Methylenetetrahydrofolate Reductase Research Articles

Molecular Mechanism Biomarkers Predict Diagnosis in Schizophrenia and Schizoaffective Psychosis, with Implications for Treatment.

Diagnostic uncertainty and relapse rates in schizophrenia and schizoaffective disorder are relatively high, indicating the potential involvement of other pathological mechanisms that could serve as diagnostic indicators to be targeted for adjunctive treatment. This study aimed to seek objective evidence of methylenetetrahydrofolate reductase MTHFR C677T genotype-related bio markers in blood and urine. Vitamin and mineral cofactors related to methylation and indolamine-catecholamine metabolism were investigated. Biomarker status for 67 symptomatically well-defined cases and 67 asymptomatic control participants was determined using receiver operating characteristics, Spearman's correlation, and logistic regression. The 5.2%-prevalent MTHFR 677 TT genotype demonstrated a 100% sensitive and specific case-predictive biomarkers of increased riboflavin (vitamin B2) excretion. This was accompanied by low plasma zinc and indicators of a shift from low methylation to high methylation state. The 48.5% prevalent MTHFR 677 CC genotype model demonstrated a low-methylation phenotype with 93% sensitivity and 92% specificity and a negative predictive value of 100%. This model related to lower vitamin cofactors, high histamine, and HPLC urine indicators of lower vitamin B2 and restricted indole-catecholamine metabolism. The 46.3%-prevalent CT genotype achieved high predictive strength for a mixed methylation phenotype. Determination of MTHFR C677T genotype dependent functional biomarker phenotypes can advance diagnostic certainty and inform therapeutic intervention.

Association between MTHFR gene C677T polymorphism and gestational diabetes mellitus in Chinese population: a meta-analysis.

The relationship of the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with the incidence of gestational diabetes mellitus (GDM) in the Chinese population remains controversial. This study aimed to further clarify the effect of the MTHFR gene C677T polymorphism on GDM risk among Chinese pregnant women based on current evidence. Several databases were searched up to July 29, 2023 for relevant case-control studies. The numbers of patients with and without the T allele of the MTHFR gene C677T polymorphism in the GDM and control groups were determined, and all statistical analyses were performed by RevMan 5.3 software and STATA 15.0 software. Trial sequential analysis (TSA) was performed by TSA version 0.9 beta software to determine the required information size. A total of 17 case-control studies involving 12345 Chinese participants were included. The pooled results demonstrated that the T allele of the MTHFR gene C677T polymorphism was significantly associated with an increased risk of GDM, which was manifested by the five gene models of the MTHFR C677T polymorphism [T vs. C: odds ratio (OR)=1.59, P=0.03; TT vs. CC: OR=2.24, P<0.001; TC vs. CC: OR=1.28, P=0.05; (TT+TC) vs. CC: OR=1.55, P=0.003; TT vs. (TC+CC): OR=1.89, P<0.001]. Subgroup analysis based on the regions indicated that the significant relationship between the T allele of the MTHFR gene C677T polymorphism and an increased risk of GDM was detected only among the southern population [T vs. C: OR=1.62, P=0.09; TT vs. CC: OR=2.22, P=0.004; TC vs. CC: OR=1.17, P=0.28; (TT+TC) vs. CC: OR=1.43, P=0.03; TT vs. (TC+CC): OR=1.97, P=0.006]. TSA plots showed that the information sizes for the association between the MTHFR gene C677T polymorphism and GDM risk were sufficient in the homozygote (TT vs. CC) and recessive (TT vs. TC+CC) models. The MTHFR gene C677T polymorphism is closely related to susceptibility to GDM in the southern Chinese population, and the C-T mutation serves as an important genetic risk factor for GDM. More well-designed large case-control studies are needed to further confirm the above findings.

MTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adults.

