C677T Mutation In Methylenetetrahydrofolate Reductase Gene Research Articles

Relationship between methylenetetrahydrofolate reductase C677T gene polymorphism and neutrophil gelatinase-associated lipocalin in early renal injury in H-type hypertension

ObjectiveTo analyse the relationship between the polymorphisms of the H-type hypertensive methylenetetrahydrofolate reductase (MTHFR) C677T gene and neutrophil gelatinase-associated lipocalin (NGAL) in early kidney injury.MethodA total of 279 hospitalised patients with hypertension were selected and grouped according to their homocysteine (Hcy) level. If their blood Hcy level was ≥ 10 µmol/L they were assigned to the H-type hypertensive group, and if it was < 10 µmol/L they were assigned to the non-H-type hypertensive group. Blood lipid indexes, renal function indexes and blood glucose indexes were collected, and the differences between the two groups were compared. Furthermore, MTHFR C677T genotype distribution and allele frequency and Hcy level of MTHFR C677T genotype were compared, and logistic multiple regression analysis was conducted for the correlation of different genotypes of MTHFR C677T and the early kidney injury marker NGAL.ResultsIn the non-H-type hypertensive group, the levels of Hcy and NGAL, cystatin, blood urea nitrogen, serum creatinine, uric acid, serum β2-microglobulin and urinary microalbumin-to-creatinine ratio increased significantly, and the glomerular filtration rate level decreased significantly, when compared with the H-type hypertensive group, with statistical differences (p < 0.05). The H-type hypertensive group and the non-H-type hypertensive group had significant differences in the CC, CT and TT genotypes and allele frequencies at the MTHFR C677T locus. The MTHFR C677T gene mutation rate of the H-type hypertensive group was significantly higher than that of the non-H-type hypertensive group. The H-type hypertensive group had higher levels of the TT genotype and CT genotype Hcy. There was a statistical difference (p < 0.05).ConclusionMethylenetetrahydrofolate reductase C677T polymorphism is correlated with the Hcy level, and its gene polymorphism will affect the Hcy level. Methylenetetrahydrofolate reductase C677T polymorphism has an interactive effect with NGAL. Screening NGAL and reducing Hcy levels are valuable methods for the prevention and treatment of early renal injury in patients with H-type hypertension and help improve the prognosis of patients and their quality of life.

A Curious Case of Acute STEMI in a Young Patient; Things are Not Always What They Seem

BACKGROUND: Acute myocardial infarction (MI) is a rare occurrence in patients under 40 years of age without positive family history for coronary artery disease (CAD). Genetic conditions as inherited thrombophilia can lead to a hypercoagulable state, resulting in thromboembolic events and arterial thrombosis. CASE SUMMARY: We present a case of a 35-year-old male patient who presented to the emergency room with an inferior MI after a strenuous cycling exercise. An urgent coronary angiography showed thrombotic formations in the right coronary artery without atherosclerotic plaques. Plain old balloon angioplasty and thrombus aspiration were performed, which was followed by GP IIb/IIIa inhibitor infusion and unfractionated heparin for 24 h. From past medical history, the patient had COVID-19 like symptoms 20 days before the event and had his first dose of anti- COVID vaccine 2 weeks prior. After additional testing, molecular genetic analysis results revealed the patient to be heterozygous for factor V Leiden (FVL) and homozygous for methylenetetrahydrofolate reductase C677T gene mutation. The patient was discharged on direct oral anticoagulant and antiplatelet therapy. After 1-year follow-up, he had no symptoms or recurrent cardiovascular events. CONCLUSION: Inherited thrombophilia is а significant risk factor for CAD and performing genetic testing in younger patients with a cardiovascular event and plays an important role for adequate treatment and prophylaxis from recurrent complications. The use of oral anticoagulation for prophylaxis is shown to be effective in these patients. However, further studies are needed to prove their exact role and duration of treatment.

Case Report: Homozygous C677T MTHFR Gene Mutation in Male with Hypogonadism

We report a 44-year-old male, who was diagnosed with hypogonadotropic hypogonadism after complaining of erectile dysfunction, depression, and fatigue. He was started on testosterone replacement therapy. He persistently complained of fatigue despite increasing the dose of testosterone over two years and having therapeutic testosterone levels. He was found to have homozygous C677T methylenetetrahydrofolate reductase (MTHFR) gene mutation. After treatment with folate and B12, his symptoms resolve completely. MTHFR is a key enzyme in the folate pathway, and it plays an essential role in homocysteine metabolism. Homozygous C677T individuals have decreased activity of MTHFR enzyme with increased homocysteine levels, which is associated with increased risk of thrombosis. An association has been reported between C677T variant and male infertility. Patients identified to have hyperhomocysteinemia should be treated with B-complex vitamin supplements. Our case emphasizes other possible etiologies for fatigue and erectile dysfunction in a male with hypogonadism on testosterone therapy. Also, it shows possible association between MTHFR gene mutation and male hypogonadism.

