum levels (p =.59) between groups. According to the CC c.+677 MTHFR genotype, this was associated with low cardiovascular disease (CVD) risk by the Castelli index (OR = 0.42; p =.03) in SLE patients. The TC (OR = 1.3; p =.03) and the TA (OR = 1.6; p <.01) haplotypes from c.+677 C>T plus c.+1298 MTHFR were associated with SLE risk, while the CC MTHFR haplotype (OR = 0.5; p =.01) was found as a non-risk factor for the disease. In conclusion, the TC and the TA MTHFR haplotypes are associated with disease risk; meanwhile, the CC c.+677 MTHFR genotype confers lower cardiometabolic risk in Mexican-mestizo SLE patients. [ABSTRACT FROM AUTHOR]

Objectives: Many single nucleotide polymorphisms affect the incidence of Alzheimer's disease (AD). This investigation aimed to consider the frequency of the C677T single nucleotide polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in Alzheimer's patients. Materials and Methods: This study was conducted in two groups of control (n = 80) and patient (n = 80) with a ratio of 1: 1 male to female. Amplification-refractory mutation system-Polymerase Chain Reaction (ARMS-PCR) method was used to study mutations and ELISA was used to measure homocysteine and the chemiluminescence method was used to measure cholesterol, vitamin B12 and folate. Results: Based on the results of the PCR test of the MTHFR gene, the incidence rate of mutation in the healthy allele was 44.6% and in the mutant allele was 27.9% of the total study population. Conclusion: In this study, it was discovered that an increase in cholesterol levels is related with an increased risk of developing the disease, but more studies are needed to confirm this. It should also be noted that this increase is not related to the MTHFR gene polymorphism at the C677T position. [ABSTRACT FROM AUTHOR]

Aim: Remethylation disorders such as 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency reduce the remethylation of homocysteine to methionine. The resulting hyperhomocysteinemia can lead to serious neurological consequences and multisystem toxicity. The role of MTHFR genotypes has not been investigated in patients with Rett Syndrome (RTT). In this study, we sought to assess the impact of co-occurring MTHFR genotypes on symptom profiles in RTT. Method: Using pharmacogenomic (PGx) testing, the MTHFR genetic polymorphisms rs1801133 (c.665C>T mutation) and rs1801131 (c.1286A>C mutation) were determined in 65 patients (18.7 years ± 12.1 [mean ± standard deviation]) with RTT as part of routine clinical care within the Centre for Interventional Paediatric Psychopharmacology (CIPP) Rett Centre, a National and Specialist Child and Adolescent Mental Health Service (CAMHS) in the UK. The clinical severity of patients was assessed using the RTT-anchored Clinical Global Impression Scale (RTT-CGI). Results: The clinical severity symptom distribution varied between the homozygous and heterozygous MTHFR rs1801133 and rs1801131 genotypes. Those with the homozygous genotype had a narrower spread of severity scores across several domains (language and communication, ambulation, hand-use and eye contact clinical domains). Patients with the homozygous genotype had statistically significantly greater CGI-Severity scores than individuals with a non-homozygous MTHFR genotype (Z = −2.44, p = 0.015). When comparing the ratings of moderately impaired (4), markedly impaired (5), severely impaired (6) and extremely impaired (7), individuals with the homozygous MTHFR genotype were more impaired than those with the non-homozygous MTHFR genotype (Z = −2.06, p = 0.039). There was no statistically significant difference in the number of prescribed anti-epileptic drugs between the genotypes. Conclusions: Our findings show that in those with a pathogenic RTT genetic variant, co-occurring homozygotic MTHFR rs1801133 and rs1801131 polymorphisms may act as associative genetic modifiers of clinical severity in a subset of patients. Profiling of rs1801133 and rs1801131 in RTT may therefore be useful, especially for high-risk patients who may be at the most risk from symptom deterioration. [ABSTRACT FROM AUTHOR]