The relevance of folic acid for stroke prevention in low-folate populations such as in China is uncertain. Genetic studies of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which increases plasma homocysteine (tHcy) levels, could clarify the causal relevance of elevated tHcy levels for stroke, ischaemic heart disease (IHD) and other diseases in populations without folic acid fortification. In the prospective China Kadoorie Biobank, 156 253 participants were genotyped for MTHFR and 12 240 developed a stroke during the 12-year follow-up. Logistic regression was used to estimate region-specific odds ratios (ORs) for total stroke and stroke types, IHD and other diseases comparing TT genotype for MTHFR C677T (two thymine alleles at position 677 of MTHFR C677T polymorphism) vs CC (two cytosine alleles) after adjustment for age and sex, and these were combined using inverse-variance weighting. Overall, 21% of participants had TT genotypes, but this varied from 5% to 41% across the 10 study regions. Individuals with TT genotypes had 13% (adjusted OR 1.13, 95% CI 1.09-1.17) higher risks of any stroke [with a 2-fold stronger association with intracerebral haemorrhage (1.24, 1.17-1.32) than for ischaemic stroke (1.11, 1.07-1.15)] than the reference CC genotype. In contrast, MTHFR C677T was unrelated to risk of IHD or any other non-vascular diseases, including cancer, diabetes and chronic obstructive lung disease. In Chinese adults, the MTHFR C677T polymorphism was associated with higher risks of stroke. The findings warrant corroboration by further trials of folic acid and implementation of mandatory folic acid fortification programmes for stroke prevention in low-folate populations.

MTHFR mutation: Another unifying etiology of chronic overlapping pain conditions

Introduction and Objective:Chronic pelvic pain (CPP) is a heterogeneous condition with multiple etiologies. Better characterization and understanding of CPP will lead to new therapeutic options and individualization of care, especially in patients with chronic overlapping pain syndromes (COPCs), which increase complexity of diagnosis. In this study, we present 6 patients with COPC and complex CPP, non-focal exam, who tested negative for small fiber neuropathy but who reported a history of methylenetetrahydrofolate reductase (MTHFR) mutations, and retrospective review of 76 patients with MTHFR mutation. This study explores through literature review whether MTHFR mutations play a role in the pathogenesis of chronic pelvic pain and overlapping pain conditions in a subset of patients with COPCs. Methods:Study design included an observational study of 6 patients, a retrospective cross-sectional study of 76 patients, and a literature review. Patients at our institution who tested positive for MTHFR mutations were included in the study; most had been seen in the cardiology/hematology clinics due to the association of MTHFR with clotting disorders. Chart review was performed to identify the presence of pain syndromes and specifically CPP. A review of the literature was undertaken to form a hypothesis for mechanisms that could explain the association between MTHFR mutations and chronic overlapping pain syndromes. Results:Of 76 patients with MTHFR mutations seen primarily in non-pain focused cardiology visits, 30 (39%) had some form of pain syndrome documented, 11 of whom (14%) specifically had CPP. The review below suggests that MTHFR plays a role in the maintenance of nerve tissue and conductance, neural tube defects, and paresthesia. Literature review revealed that MTHFR mutations have been linked with chronic pain and pathological processes such as chronic migraine, interstitial cystitis/bladder pain syndrome, sequelae of chronic Lyme disease, and fibromyalgia. Conclusions:The etiology of chronic pelvic pain is complex. Multisystem pain extending beyond the pelvis complicates the differential diagnosis but suggests a systemic cause. MTHFR mutations may play a unifying role in a subset of chronic pelvic pain patients with concomitant chronic overlapping pain syndromes. The mutations may affect folate metabolism pathways in these patients and hinder the ability to maintain nerve fibers over time, leading to dereliction of pain signal conduction. Disturbance of these pathways may have a role in chronic overlapping pain syndromes and complex pelvic pain.

