Association of Methylenetetrahydrofolate Reductase (MTHFR-677 and MTHFR-1298) Genetic Polymorphisms with Occlusive Artery Disease and Deep Venous Thrombosis in Macedonians (original) (raw)
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Balkan Medical Journal, 2013
Background: Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have recently raised the interest as a possible thrombophilic factors. Aims: We aimed to assess the frequency of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in idiopathic venous thromboembolism (VTE) in a Romanian population and the associated risk of VTE. Study Design: We performed a case-control transversal study including 90 patients diagnosed with VTE and 75 sex-and age-matched controls. Methods: MTHFR C677T and A1298C polymorphisms were detected using PCR-RFLP method. Results: The homozygous MTHFR 677TT genotype, present in 18.8% of patients with VTE versus 6.6% of controls, was significantly associated with VTE (p= 0.021, OR= 3.26, 95%CI (1.141-9.313)). The heterozygous MTHFR A1298C genotype, presenting the highest prevalence in the VTE group (34.4%) as well as in controls (37.3%), was not associated with VTE (p=0.7). No associations were found for heterozygous MTHFR C677T (with a frequency of 32.2% in VTE and 37.3% in controls, p=0.492), respective homozygous MTHFR A1298C genotype (with a frequency of 1.1% in VTE and 2.6% in controls, p=0.456). Conclusion: Among MTHFR polymorphisms, only homozygosity for MTHFR 677TT may be considered a risk factor for VTE; the MTHFR A1298C polymorphism is not significantly associated with an increased risk of VTE.
Iranian Red Crescent Medical Journal, 2014
Background: Recurrent pregnancy loss (RPL) is a serious problem for pregnancy. There is evidence that vascular complications play a principal role in RPL. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Polymorphisms (C677T, A1298C) of MTHFR gene are associated with decreased MTHFR activity. Objectives: The aim of this study was to determine the association between MTHFR polymorphisms (C677T and A1298C) and recurrent pregnancy loss (RPL) in Iranian women. Materials and Methods: In this case-control study, blood samples were obtained from patients who had three or more consecutive pregnancy losses before the 22 nd week of pregnancy (n = 204). The control group consisted of 116 age-matched women with at least one alive child and without any history of pregnancy loss or other gestational complications (n = 116). Following DNA extraction, samples were tested for MTHFR C677T and A1298C polymorphisms using the reverse hybridization method. Results: The prevalence of 677TT mutation was 8.8% (18/204) in the patient group and 8.6% (10/116) in the control group (P = 0.434). The prevalence of 1298CC mutation was 12.3 % (25/204) in the patient group and 8% (9/116) in the control group (P = 0.155). Investigation of the distributions of various genotypes of MTHFR C677T and A1298C did not indicate a significant difference between patients with RPL and healthy control subjects. Conclusions: The results suggest that MTHFR mutations might not be associated with RPL in the examined population.
MTHFR C677T Polymorphism in Turkish Women with Polycystic Ovary Syndrome
The Turkish Journal of Endocrinology and Metabolism
Objective: Polycystic ovary syndrome (PCOS) is one of the most common endocrine-reproductive-metabolic disorders of women at reproductive age, affecting 5-15% of the women worldwide. Although the pathogenesis of PCOS is not well defined, it is associated with an increased risk of premature coronary artery disease (CAD). Hyperhomocysteinemia (HHcy) is associated with hyperlipidemia and is an independent risk factor for CAD. The most common cause of HHcy is related to the deficiency of methylenetetrahydrofolate reductase (MTHFR). This study aimed to investigate the relationship between different genotypes of MTHFR C677T and the risk of PCOS. Material and Methods: Two hundred twenty voluntary premenopausal women (110 healthy controls and 110 PCOS patients) were included in the study. All the volunteers underwent a physical examination along with biochemical hormonal evaluation and genetic analysis. Results: The genotyping analyses and genetic model of inheritance analyses revealed that the frequencies of CC, CT, and TT genotypes in the control and PCOS group to be 51.8%, 45.5%, and 2.7% and 51.8%, 48.2%, and 0%, respectively. The frequency of C and T alleles in the control and PCOS group was determined to be 74% (C: 0.74/155) and 26% (T: 0.26/53), and 75% (C: 0.75/167) and 25% (T: 0.25/53), respectively. The "T" additive, "T" dominant, and "C" recessive models it found that the CT vs. CC (OR:1.06 Cl:0.62-1.83), CC vs. TC+TT (OR: 0.99 Cl: 0.58-1.72), and TC+TT vs. CC (OR: 0.99 Cl: 0.58-1.70), respectively, did not show an increase in the PCOS risk. Conclusion: Our findings indicated that the different genotypes of MTHFR C677T were not associated with the risk of PCOS in Turkish women from Central Anatolia.