Aim: The response rate to pioglitazone and the predictive factors for its effects on improving liver biochemistry in patients with steatotic liver disease (SLD) remain elusive, so we aimed to investigate these issues. Methods: A 3‐year prospective cohort study of 126 Taiwanese patients with SLD treated with pioglitazone (15‐30 mg/day) was conducted. Phospholipase domain‐containing protein 3 I148M rs738409, methylenetetrahydrofolate reductase rs1801133, aldehyde dehydrogenase 2 (ALDH2) rs671 and lipoprotein lipase rs10099160 single nucleotide polymorphisms were assessed in the patients. Results: Of 126 patients, 78 (61.9%) were men, and the mean and median ages were 54.3 and 56.5 years, respectively. Pioglitazone responders were defined as those with decreased alanine aminotransferase (ALT) levels at 6 months post‐treatment, and 105 (83.3%) patients were responders. Compared with non‐responders, responders were more frequently women and had higher baseline ALT levels. The proportion of patients with the ALDH2 rs671 GG genotype was lower among responders (38.6% vs. 66.6%, p =.028). Female sex [odds ratio (OR): 4.514, p =.023] and baseline ALT level (OR: 1.015, p =.046; cut‐off level: ≥82 U/L) were associated with pioglitazone response. Among responders, the liver biochemistry and homeostasis model assessment of insulin resistance improved from 6 to 24 months post‐treatment. The total cholesterol levels decreased within 6 months, while increases in high‐density lipoprotein cholesterol levels and decreases in triglyceride levels and fibrosis‐4 scores were noted only at 24 months post‐treatment. The 2‐year cumulative incidences of cardiovascular events, cancers and hepatic events were similar between responders and non‐responders. Conclusions: Regarding liver biochemistry, over 80% of Taiwanese patients with SLD had a pioglitazone response, which was positively associated with female sex and baseline ALT levels. Insulin resistance improved as early as 6 months post‐treatment, while liver fibrosis improvement was not observed until 24 months post‐treatment. The link between the pioglitazone response and the ALDH2 genotype warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Maternal folic acid intake has been associated with decreased risk for neurodevelopmental disorders including autism spectrum disorder (ASD). Genetic differences in folate metabolism could explain some inconsistencies. To our knowledge, newborn folate concentrations remain unexamined. Methods: We measured folate in archived newborn dried blood spots of children from the CHARGE (Childhood Autism Risks from Genetics and the Environment) case–control study who were clinically confirmed at 24–60 months to have ASD (n = 380), developmental delay (n = 128), or typical development (n = 247). We quantified monthly folic acid intake from maternally-reported supplements and cereals consumed during pregnancy and 3 months prior. We assessed associations of newborn folate with maternal folic acid intake and with ASD or developmental delay using regression. We stratified estimates across maternal and child MTHFR genotypes. Results: Among typically developing children, maternal folic acid intake in prepregnancy and each pregnancy month and prepregnancy prenatal vitamin intake were positively associated with newborn folate. Among children with ASD, prenatal vitamin intake in pregnancy months 2–9 was positively associated with newborn folate. Among children with developmental delay, maternal folic acid and prenatal vitamins during the first pregnancy month were positively associated with neonatal folate. Associations differed by MTHFR genotype. Overall, neonatal folate was not associated with ASD or developmental delay, though we observed associations with ASD in children with the MTHFR 677 TT genotype (odds ratio: 1.76, 95% CI = 1.19, 2.62; P for interaction = 0.08). Conclusion: Maternal prenatal folic acid intake was associated with neonatal folate at different times across neurodevelopmental groups. Neonatal folate was not associated with reduced ASD risk. MTHFR genotypes modulated these relationships. [ABSTRACT FROM AUTHOR]

Methylenetetrahydrofolate reductase (MTHFR) is a pivotal flavoprotein connecting the folate and methionine methyl cycles, catalyzing the conversion of methylenetetrahydrofolate to methyltetrahydrofolate. Human MTHFR (hMTHFR) undergoes elaborate allosteric regulation involving protein phosphorylation and S-adenosylmethionine (AdoMet)-dependent inhibition, though other factors such as subunit orientation and FAD status remain understudied due to the lack of a functional structural model. Here, we report crystal structures of Chaetomium thermophilum MTHFR (cMTHFR) in both active (R) and inhibited (T) states. We reveal FAD occlusion by Tyr361 in the T-state, which prevents substrate interaction. Remarkably, the inhibited form of cMTHFR accommodates two AdoMet molecules per subunit. In addition, we conducted a detailed investigation of the phosphorylation sites in hMTHFR, three of which were previously unidentified. Based on the structural framework provided by our cMTHFR model, we propose a possible mechanism to explain the allosteric structural transition of MTHFR, including the impact of phosphorylation on AdoMet-dependent inhibition. Here, the authors present the structure of inactive methylenetetrahydrofolate reductase, revealing linker-mediated allostery coupled with dual SAM binding and revealing distinct domain rearrangements. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) of unknown cause. Alterations in one-carbon metabolism have impact in the pathophysiology by genetic susceptibility to MS and increased the risk of MS. The aim of this study was to investigate the contribution of the gene polymorphism on Methylenetetrahydrofolate Reductase (MTHFR), Methionine Synthase Reductase (MTRR), Methionine Synthase (MTR) enzymes and of the essential factors (homocysteine, Hcy; cysteine, Cys; and vitamin B12, VitB12) in folate metabolism. Eligible MS patients (n = 147) and health controls (n = 127) were participated. The gene polymorphisms were analyzed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and the levels of plasma Hcy, Cys and VitB12 were measured by Enzyme Linked Immunuabsorbent Assay (ELISA). Our results showed that the levels of Hcy and VitB12 were lower and the levels of Cys were higher in MS compared to controls. The observation of high Cys values in all 3 gene polymorphisms suggests that the transsulfiration pathway of Hcy is directed towards Cys formation since the methionine synthesis pathway does not work. We could not find any association with all gene polymorphisms with the risk of MS. The T allele of MTHFR C677T and G allele of MTR A2756G are risk factors for serum Cys level on MS. As for MTR A2756G, serum vitB12 was observed in MS patients with G allele. [ABSTRACT FROM AUTHOR]