The role of hereditary thrombophilia in the development of venous thrombosis in combat trauma

Introduction. Combat trauma is one of the factors causing hemostasis disorders in the wounded. Currently, there is insufficient information about the significance of hereditary thrombophilia in the development of venous thromboembolic complications in the wounded.Aim. To study the effect of polymorphism of genes of components of the hemostasis system on the development of venous thrombosis in wounded with combat trauma.Materials and methods. The prospective study included men (n = 81) of young age (the average age was 36.0 ± 8.5 years) who received a combat wound and were treated at the Military Medical Academy named after S.M. Kirov. The subjects were divided into 2 groups: the main group included 40 victims (49.4%) who were diagnosed with venous thrombosis during treatment, the control group included 41 patients without signs of thrombosis (50.6%). The study of allelic polymorphism of genes associated with the formation of blood clots was carried out using a real-time polymerase chain reaction based on the study of human DNA in peripheral blood material.Results. Comparative analysis revealed no statistically significant differences in the frequency of occurrence of the studied genetic variants between the study group and the control group. When assessing the prevalence of polymorphism of the MTHFR and MTRR genes, it was found that the combination of the genotypes “MTHFR 677 CT” and “MTRR 66 GG” is associated with an 8.5-fold increase in the risk of developing VTEO [OR = 8.5; p = 0.029].Conclusion. Analysis of the test results showed that no relationship was found between individual genetic variants and the risk of developing venous thrombosis in the studied group of wounded despite the high prevalence (prothrombogenic alleles of various genes were detected in 79 servicemen (97.5%)). At the same time, the combination of MTHFR 677 CT and MTRR 66 GG genotypes in that patient population was shown to be associated with a significant increase in the risk of thrombosis.

Homozygous C677T Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism as a Risk Factor for Endometriosis: A Retrospective Case-Control Study.

This study was conducted to evaluate the role of methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism as a risk factor for endometriosis. A retrospective case-control study was conducted from January 2020 to December 2022 on all patients attending the gynecological outpatient clinic of our institution who had performed an MTHFR polymorphisms test. Patients with endometriosis were considered cases, while those without endometriosis were considered controls. The presence of an MTHFR C677T homozygous polymorphism was defined as exposure. Risk factors for endometriosis were considered confounders in a binomial logistic regression, with endometriosis diagnosis as the dependent variable. Among the 409 included patients, 106 (25.9%) cases and 303 (74.1%) controls were identified. A higher rate of MTHFR C677T homozygous polymorphism was found in patients with endometriosis (24.5% vs. 15.8%, p = 0.0453), with an adOR of 1.889 (95% CI 1.076-3.318, p = 0.0269) at the binomial logistic regression. A history of no previous pregnancy was associated with an endometriosis diagnosis (adOR 2.191, 95% CI 1.295-3.708, p = 0.0035). An MTHFR C677T homozygous polymorphism could be considered a risk factor for endometriosis. Epigenetic modifications may be the most important mechanism explaining the observed association through the processes of altered DNA methylation and reduced activity of antioxidant systems.

MTHFR, NR3C1, FKBP5, and CRHR1 gene polymorphisms are strongly associated with depressive disorder susceptibility: A meta-analysis and power analysis

Depression is a polygenic and complex condition; however, most genetic analyses have yielded insignificant associations between candidate genes and depressive disorder. This is primarily due to the lack of reproducible findings in genome-wide association studies (GWAS). In this meta-analysis, we extensively investigated the implications of genetic polymorphisms in seven candidate genes for depression. We conducted a thorough search of electronic databases, including Google Scholar, Cochrane, PubMed, Medline, Embase, and PsycINFO, covering data from January 1997 to 2022. Our search identified approximately 3,500 published research papers related to this study. Among these, 81 studies met our eligibility criteria and focused on the six genes under study. These selected candidate genes for our meta-analysis included NR3C1, MTHFR, FKBP5, CRHR1, COMT, and TNF-α. The results of our meta-analysis on genetic polymorphisms indicate a significant association with depression at the 95% confidence interval (CI). When categorizing outcomes by different ethnic groups, our findings reveal significant results (p=<0.05) for Asian and Caucasian populations. This current meta-analysis provides valuable insights that can facilitate the use of these significantly associated genes for diagnosing the severity of depression or as indicators for treatment modalities in depression conditions.