Methylene tetrahydrofolate reductase gene mutation in sickle cell anaemia patients in Lagos, Nigeria.

IntroductionThe significant causes of mortality among individuals with sickle cell anaemia (SCA) such as acute chest syndrome and cerebrovascular disease are related to vascular occlusion. Polymorphisms of the methylene tetrahydrofolate reductase (MTHFR) gene in persons with sickle cell anaemia have been suggested as a potential risk for vaso-occlusive events, with the C677T and A1298C polymorphisms being the commonest. This study therefore aimed to establish the pattern of MTHFR C677T and A1298C gene mutations among adults with HbSS phenotype attending the Haematology Clinic in Lagos State University Teaching Hospital Lagos, Nigeria.MethodsA cross-sectional study was done among SCA patients attending the Haematology Clinic of the Lagos State University Teaching Hospital (LASUTH), using age and sex matched HbAA controls. DNA extraction and gene analysis were done. The selective amplification of a particular segment of the DNA by polymerase chain reaction (PCR) was done and subsequent digestion of the amplified MTHFR gene into its various fragments.ResultsThe overall prevalence of the C677T mutation among participants was 19.3% (37 of 192), while the prevalence of A1298C was 15% (29 of 192).ConclusionThe prevalence of MTHFR C677T was higher than A1298C mutations among sickle cell anaemia subjects.

Сочетанная тромбофилия по данным гематологического консультирования

Введение. Диагностическая значимость гомозиготной мутации генов факторов свертывания крови FV Leiden и FII, а также их гетерозиготного полиморфизма в сочетании с маркерами первичного антифосфолипидного синдрома как предикторов тромбоза остается неоднозначной. Цель исследования: представить клинические случаи сочетанных тромбофилий, выявленных в процессе амбулаторного гематологического консультирования. Материалы и методы. В базе данных приема гематолога с января 2012 г. по апрель 2017 г. выявлен 891 пациент (837 женщин и 54 мужчины), которым было проведено обследование и консультирование на предмет тромбофилии и/или наличия активных факторов тромбогенного риска. Результаты. Сочетанная тромбофилия выявлена у 7 (0,8%) из 891 обследованного или у 7 (2,8%) из 246 пациентов с факторами тромбогенного риска. В 4 случаях у 2 мужчин (44 и 28 лет) и у 2 женщин (29 и 33 лет) диагноз установлен в связи с тяжелой и/или рецидивирующей венозной и артериальной тромбоэмболией и у 3 женщин (27, 36 и 39 лет) в связи с синдромом потери плода. Заключение. Анализ наблюдений подтверждает целесообразность поиска сочетанной тромбофилии в случае рецидивирующего тромбоза для выбора оптимальной антикоагулянтной терапии. Introduction. The diagnostic signifi cance of homozygous mutation of FV Leiden and FII clotting factor genes, as well as their heterozygous polymorphism in combination with the markers of the primary antiphospholipid syndrome as predictors of thrombosis remains ambiguous. Aim: to present clinical cases of combined thrombophilia revealed during outpatient hematology counseling. Materials and methods. In hematologist database from January 2012 to April 2017 we found 891 patients (837 women and 54 men) who were examined and consulted for thrombophilia and/or presence of active factors of thrombogenic risk. Results. Combined thrombophilia was identifi ed in 7 (0.8%) of 891 patients or in 7 (2.8%) of 246 patients with thrombogenic risk factors. In 4 cases — 2 men (44 and 28 years) and 2 women (29 and 33 years old) had a diagnosis due to severe and/or recurrent venous and arterial thromboembolism and 3 women (27, 36 and 39 years) had a diagnosis due to fetal loss syndrome. Conclusion. The observations confi rm the practicability of researching for combined thrombophilia in case of recurrent thrombosis for the choice of optimal anticoagulant therapy.

Glanzmann Thrombasthenia in a Newborn with Heterozygous Factor V Leiden and Heterozygous MTHFR C677T Gene Mutations

Glanzmann thrombasthenia is a rare congenital platelet dysfunction. A 2-day-old male neonate delivered at 35 weeks' gestation was referred with extensive bruising and jaundice. His elder sibling had Glanzmann thrombasthenia, and his mother had thrombophilic risk factors. Flow cytometric analysis revealed absent CD41/CD61. A molecular thrombophilia panel revealed the presence of heterozygous factor V Leiden G1691A and methylenetetrahydrofolate reductase C677T gene mutations. General precautions to avoid injuries and spontaneous bleeding were advised. Life-threatening bleeding may not be the first finding in cases of thrombasthenia accompanied by thrombophilic risk factors.