Biomedical Reports, 2018
Several studies have investigated the link between two different polymorphisms (C677T and A1298T) of the gene encoding methylenetetrahydrofolate reductase (MTHFR) and the risk of recurrent pregnancy loss (RPL); however, the results remain controversial. This study aimed to provide greater insight into this debated topic. In the current study, two groups of pregnant women (group A: RPL women; group B: non-RPL women), each of which were subdivided further into two subgroups based on their gestational age, were screened for C677T and A1298T variants of the MTHFR gene. The resulting data were analyzed using receiver operating characteristic (ROC) curve and Z test methods to compare the two groups. These ROC curve and Z test analyses indicated that there were no differences between the groups regarding C677T and A1298T expression. RPL is primarily caused by mutations in prothrombin or factor V Leiden genes. However, a low percentage of RPL cannot be attributed to these mutations. In the last five years, research has focused on the MTHFR gene, the two major variants of which (C677T and A1298T) have been associated with an increased risk of cardiovascular diseases (thrombotic events) in homozygous individuals. In addition, these mutations may be related to an increased rate of neural tube defects in fetuses. While a link between MTHFR mutation and RPL may be expected based on previous findings, the present study indicated the absence of an association between the polymorphisms of the MTHFR gene and RPL risk.
Gynecological Endocrinology, 2014
Background: Methylenetetrahydrofolate reductase (MTHFR) has a major impact on the regulation of the folic acid pathway due to conversion of 5,10-methylenetetrahydrofolate (methylene-THF) to 5-methyl-THF. Two common polymorphisms (677C>T and 1298A>C) in the gene coding for MTHFR have been shown to reduce MTHFR enzyme activity and were associated with the susceptibility to different disorders, including vascular disease, neural tube defects and lymphoid malignancies. Studies on the role of these polymorphisms in the susceptibility to acute lymphoblastic leukemia (ALL) led to discrepant results. Methods: We retrospectively evaluated the association of the MTHFR 677C>T and 1298A>C polymorphisms with pediatric ALL by genotyping a study sample of 443 ALL patients consecutively enrolled onto the German multicenter trial ALL-BFM 2000 and 379 healthy controls. We calculated odds ratios of MTHFR genotypes based on the MTHFR 677C>T and 1298A>C polymorphisms to examine if one or both of these polymorphisms are associated with pediatric ALL. Results: No significant associations between specific MTHFR variants or combinations of variants and risk of ALL were observed neither in the total patient group nor in analyses stratified by gender, age at diagnosis, DNA index, immunophenotype, or TEL/AML1 rearrangement. Conclusion: Our findings suggest that the MTHFR 677C>T and 1298A>C gene variants do not have a major influence on the susceptibility to pediatric ALL in the German population.
Iranian journal of pediatric hematology and oncology, 2017
Two polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, were hypothesized to decrease the risk of acute lymphoblastic leukemia (ALL). Studies examining the associations between these two polymorphisms and ALL susceptibility drew inconsistent results. To obtain a reliable conclusion in a Chinese population, we carried out a meta-analysis. In total, 11 studies on C677T polymorphism (1597 cases and 2295 controls) and 10 studies on A1298C polymorphism (1553 cases and 2224 controls) were included in the meta-analysis. We found a significant association between the 677T variant and reduced ALL risk in Chinese children (Dominant model: odds ratio [OR FE ] = 0.73, 95% confidence interval [CI]: 0.63-0.86, p < 0.01). Heterogeneity between the studies in the children subgroup was weak and vanished after excluding one study deviating from HWE in the control group (p > 0.1). In the adult subgroup, there was no significant association between the C677T variant and ALL risk (Dominant model: OR RE = 0.88, 95% CI: 0.45-1.72, p = 0.72). Significant heterogeneity was found in the adult subgroup in all the genetic model tests (p < 0.1). The A1298C polymorphism had an effect on ALL risk neither in adults (Dominant model: OR FE = 0.95, 95% CI: 0.71-1.27, p = 0.72) nor in children (Dominant model: OR FE = 1.02, 95% CI: 0.87-1.21, p = 0.77). No significant heterogeneity between studies on A1298C polymorphism was found in the meta-analysis (p > 0.1). The results showed that there was a protective effect of the MTHFR C677T variant on ALL risk in Chinese children.