Anticancer Activity of Alangium Salvifolium on Human Breast Cancer Cell Lines MCF-7, MDA-MB-468

Alangium salvifolium is a plant that grows in the alangium family. The study's plant species were chosen.The present study was implemented for revealing the anticancer effect of the leaves of methanolic extract of Alangium salvifolium. Phytochemical Screening of A.Salvifolium leaf extract was done which showed the presence of Alkaloids, Flavonoids,Terpenoids. Human Breast Cancer cell lines MCF-7, MDA-MB-468 cells were grown in RPMI media and the 5-10- methylenetetrahydrofolate reductase (MTHFR) Enzyme inhibitory activity was investigated. MTHFR is a one-carbon metabolism enzyme that redirects the pool of folate from DNA synthesis and repair to methylation. The enzyme is vital for cellular homeostasis due to its key functions in the one carbon cycle,which include methionine and protein,DNA and RNA synthesis. Cancer cell lines MCF-7 and MDA-MB-468 treated with Alangium Salvifolium compounds AS1- Deoxytubulosine and AS2 - carboline Hermaline.

The importance of preconception Hcy testing: identification of a folate trap syndrome in a woman attending an assisted reproduction program.

Methylation is a ubiquitous and permanent key biochemical process playing a major role in gametogenesis and embryogenesis in relation to epigenetics and imprinting. Methylation relies on a unique cofactor S-Adenosyl Methionine: SAM. Release of the methyl group onto target molecules is followed by liberation of S-Adenosyl Homocysteine (SAH), and then homocysteine (Hcy), both potent inhibitors of the methylation process. Defective recycling of homocysteine, leading to Hyperhomocysteinemia, is mainly due to reduced activity of MTHFR (Methylene TetraHydroFolate Reductase). However, we described here, in a woman attending an ART program, arather rare syndrome: The Folate trap syndrome. Due to vitamin B12 deficiency (malabsorption), Hcy cannot be recycled to methionine by the methionine synthase. Transmethylation activity is weak and leads to Hhcy (Hyperhomocysteinhemia). Her Hhcy, over 16µM, was resistant to 5MTHF (5 Methyltetrahydrofolate) associated with a support of the one carbon cycle, a classical efficient treatment for elevated homocysteine. Treatment with Methylcobalamine (associated with adenosyl Cobalamine) allowed a Hcy drop down to 10 µM. Knowing the pleiotropic negative impact of Hcy on gametes, embryos and pregnancy in general, we strongly recommend a Hcy dosage in both members of couples seeking treatmentfor pregnancy.

Genetic variants of MTHFR gene in relation to folic acid levels and bone mineral density in Polish patients with inflammatory bowel disease

Lower bone mineral density (BMD) constitutes a common issue in inflammatory bowel disease (IBD). Studies often explore the association between BMD and folic acid level. The presented study aimed to evaluate the impact of MTHFR gene polymorphism and folic acid levels on BMD in patients with IBDs: Crohn’s disease (CD) and ulcerative colitis (UC). The study group comprised IBD patients and a healthy control group. BMD, T-score, and Z-score of the lumbar spine (L1-L4) and femoral neck (FN) were assessed using dual-energy X-ray absorptiometry. Folic acid level was determined using direct chemiluminescence, and the MTHFR 677C > T (rs1801133) and 1298A > C (rs1801131) genotyping were performed by HRMA. Our study found no significant differences in the folic acid levels between the groups. Patients with CD and UC presented a lower BMD, T-score, and Z-score of the FN and L1-L4 than the CG. UC patients who were homozygotes AA in loci c.1298A>C presented lower than controls lumbar spine L1-L4 BMD and T-score values. Regarding MTHFR 677 polymorphism, we found that IBD patients carrying CC genotype demonstrated lower than controls femoral neck Z-score, lumbar spine L1-L4 BMD, T-score and Z-score. MTHFR polymorphisms were found to have no impact on folic acid concentrations. IBD patients presented a higher risk of low BMD than the healthy controls, regardless of MTHFR 677 and 1298 genotypes. However, MTHFR polymorphism may influence on bone in IBD patients. Nevertheless, it appears essential to conduct further studies.