Introductıon: This retrospective study evaluated women in whom transvaginal cervical cerclage (TCC) was performed in a previous pregnancy but delivered without cervical intervention in the most recent pregnancy. The primary aim was to underline the importance of etiology based management protocols on favorable pregnancy outcomes in patients with a history of TCC. Methods: We retrospectively evaluated 34 patients with at least one failed TCC for the treatment of cervical insufficiency (CI) but who gave birth without TCC in their most recent pregnancies. Results: All patients were evaluated preconceptionally and examined for maternal risk factors. At least one risk factor was present in all cases. The autoimmune antibody positivity rate was 41.2%. Twelve patients had Hashimoto thyroiditis, two had systemic lupus erythematosus, two had pernicious anemia, and two had anti-phospholipid antibody syndrome. 32 had homozygous or heterozygous methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, while 11 were homozygous or heterozygous for factor 5 Leiden or prothrombin-20210A gene mutations. Conclusion: The elimination and management of risk factors for cervical ripening and dilatation are important for preventing unnecessary cervical interventions. [ABSTRACT FROM AUTHOR]

Background: Various factors, such as genetic causes, anatomic abnormalities of the uterus, infectious diseases, coagulative disorders, and endocrinological and immunological diseases, might influence recurrent pregnancy loss (RLP). This study aimed to evaluate the prevalence and frequency of the FII G20210A, FVL G1691A, and MTHFR C677T polymorphisms in Sudanese women with RPL. Methods and Results: This descriptive cross-sectional study involved 100 women with a history of 3 or more RPLs (the case group) and 94 healthy multiparous women without pregnancy complications (the control group). DNA was extracted from peripheral blood samples. The study of the FII G20210A, FVL G1691A, and MTHFR C677T polymorphisms was performed by PCR and RFLP analysis. For the FII G20210A, the genotype distribution in the case group and control group was as follows: GG=97.0%, GA=3.0%, AA=0% and GG=94.0%, GA=0%, AA=0%, respectively. In the case group, the allelic distribution was as follows: G=98.5%, A=1.5%. In the control group, the A allele was absent, and the frequency of the G allele was 100%. For the MTHFR C677T, the genotypic and allelic frequencies in the case group were 97%, 3%, and 0%, respectively, for the CC, CT, and TT genotypes, and 98.5% and 1.5%, respectively, for the C and T alleles. In the control group, the genotype distribution was as follows: CC-100% CT-0%, TT-0%; the T allele was absent, and the frequency of the C allele was 100%. For the FVL G1691A, the genotype distribution in the case group and control group was as follows: GG=92.0%, GA=8.0%, AA=0% and GG=93.6%, GA=6.4%, AA=0%, respectively. For G and A alleles, the frequencies were 96.0% and 4.0%, respectively, for the case group, and 96.8% and 3.2%, respectively, for the control group. Our analysis did not reveal a significant positive association between the MTHFR C677T, FII G20210A, and FVL G1691A polymorphisms and the risk of RPL across the dominant model, multiplicative model, and a comparison of the frequencies of the heterozygous and homozygous dominant genotypes. Conclusion: The research findings suggest that the MTHFR C677T, FVL G1691A, and FII G20210A variants do not significantly contribute to the increased susceptibility to RPL in this specific population of Sudanese women. Continued scientific inquiry is crucial for developing more nuanced and personalized strategies for the diagnosis and prevention of RPL, ultimately improving women's reproductive health.