Labmedicine, 2008
Venous thrombosis, including deep-vein thrombosis and pulmonary embolism, is a common cause of morbidity and mortality, particularly in older people. 1 Venous thrombosis (VT) is multifactorial, and its exact pathogenesis has not been fully elucidated. Most cases of venous thrombosis arise due to prolonged immobilization, major surgery, trauma, or cancer, but genetic or acquired hemostatic abnormalities, including elevated plasma homocysteine (Hcy) levels, have also been implicated. 2 Elevated concentrations of total homocysteine have been associated with an increased risk of arterial and venous thrombosis. 3-5 A point mutation, C to T substitution at the nucleotide 677, in the coding sequence of the gene for methylenetetrahydrofolate reductase (MTHFR) is the most common enzyme defect associated with moderately-raised homocysteine concentrations, particularly in the presence of a suboptimal folate intake. 6 Genetic analyses studying the prevalence of the 677 C to T mutation in the MTHFR gene have recently shown divergent results in patients with venous thrombotic disease from different geographic regions. Several studies in patients with venous thrombosis failed to demonstrate an association between MTHFR C677T polymorphism and increased risk of venous thrombotic disease, 7,8,19-22 whereas other studies have reported a positive association. 9,17,18 In view of this controversy, our study was conducted with the purpose of evaluating the potential association of the C677T mutation of the MTHFR gene with venous thrombosis in adult patients. Materials and Methods Patients and Controls The present case control study included 200 patients with VT and 100 healthy controls. Cases and controls were recruited simultaneously from the same geographic area. Diagnosis of VT was made by ultrasonography, radioisotope venography, and magnetic resonance imaging angiography. 22 Patients who had an acquired disorder that predisposed them to VT were excluded from the study. These acquired disorders included malignancy, myeloproliferative disorder, nephrotic syndrome, liver disease, antiphospholipid syndrome, or pregnancy. The inclusion criteria for controls were: routine biochemical values within the normal range, nonsmokers, and no history of metabolic, renal, malignant, or vascular pathology. The exclusion criteria also included history of thrombosis and supplementary intake of vitamins. Homocysteine assay was carried out by ELISA method using Axis Homocysteine kit (Axis-Shield, Dundee, Scotland). Genetic Analysis Genomic DNA was extracted from the peripheral blood leukocytes by a previously described method. 10 The C677T mutation in the MTHFR gene was analyzed by PCR-RFLP using forward primer 5'-TGAAGGAGAAGGTGTCTGCGGGA-3' and reverse primer 5'-AGGACGGTGCGGTGAGAGTG-3'. PCR was carried out in a total volume of 40 µL containing 0.5 µmol/L of each primer, 200 µmol/L of all 4 dNTPs, 10 mmol/L Tris-HCl (pH 8.9), 2.2 mmol/L MgCl 2 , 10% glycerol, 50 mmol/L KCl, 1.
Clinical and Applied Thrombosis-Hemostasis, 2018
Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T)] is a well-recognized genetic risk factor for venous thrombosis; however, its association with arterial thrombosis is still under debate. Herein, we evaluated the prevalence of MTHFR C677T polymorphism in Georgian patients in comparison with healthy individuals and its association with arterial thrombosis. We enrolled 214 participants: 101 with arterial thrombosis (71.3% males; mean age: 66.3 + 12.1 years) and 113 controls (67.3% males; mean age: 56.6 + 11.3 years). Genomic DNA was extracted from dry blood spot on Whatman filter paper. Polymerase chain reaction was performed to determine MTHFR C677T polymorphism. Frequency of C677T allele polymorphism in controls was 21.2%, which corresponded to heterozygous and homozygous stage frequencies of 35.4% and 3.5%, respectively. In patient group, an allelic frequency of 33.2% was found, which corresponded to the presence of 48.5% of heterozygous and 8.9% of homozygous individuals. Comparing the frequency of mutated alleles between the 2 groups, a significantly high frequency of mutated alleles was found in patient group (P < .05). In conclusion, high frequency of MTHFR C677T polymorphism found in arterial thrombosis patient group suggests that this polymorphism might increase the risk of arterial thrombosis in Georgian patients.