Vitamin B6, Magnesium, and Vitamin D: The Triple Play

Vitamin B6, magnesium, and vitamin D are important antioxidants. Mg is a required cofactor for the synthesis of vitamin D and the active forms of vitamins B1,2,3,5,6,9,12 (seven of the eight B vitamins). Five of the seven (and magnesium) are critical to the methylation cycle, compromised by MTHFR (methylene tetrahydrofolate reductase) variants, present in the majority of Caucasians and Asians. Homocysteine (Hcy), a powerful pro-oxidant, is upregulated in these variants. Oxidative stress compromises mitochondrial function, required for the synthesis of the active form of vitamin D. Pyridoxal phosphate (P5P or PLP), the active form of B6, enhances the intracellular entry of magnesium and is required for the synthesis of the antioxidants melatonin and glutathione, oft called the “mother” of all antioxidants. Deficiencies of P5P and vitamin D are associated with decreased gut microbiota diversity and short chain fatty acids, e.g., butyrate, as seen in Long Covid (LC) and Chronic Fatigue Syndrome (CFS). This suboptimal gut microbiome reflects the continuing decline in the nutritional value of the Western diet. The interdependencies of and associations between P5P, magnesium, and 1,25(OH)2D, the active form of vitamin D, are explored.

Ischemic cerebrovascular disease caused by genetic mutation and patent foramen ovale

Abstract Objectives The search for genetic mutations is very important in younger patients and other age groups with a history of recurrent cerebrovascular diseases (CVD) and a family history of other causes to be excluded. The aim of this study is to define the characteristics of genetic mutations in the etiology of ischemic stroke. Methods Twenty-three patients with acute CVD in the last 1 year and only genetic mutations acknowledged in the etiology were retrospectively analyzed. We determined the frequency of the genetic mutations that are observed in cerebral arterial events (CAE) and cerebral venous thrombosis (CVT). Results All patients had at least one genetic mutation and 19 of them had arterial events and 4 had venous thrombosis. MTHFR mutation was the most common mutation and PAI-1 mutation was the second in line for the arterial events. PAI 4G/5G, MTHFR A1298 and FV mutations were most frequently observed in venous events. Patent foramen ovale (PFO) was detected in 14 patients (%74) with CAE. Conclusions We concluded that multiple gene mutations may significantly increase the development of CVD. CVD is most commonly associated with MTHFR, PAI-1 or FV gene mutations and is most commonly seen in CAE. MTHFR mutations showed moderate linear correlation in the development of arterial events and FXII and FXIII mutations in venous events. The association of thrombophilia and PFO is high in patients who have undergone CAE, especially responsible for recurrent events. This study will need to be confirmed by prospective studies with larger sample and control group.

Identification of a Potential Antimycobacterial Drug Sensitizer Targeting a Flavin-Independent Methylenetetrahydrofolate Reductase.

The increasing antibiotic resistance of Mycobacterium tuberculosis and pathogenic nontuberculosis mycobacteria highlights the urgent need for new prevention and treatment strategies. Recently, the cocrystal structure of a Mycobacterium smegmatis flavin-independent 5,10-methylenetetrahydrofolate reductase (MsmMTHFR) that binds with a reduced nicotinamide adenine dinucleotide (NADH) has been well-determined, providing a structural basis for the screening of antimycobacterial leads targeting MsmMTHFR, a new enzyme involved in tetrahydrofolic acid (THF) biosynthesis. In this study, we identified compound AB131 as a promising candidate that fits well into the NADH binding pocket of MsmMTHFR through virtual screening. We discovered that AB131 and its derivatives (13 and 14) can sensitize the antimycobacterial activity of the antitubercular drug para-aminosalicyclic acid (PAS) by 2-5-fold against various species of mycobacteria. Although the compounds themselves do not exhibit any antimycobacterial activity, the high binding affinity of AB131 with MsmMTHFR or Rv2172c was evaluated by microscale thermophoresis analysis. Additionally, we predicted and validated the key residues (V115, V117, P118, and R163) of MsmMTHFR that are involved in the interaction with AB131 by using molecular docking and mutagenesis analysis. These findings offer a potential exploitable target for developing potent and specific antimycobacterial drug sensitizers.