Although para-aminosalicylic acid (PAS) has been used to treat tuberculosis for decades, mechanisms of resistance to this drug in Mycobacterium tuberculosis (M. tuberculosis) clinical isolates have not been thoroughly investigated. Previously, we found that decreased methylenetetrahydrofolate reductase (MTHFR) activity of Rv2172c led to increased sensitivity to antifolates in M. tuberculosis. In this study, we collected the genome-sequencing data of 173 PAS-resistant and 803 PAS-sensitive clinical isolates and analyzed rv2172c mutations in those 976 isolates. The results showed that two mutations (T120P and M172V) on rv2172c could be identified in a certain proportion (6.36%) of PAS-resistant isolates. The results of AlphaFold2 prediction indicated that the T120P or M172V mutation might affect the enzymatic activity of Rv2172c by influencing nicotinamide adenine dinucleotide (NADH) binding, and this was verified by subsequent biochemical analysis, demonstrating the role of residues Thr120 and Met172 on NADH binding and enzymatic activity of Rv2172c. In addition, the effect of rv2172c T120P or M172V mutation on methionine production and PAS resistance was determined in M. tuberculosis. The results showed that both T120P and M172V mutations caused increased intracellular methionine concentrations and high level PAS resistance. In summary, we discovered new molecular markers and also a novel mechanism of PAS resistance in M. tuberculosis clinical isolates and broadened the understanding of the NADH-dependent MTHFR catalytic mechanism of Rv2172c in M. tuberculosis, which will facilitate the molecular diagnosis of PAS resistance and also the development of new drugs targeting Rv2172c.

Liver serves as a hub for key metabolic pathways such as folate cycle that provides one-carbon units for a network of metabolic reactions. Methylenetetrahydrofolate reductase (MTHFR) is a rate limiting enzyme in folate metabolism and thus it is vital for DNA methylation, synthesis and repair [1]. The objective of this study was to evaluate an eventual association between MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) and the susceptibility to hepatocellular carcinoma (HCC) in Egyptian population. Blood samples from patients and controls from Mansoura university hospital were used after signed consent and approval from Medical ethical committee. The two genetic loci were designed for amplification and genotyped by using PCR–RFLP. Our results clarify that, the most important predictors for HCC are T/T genotype of variant C677T and C/C genotype of variant (A1298C) with odds ratio 3.28 and 2.99 respectively. Also, MTHFR variant C677T genotype C/C or T/T combined with MTHFR variant A1298C genotype C/C were associated with an increased risk of HCC, with the OR, 2.6 and 7 respectively. CT genotype of MTHFR variant C677T showed significant difference between HCC grades and C allele of variant C677T showed significant difference in BCLC stages of HCC. Our data indicates that, the two variants (C677T and A1298C) constitute a risk factor for the development of HCC and this could be attributed to the low activities of the enzyme MTHFR that disturb one carbon metabolism and subsequently, DNA synthesis, repair and methylation, thus cellular redox state, growth, and proliferation. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the methylenetetrahydrofolate reductase (MTHFR) 677 C > T gene polymorphism in term infants born small (SGA), appropriate (AGA), and large for gestational age (LGA). The study comprised 165 newborns with SGA, LGA and AGA. Genomic DNA was isolated from the peripheral blood. Samples were genotyped for MTHFR 677 C > T gene polymorphisms using PCR-RFLP. There was a statistically significant difference between the genotype and their allelic distribution of AGA, SGA, and LGA. The newborns carrying the TT genotype had higher birth weight than those carrying the CC and CT genotypes. The frequency of MTHFR 677 TT genotype and T allele was significantly higher and was found to be linked with a higher risk in LGA than in the AGA group. The MTHFR 677 C > T gene polymorphism can be used as a genetic marker in Turkish LGA newborns, but not in SGA. [ABSTRACT FROM AUTHOR]