Relationship between the methylenetetrahydrofolate reductase (MTHFR) rs1801133 SNP and serum homocysteine levels of Zhuang hypertensive patients in the central region of Guangxi

BackgroundThe relationship between the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphism (SNP) and serum homocysteine (Hcy) levels or H-type hypertension in different populations is inconsistent. This study aimed to explore the association between the MTHFR rs1801133 SNP and serum Hcy levels of Zhuang hypertensive patients in the central region of Guangxi.MethodsA total of 606 Zhuang inpatients with essential hypertension were recruited in our hospital from August 2016 to December 2018. The patients were divided into H-type hypertension (Hcy > 10 µmol/L, n = 528) and non–H-type hypertension (Hcy ≤ 10 µmol/L, n = 78) groups. At the same time, an age- and sex-matched group of 379 subjects with normal physical examination in our hospital were selected as the control group. Blood biochemical measurements and genotyping of the MTHFR rs1801133 SNP were performed.ResultsThe prevalence of H-type hypertension was 87.13%. The levels of serum Hcy in patients with hypertension were higher than those in control group (14.20 ± 5.78 μmol/L vs. 11.97 ± 5.39 μmol/L, P < 0.001), especially in patients with H-type hypertension (15.08 ± 5.65 μmol/L, P < 0.001). The frequencies of TT genotype (22.73%) and T allele (46.21%) in patients with H-type hypertension were significantly higher than those in control group (11.35% and 30.47%, respectively) and non–H-type hypertension group (10.26% and 28.85%, respectively; P < 0.001 for all). Multivariate linear regression analysis showed that serum Hcy levels were significantly correlated with creatinine, low-density lipoprotein cholesterol, endogenous creatinine clearance rate, and the MTHFR rs1801133 genotypes in control group, while serum Hcy levels were significantly correlated with creatinine, triglyceride, low-density lipoprotein cholesterol, endogenous creatinine clearance rate, glycosylated hemoglobin, and the MTHFR rs1801133 genotypes in H-type hypertension group (P < 0.05–0.001). Serum Hcy levels in the T allele carriers were higher than those in the T allele noncarriers in both H-type hypertension and control groups.ConclusionsThere was closely related between the MTHFR rs1801133 SNP and serum Hcy levels in Zhuang patients with H-type hypertension in the central region of Guangxi. The MTHFR SNP may be an important reason for the increase of serum Hcy levels in Zhuang patients with H-type hypertension in this region.

Detection of Methylene Tetrahydrofolate Reductase (MTHFR C677T) Mutation among Acute Lymphoblastic Leukemia in Sudanese Patients.

A genetic polymorphism that causes abnormal folate metabolism may lead to genomic instability and increase susceptibility to malignancies such as Acute Lymphoblastic leukemia (ALL). The purpose of this research is to identify methylene tetrahydrofolate reductase (MTHFR C677T) (NCBI ID: 4524) mutation in ALL patients. The study was a descriptive case-control hospital-based study with one hundred Sudanese participants divided equally into fifty (50) Sudanese ALL diagnosed patients as cases and fifty (50) Sudanese individuals as controls. The MTHFR C677T mutant allele was detected using conventional PCR, with the primer sequence of MTHFR C677T F-TGAAGGAAGGTGTCTGCGGGA R-AGGACGGTGCGGTGAGAGTG. The study was conducted from January to March 2023, and samples were collected from the Radiation and Isotops Center at Khartoum Hospital. The investigation revealed that 12 of the 50 patients in the case group (24%) had the MTHFR C677T mutant allele, and the study also revealed that there is significant correlation with the control group. There is no significant relationship between socio-demographic variables and MTHFR mutation detection in ALL patients. Also, the sociodemographic variables predictors of MTHFR mutation among ALL patients adjusted for smoking habit revealed no significant relationship. According to the findings of this study, the mutant allele of the Methylene Tetra Hydro Folate Reductase C677T was detected and demonstrated varying degrees of significance. It was concluded that the MTHFR C677T gene mutation was associated with acute lymphoblastic leukemia in Sudanese patients.

The role of methylenetetrahydrofolate reductase gene polymorphisms hypercoagulable status of coronavirus disease

Abstract Background: Hypercoagulation is a hallmark in coronavirus disease (COVID-19). The activity of the enzyme methylenetetrahydrofolate reductase (MTHFR) determines homocysteine levels, and polymorphisms in the enzyme’s gene can influence the enzyme activity with a consequence of hypercoagulability in patients with COVID-19. Objectives: To investigate the association of two single nucleotide polymorphisms (SNPs) in the MTHFR gene with hypercoagulability status in COVID-19. Materials and Methods: This is a retrospective cross-sectional study, which included 90 patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with variable severity. Patients were classified according to D-dimer level at admission into two groups: with and without hypercoagulability. Nucleic DNA was extracted from leukocytes and gene fragments corresponding to C677T and A1298C MTHFR gene were amplified and genotyped using allele specific polymerase chain reaction. Results: Hypercoagulation was reported in 42.22% of the patients. The mutant homozygous genotype (TT) was more frequent among hyper - than normocoagulable patients (13.6% vs. 1.92%) with a significant difference (odds ratio [OR] = 9.28, 95% confidence interval [CI] = 1.02–84.78, P = 0.048). Furthermore, T allele was more common among hyper- than normocoagulable patients (28.95% vs. 13.46%) with a significant difference (OR = 2.62, 95% CI = 1.24–5.5, P = 0.012). In contrast, the SNP A1298C had no significant impact. Conclusions: The TT genotype and T allele of C677T polymorphism but not A1298C in cMTHFE gene could be considered a risk factor for the hypercoagulable status in COVID-19.

Investigating the Association of MTHFR C677T Gene Polymorphism with Recurrent Spontaneous Abortion Among Azerbaijani Women from Northwest Iran.

Background: Recurrent spontaneous abortion (RSA), defined as two or more succeeding abortions during 20 weeks of gestation, affects 3-5% of pregnancies. Several studies have found that most women with RSA had at least one (and sometimes two copies) of the methylenetetrahydrofolate reductase (MTHFR) C677T variant. Materials and Methods: The study involved 118 women who had two or more spontaneous abortions (SAs) as the case group and 118 women who had at least one live birth but no SA as the control group. Clinical features such as age, body mass index (BMI), medication received, family history of abortion, and thrombophilia were investigated. Real-time PCR was used for genotyping subjects for MTHFR C677T gene polymorphism. Results: Significant differences in age, BMI, and medication received characters have been shown between those in the patients' group. For the MTHFR C677T gene, the genotypes for the patients' group were 36%, 60%, and 4%, whereas the genotypes for the control group were 30%, 58%, and 12%. In addition, the C and T allelic frequencies were 59% and 41% in the healthy control group and 67% and 33% in the patients' group, respectively. A significant association was found between the TT genotype and RSA. A 3.84-fold increased risk of RSA was associated with the TT genotype (odds ratio = 3.84, confidence interval: 1.28-10.93, p-value = 0.02). Conclusions: In this study, homozygosity for the T allele was significantly lower in the RSA-affected than in healthy women, whereas heterozygosity did not vary substantially between the two groups, which was in line with other studies.

Baş boyun kanserli hastalarda tek gen polimorfizmi ile sisplatin ve 5-FU tedavisine yanıt arasındaki ilişki