This study focused on the link between skin disorders and Methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Study cases were taken from a pre-conceptional care program where patients with poor obstetric history were evaluated in terms of systemic disorders including skin diseases. This retrospective cohort (n = 472) consisted of 110 (23.3%) and 362 (76.7%) women with or without skin disorders, respectively. For ease of analysis, the history of skin diseases was classified into seven categories: (1) acne/rosacea/other acneiform disorders; (2) fungal disease; (3) pruritis/xerosis; (4) psoriasis vulgaris; (5) acrochordons and other benign skin growths; (6) urticaria/dermatitis; and (7) viral diseases. In this retrospective cohort of 472 women, we explored the impact of MTHFR A1298C and C677T polymorphisms on skin disorders. Despite similar allelic frequencies, our findings revealed a statistically significant association between the presence of MTHFR polymorphisms and skin disorders (p =.027). Subgroup analysis indicated significantly higher rates of MTHFR polymorphisms in patients with psoriasis vulgaris (p =.033) and acrochordons (p =.030), highlighting their potential relevance in specific skin disorder subtypes. The increased prevalence of psoriasis and acrochordons among women with MTHFR deficiency underscores the complex relationship between genetic factors and dermatological health. Our findings emphasized the critical role of MTHFR polymorphisms not only in poor obstetric history but also as significant contributors to skin disorders. This dual association highlights the importance of comprehensive preconception counseling, especially customized for women affected by skin disorders. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype. Materials and Methods: A prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5‐methyltetrahydrofolate (5‐MTHF), 5, 10‐methylene‐tetrahydrofolate (5,10‐CH2‐THF), 5‐ formyltetrahydrofolate (5‐CHO‐THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5‐MTHF, and methylmalonic acid (MMA), were determined at 6–17 weeks and 20–26 weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28 weeks of pregnancy by a 75‐g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders. Results: The study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI]) = 1.36 (1.01–1.84)], UMFA ≥ P90 [aOR (95% CI) = 1.82 (1.23–2.69)], and HCY ≥ P75 [aOR (95% CI) = 1.40 (1.04–1.88)] in early pregnancy, and RBC 5‐MTHF [aOR (95% CI) = 1.48 (1.10–2.00)], RBC 5,10‐CH2‐THF [aOR (95% CI) = 1.55 (1.15–2.10)], and plasma 5‐MTHF [aOR (95% CI) = 1.36 (1.00–1.86)] in mid‐pregnancy ≥ P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1‐h and 2‐h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5‐ MTHF and 5,10‐CH2‐THF, and plasma 5‐ MTHF in mid‐pregnancy are positively associated with the 1‐h glucose level (p < 0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM. Conclusions: Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5‐MTHF and 5,10‐CH2‐THF and plasma 5‐MTHF during mid‐pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM. [ABSTRACT FROM AUTHOR]

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

Aim: As the results of pharmacogenetic studies are increasingly translated into clinical practice, the ultimate goal of personalising treatment for children with cancer seems achievable in the future. Our survey aimed to establish to what extent pharmacogenetics has already been utilised in everyday work. Methods: A retrospective survey on pharmacogenetic testing in children treated for malignancies at the Department of Oncology and Haematology, Children's Hospital Zagreb, from 2021 to 2023 was carried out. Results: Pharmacogenetic testing was performed in 17.2% of the 180 children (53.3% female, median age 7.0 years), the greatest number of tests obtained in 2023. Preemptive testing included thiopurine S-methyltransferase polymorphisms (in 94.4% of children with acute lymphoblastic leukaemia and 33.3% with eosinophilic granuloma) and methylenetetrahydrofolate reductase gene polymorphisms assaying (in 55.6% of acute lymphoblastic leukaemia and 23.1% of osteosarcoma patients). In 8 children, pharmacogenetic testing was made due to adverse events (25% lung and 75% liver injury, all grade 4), in the majority of cases presumably related to vincristine. Pharmacogenetic testing results were pathological in all reactively tested patients, requiring dose modification/chemotherapeutics omission in 87.5% of cases. Conclusion: The number of pharmacogenetic assays performed due to high-grade adverse events in children with cancer has been continuously rising, steering otherwise standardised treatment towards a more individualised approach. Preemptive thiopurine Methyltransferase Polymorphism testing has been routinely done in almost all patients planned to receive thiopurines. However, more research is needed on drug-gene pairs in the field of paediatric oncology to minimise treatment-related toxicity and optimise treatment outcomes. [ABSTRACT FROM AUTHOR]