Amaç: Baş ve boyun kanserleri dünya çapında en sık görülen altıncı kanser türüdür. Baş ve boyun kanserlerinin tedavi süreci kemoterapi veya kemoradyoterapi olarak sınıflandırılır. Bu çalışmada ERCC1, XRCC1 ve MTHFR genlerinin tedavi ile yanıt ilişkisi araştırıldı.&#x0D; Gereç ve Yöntemler: Çalışmada tek nükleotid polimorfizmini araştırmak amacıyla hastalardan 5 ml kan alınarak DNA izole edildi ve pirosequencing yöntemiyle araştırıldı.&#x0D; Bulgular: Hastalar RECIST kriterlerine göre değerlendirildi; tedaviden önce (4 hafta) ve her üç siklustan sonra baş ve boyun bilgisayarlı tomografi taramaları yapıldı. Genel yanıt oranı (RR) 10 (%25) PD, 7 (%17,5) SD, 9 (%22,5) PR ve 14 (%35) CR idi. En az bir polimorfik varyantı olan hastaların dördünde PD, 3'ünde SD, 3'ünde PR ve 1'inde CR vardı.&#x0D; Sonuçlar: Bu çalışmada bir grup baş boyun karsinomu hastasının klinik davranışı, üç tek nükleotid polimorfizmi ile ilişki açısından retrospektif olarak değerlendirildi. Bunlar arasında ERCC1 geninde C8092A, XRCC1 geninde G28152A ve MTHFR geninde C677T ve A1298C yer alıyordu.

THE CONTENT OF ENDOTHELIN-1 IN THE BLOOD PLASMA OF PATIENTS WITH DIABETIC RETINOPATHY ON THE BACKGROUND OF TYPE 2 DIABETES DEPENDING ON THE POLYMORPHIC VARIANTS OF THE MTHFR, MTRR AND MTR GENES

Backround. The vascular and extravascular microcirculation of the eye is a rich source of endothelin-1 (ET-1), which can contribute to abnormal retinal hemodynamics in diabetic retinopathy. In patients with type 2 diabetes mellitus (T2DM), an increase in the level of circulating ET-1 was found, and a positive correlation between its levels in the blood was found and degree of microangiopathy. Strengthens the development of endothelial dysfunction and microvascular complications, a high level of homocysteine, which occurs due to a genetically determined deficiency of enzymes of the folate cycle, determines in the body what, because homocysteine ​​causes a violation of the structure of endothelial cells.&#x0D; Aim: to study the ET-1 content in the blood plasma of patients with diabetic retinopathy against the background of type 2 diabetes, depending on the polymorphic variants of the MTHFR, MTRR and MTR genes, as an important pathogenetic pathway for the development of endothelial dysfunction.&#x0D; Materials and methods. The study included 83 patients (83 eyes) with T2DM, in whom non-proliferative and proliferative DR were found according to the results of an ophthalmological examination using the ETDRS scale. The control group (CG) included 35 people without diabetes, who were matched with patients by gender, age, and body mass index. Gene polymorphism was determined using real-time PCR on the automatic amplifier Gene Amp® PCR System 7500, the content of ET-1 was determined in blood plasma by the ELISA method.&#x0D; Conclusion. The SS genotype of the rs1801133 gene, the GG genotype of the rs1805087 gene, the AS polymorphism, and the SS genotype of the rs1801131 gene can be considered potential risk factors for the development of DR on the background of type 2 diabetes.&#x0D; The SS genotype of the rs1801133 gene was accompanied by a maximum 14-fold increase in ET-1 in patients with DR. The minor GG genotype of the rs1805087 gene was found only in patients with DR, and was characterized by the maximum content of ET-1. In the carriers of AS polymorphism of the rs1801131 gene, an 8-fold increase in ET-1 was found during the development of DR.&#x0D; The minor GG genotype of the rs1805087 gene was found only in patients with DR, and was characterized by the maximum content of ET-1. In the carriers of AS polymorphism of the rs1801131 gene, an 8-fold increase in ET-1 was found during the development of DR. The minor SS genotype of this gene was twice as common in patients, and the ET-1 content increased 5 times with the development of DR.&#x0D; The presence of ST polymorphism of the rs1801133 gene and the AA genotype of rs1801131 are probably factors that prevent the development of DR. The ST gene rs1801133 polymorphism was accompanied by the lowest ET-1 content. The AA genotype of the rs1801131 gene was 1.3 times less frequent, the ET-1 content in these individuals was the lowest and practically did not change during the development of DR.

Prevalence of MTHFR Gene (C677T and A1298C) Polymorphism in the Syrian Coastal Area

Prevalence of MTHFR Gene (C677T and A1298C) Polymorphism in the Syrian Coastal Area