Funicular myelosis (subacute combined degeneration) is a disease characterized by the development of degeneration of the posterior and lateral cords of the spinal cord. Funicular myelosis is a neurological complication of vitamin B12 deficiency, which occurs as a result of reduced intake of vitamin B12 with food, malabsorption, in connection with taking some drugs (metformin, proton pump inhibitors, and nitrous oxide), with invasion by Diphyllobothrium latum. The disease is usually characterized by the presence of paresthesias, the development of sensitive ataxia, and impaired gait. The aim of the work was to demonstrate a clinical case of funicular myelosis in a young patient in order to improve the diagnostic process, paying attention to the genetic profile and identifying a concomitant predisposition to folate cycle disorder. A clinical case of funicular myelosis in a 39-year-old woman is described. The patient came to the neurology department with complaints of numbness in the upper and lower limbs, periodic shooting pains along the spine when the head is tilted forward. During the neurological examination, the following was observed: a decrease in vibrational, muscle-joint, discrimination sensitivity in the upper limbs, paresthesias in the distal parts of the limbs, and sensitive ataxia. According to the results of the magnetic resonance imaging (MRI) of the spinal cord, a lesion of the posterior cords on the long segment (C2-Th1) was found, which corresponds to the subacute degeneration of the spinal cord, which arose due to the deficiency of holotranscobalamin (active B12). The patient received appropriate treatment and was discharged home. Subsequently, the patient was found to have a concomitant genetic predisposition to folate cycle disorder and the development of thrombophilia. A year later, the woman again came to the neurological department. We carried out a repeated examination, evaluation of the results of the MRI of the cervical spine and other examinations in dynamics. According to the results of the literature analysis, additional markers for the diagnosis of funicular myelosis (in particular, homocysteine), the causes of hyper-homocysteinemia and its effects on the body were described. Timely detection and treatment of vitamin B12 deficiency is quite important, since in severe cases the development of spastic paraplegia is possible. Recovery of lost functions depends on the extent of spinal cord damage and the duration of the disease. If anemia is observed together with neurological symptoms, it is necessary to be especially attentive to possible funicular myelosis and to carry out appropriate diagnostic searches. And when detecting hyper-homocysteinemia, it is advisable to take into account other factors that can cause an increase in the level of homocysteine, in addition to a deficiency of vitamins B6, B12 and folic acid. [ABSTRACT FROM AUTHOR]

Background and purpose: The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in directing folate species towards nucleotide synthesis or DNA methylation. The MTHFR polymorphisms C677T and A1298C have been linked to cancer susceptibility, but the evidence supporting this association has been equivocal. To investigate the individual and joint associations between MTHFR C677T, A1298C, and digestive system cancer in a Chinese hypertensive population, we conducted a population-based case–control study involving 751 digestive system cancer cases and one-to-one matched controls from the China H-type Hypertension Registry Study (CHHRS). Methods: We utilized the conditional logistic regression model to evaluate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of digestive system cancer. Results: The analysis revealed a significantly lower risk of digestive system cancer in individuals with the CT genotype (adjusted OR: 0.71; 95% CI 0.52, 0.97; P = 0.034) and TT genotype (adjusted OR: 0.57; 95% CI 0.40, 0.82; P = 0.003; P for trend = 0.003) compared to those with the 677CC genotype. Although A1298C did not show a measurable association with digestive system cancer risk, further stratification of 677CT genotype carriers by A1298C homozygotes (AA) and heterozygotes (AC) revealed a distinct trend within these subgroups. Conclusion: These findings indicate a potential protective effect against digestive system cancer associated with the T allele of MTHFR C677T. Moreover, we observed that the presence of different combinations of MTHFR polymorphisms may contribute to varying susceptibilities to digestive system cancer. [ABSTRACT FROM AUTHOR]

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Background and Objectives: This retrospective cohort study investigates the role of genetic thrombophilia in pregnant women experiencing early pregnancy loss compared to those with late pregnancy loss. Materials and Methods: Participants were categorized into early and late pregnancy loss groups based on gestational age. A total of 156 patients were included, out of which 103 had early-trimester pregnancy losses and 96 had multiple miscarriages. Results: The study revealed a synergistic effect of Factor V Leiden (FVL G1691A) and Methylenetetrahydrofolate Reductase (MTHFR C677T) mutations (coefficient 3.42). Prothrombin (PT) G20210A and β-Fibrinogen 455 G>A mutations exhibited a significant interaction (coefficient 1.98). Additionally, MTHFR A1298C and Plasminogen Activator Inhibitor-1 (PAI-1 4G/5G) mutations showed a significant interaction (coefficient 1.65). FVL G1691A and Endothelial Protein C Receptor (EPCR) allele A1/A2 mutations also demonstrated a significant association (coefficient 2.10). Lastly, MTHFR C677T and Glycoprotein IIb/IIIa T1565C mutations interacted significantly (coefficient 1.77). Risk factor analysis identified several mutations associated with early pregnancy loss, including PAI-1 4G/5G homozygous (OR 3.01), FVL G1691A heterozygous (OR 1.85), and MTHFR A1298C heterozygous (OR 1.55). Both homozygous and heterozygous MTHFR C677T mutations were significant risk factors (OR 2.38; OR 2.06), as was PT G20210A homozygous mutation (OR 1.92). The PAI-1 4G/4G homozygous variant posed a risk (OR 1.36). Late pregnancy loss was associated with MTHFR A1298C homozygous mutation (OR 3.79), β-Fibrinogen 455 G>A heterozygous mutation (OR 2.20), and MTHFR A1298C heterozygous mutation (OR 2.65). Factor XIII G1002T heterozygous mutation (OR 1.18) and PAI-1 4G/5G homozygous mutation (OR 2.85) were also significant risk factors. EPCR allele A1/A2 (OR 1.60) and A2/A3 (OR 1.73) mutations were identified as significant risk factors for late pregnancy loss. Furthermore, FVL G1691A homozygous mutation, PT G20210A homozygous mutation, MTHFR C677T heterozygous mutation, MTHFR A1298C heterozygous mutation, and EPCR allele A1/A2 were identified as significant risk factors for multiple miscarriage. Conclusions: This study highlights significant interactions and risk factors related to genetic thrombophilia mutations in different types of pregnancy loss, contributing valuable insights for miscarriage management guidelines. [ABSTRACT FROM AUTHOR]

Background: Adiponectin and leptin are pivotal in the regulation of metabolism. Pediatric lupus nephritis (pLN), a manifestation of childhood systemic lupus erythematosus (SLE) affecting the kidneys, is associated with impaired adipokine levels, suggesting a role in pLN pathogenesis. The aim of this study was to explore the potential relationship between specific single-nucleotide polymorphisms (SNPs)—methylenetetrahydrofolate reductase (MTHFR) rs1801131 and fibrinogen gamma chain (FGG) rs2066865—and the serum levels of leptin and adiponectin in patients with pLN. Methods: Ninety-eight pLN patients and one hundred controls were enrolled in the study. Serum leptin and adiponectin levels were measured using ELISA. DNA extraction and real-time PCR genotyping were performed for MTHFR rs1801131 and FGG rs2066865 SNPs. Results: Compared to healthy controls, pLN patients exhibited significantly greater serum leptin (11.3 vs. 18.2 ng/mL, p < 0.001) and adiponectin (18.2 vs. 2.7 ug/mL, p < 0.001). Adiponectin levels were positively correlated with proteinuria (p < 0.05), while leptin levels positively correlated with proteinuria, SLE disease activity index-2000 (SLEDAI-2K), and cyclophosphamide usage (all p < 0.05). There was no significant association between MTHFR rs1801131 or FGG rs2066865 SNPs and pLN in either codominant or allelic models (all p > 0.05). However, the AG genotype of FGG gene rs2066865 SNP was significantly associated with high leptin levels (> 15 ng/mL) (p = 0.01). Conclusion: Serum adiponectin and leptin levels are associated with pathological manifestations of pLN. High leptin levels are associated with the AG genotype of FGG rs2066865 SNP in pLN patients, suggesting direct involvement in disease progression and potential utility as a disease biomarker. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: The role of maternal genetic factors in the association between high glycated haemoglobin (HbA1c) levels and adverse birth outcomes remains unclear. Materials and Methods: 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. Results: 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 0.11 weeks (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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15–5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.

The article explores the concept of embolic stroke of undetermined source (ESUS) and the role of genetic factors in ESUS patients. ESUS is diagnosed when a stroke occurs without a clear cause. Genetic variants, such as SERPINE1 and MTHFR, are being studied as potential determinants of ESUS. The article discusses the associations between these variants and increased stroke risk, as well as their implications for prevention and treatment. Additional research is needed to fully comprehend the prevalence and impact of these genetic variants in ESUS patients. The document also provides a list of references to scientific articles covering various topics related to stroke and thrombophilia, offering valuable information for researchers and those interested in understanding the mechanisms and risk factors associated with stroke and thrombophilia. [Extracted from the article]

Recently, molecular genetic studies have become widespread, and demonstrated the importance of DNA and histone methylation processes in the epigenetic regulation of gene expression. The aim of this study was to detect the association of polymorphisms of the folate cycle enzyme gene methylenetetrahydrofolate reductase (MTHGFR) with the degree of cognitive and affective disorders and the serum level of homocysteine and folic acid in 41 post-covid patients. Hematological and laboratory indices, serum concentration of C-reactive protein, D-dimer, homocysteine and folic acid were determined. MTHGFR polymorphisms for C677T and A1298C mutations were determined by polymerase chain reaction in real time. According to the MTHGFR C677T genotype variant, the examined patients were divided into 3 groups: 1) 21 persons (male/female 10/11) with homozygous CC genotype; 2) 17 ones (male/female 12/5) with heterozygous CT genotype; 3) 3 persons with a recessive homozygous TT genotype (all men). Six months after the end of the acute phase of the coronavirus disease, patients were surveyed using questionnaires to assess the psycho-emotional state: cognitive function, anxiety and depression. No significant difference was found in the average scores of cognitive function, anxiety and depression in patients of group 1 and 2. Individuals of the group 1 C677C, who had an additional recessive homozygous C1298C mutation (group 1a, n=6), were characterized by an elevated level of homocysteine, which showed a high negative correlation with serum folate (r= -0.95). A small group of individuals with the recessive homozygous T677T genotype (group 3, all men) was distinguished by an older age, the presence of cardiovascular diseases, type 2 diabetes (2 cases out of 3), more severe manifestations of COVID-19, which forces us to pay attention to potentially increased risk of complications in such patients and requires further investigation. Correlation relationships between assessments of cognitive function, anxiety, depression and serum levels of homocysteine and folate in patients with different genotypes of MTHGFR C677T were recorded. Therefore, the use of a molecular genetic approach made it possible to pay attention to the possible predisposition to hyperhomocysteinemia in individuals who have a folic acid deficiency, and different combination of alleles of the MTHGFR gene C677T and A1298C.

Dental caries (DC)-induced pulp infections usually undergo the common endodontic treatment, root canal therapy (RCT). Endodontically treated teeth are devitalized, become brittle and susceptible for re-infection which eventually results in dental loss. These complications arise because the devitalized pulp losses its ability for innate homeostasis, repair and regeneration. Therefore, restoring the vitality, structure and function of the inflamed pulp and compromised dentin have become the focal points in regenerative endodontics. There are very few evidences, so far, that connect methylenetetrahydrofolate reductase single nucleotide polymorphisms (MTHFR-SNPs) and dental disorders. However, the primary consequences of MTHFR-SNPs, in terms of excessive homocysteine and folate deficiency, are well-known contributors to dental diseases. This article identifies the possible mechanisms by which MTHFR-SNP-carriers are susceptible for DC-induced pulp inflammation (PI); and discusses a cell-homing based strategy for in vivo transplantation in an orthotopic model to regenerate the functional dentine-pulp complex which includes dentinogenesis, neurogenesis and vasculogenesis, in the SNP-carriers.

Objective To observe the gene polymorphism of methylenetetrahydrofolate reductase （MTHFR） C677T in patients with H-type hypertension combined with acute ischaemic stroke and to analyze its correlation with renal function in these patients. Methods Totally 153 patients with H-type hypertension combined with acute ischaemic stroke were selected as the observation group, and 158 patients with non-H-type hypertension combined with acute ischaemic stroke in the same period were selected as the control group. Peripheral venous blood was collected from both groups, and MTHFR C677T genotype was detected by PCR amplification and microarray technology to measure systemic immune inflammation index （SII), and serum creatinine levels were measured using a Hitachi 7600 automatic biochemical analyzer in order to calculate the estimated glomerular filtration rate （eGFR） in both group. Multiple linear regression analysis was employed to assess the correlations of MTHFR C677T genotypes with homocysteine （Hcy） level and eGFR in patients with H-type hypertension combined with acute ischaemic stroke, and Spearman correlation analysis was employed to assess the correlations of SII with eGFR and Hcy levels in patients with H-type hypertension combined with acute ischaemic stroke. Results Compared with the control group, patients in the observation group had the highest frequency of TT genotype distribution and the highest frequency of T allele （χ2 =19. 188, 5. 138, respectively； both P<0. 05). The SII of patients in the observation and control groups were 583. 54（384. 97, 903. 73） and 425. 03（310. 26, 583. 16), respectively, with statistically significant difference between these two groups （P<0. 05). TT genotype patients with H-type hypertension combined with acute ischaemic stroke had higher serum Hcy level and lower eGFR level than patients with CC and CT geno‐ types （F=28. 544, 3. 749, respectively； both P<0. 05). The TT type of MTHFR C677T gene was positively correlated with serum Hcy level in patients with H-type hypertension combined with acute ischaemic stroke （β=4. 173, P<0. 05） and was negatively correlated with eGFR level （β=-6. 559, P<0. 05). The SII was positively correlated with serum Hcy level （r =0. 226, P<0. 05） and was negatively correlated with eGFR level （r=-0. 129, P<0. 05） in patients with H-type hyperten‐ sion combined with acute ischaemic stroke. Conclusions Patients with H-type hypertension combined with acute isch‐ aemic stroke predominantly exhibit the TT genotype of the MTHFR C677T gene. It is suggested that patients with H-type hypertension combined with acute ischaemic stroke carrying the TT genotype of MTHFR C677T may be more prone to experiencing a decline in renal function. [ABSTRACT FROM AUTHOR]

Background: Considering 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 presentation: A 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. Conclusion: We 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. [ABSTRACT FROM AUTHOR]