Homocysteinemia in relation to anemia in hypothyroid patients

Background Anemia and hypothyroidism are both common diseases in the community. Homocysteine (HCY) levels are increased in patients with hypothyroidism and methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common genetic cause of hyperhomocysteinemia. The aim of the present study was to evaluate the level of serum HCY in patients with hypothyroidism and to study the relation of associated anemia with the serum level of HCY and MTHFR gene in patients with hypothyroidism. Patients and methods The study was conducted on 60 adult women attending the Endocrinology Outpatient Clinic of Al-Zahraa Hospital between September 2014 and June 2015 for proper diagnosis and management. Individuals of the study were divided into two main groups: group I (GI) with 30 hypothyroid patients, where 13 of them were postsurgical cases, and group II (GII) with 30 euthyroid individuals as a control group. Diagnosis was based on thyroid-stimulating hormone level reference values. Patients in GI were further classified into two subgroups: mild hypothyroid (subgroup I) and overt hypothyroid (subgroup II). Patient and control groups also were classified into anemic and nonanemic subgroups according to hemoglobin levels. The selected hypothyroid patients were women under thyroid hormone replacement therapy. Blood sample was obtained for proper investigations. Complete blood count, routine blood chemistry, serum iron level, thyroid function tests, vitamin B12 level, serum homocysteine (HCY), and MTHFR were performed. We performed a pilot study on MTHFR gene polymorphism. The C677T MTHFR gene mutation was detected in three of 10 patients and in two of 10 controls. No evidence of TT MTHFR gene mutation was observed in both patient and control groups. IBM SPSS statistics (version 23.0, USA, 2015) was used for data analysis. Results revealed the presence of anemia according to hemoglobin level (&lt;12 g/dl). In patients group (GI), 50% (15/30) as compared with 13.3% (4/30) in the control group (GII) had anemia. Serum iron level in patients group (GI) was deficient in 40% (11/30), whereas deficient in 16.7% (5/30) in control group (GII). Vitamin B12 deficiency was found to be 44% (11/25) in patients group (GI), whereas in the control group (GII) was 6.7% (2/30). Analysis by Wilcoxon's rank sum test, homocysteine (HCY) serum level showed a highly significant increase among patients (GI) as compared with control (GII). Ranked Spearman's correlation test for the patients (GI) and control (GII) showed a significant negative correlation between homocysteine (HCY) and MTHFR serum levels, whereas the correlation with red cell indices parameters was insignificant. Serum iron and B12 levels were significantly correlated in patient group (GI). Pearson χ 2 tests were done between both patients and control groups for the presence of anemia, iron deficiency, and elevated serum homocysteine (HCY) level and all revealed statistically significant results. Conclusion There is no significant correlation between homocysteinemia and anemia. However, the strong association between anemia and hypothyroidism is attributed mainly owing to combined iron and vitamin B12 deficiencies. This might explain the decreased response to treatment among the selected hypothyroid patients.

The clinical effects of methylenetetrahydrofolate reductase C677T gene mutation on mild vascular cognitive impairment in patients with cerebral infarction

Objective To study the clinical effects of methylenetetrahydrofolate reductase(MTHFR)C677T gene mutation on mild vascular cognitive impairment(VCI)in patients with cerebral infarction. Methods The prospective study was conducted in 180 patients with atherosclerotic acute cerebral infarction hospitalized from June 2015 to May 2016.180 patients were divided into normal homocysteine(Hcy)group(Hcy 5.46~16.20 μmol / L, n=130)and high Hcy group(Hcy>16.20 μmol / L, n=50). MTHFR C677T genotypes were detected by polymerase chain reaction-restriction endonuclease fragment length polymorphism.The VCI state and risk factors for VCI were analyzed with Montreal Cognitive Assessment scale(MoCA)and Mini Mental State Examination(MMSE)score in patients with acute cerebral infarction on admission and 14 days, 30 days and 90 days after admission. Results MMSE and MoCA scores at 14 days, 30 days, 90 days after admission were lower in high Hcy group than in normal Hcy group(P<0.05 or P<0.01). MMSE and MoCA scores were lower in T/T genotype than in C/C genotype(P<0.05)at 14 day after admission, and lower in C/T genotype than in C/C genotype at 30 day and 90 day follow-up(P<0.05 or P<0.01). Logistic regression analysis showed that Hcy may be independent risk factors for mild VCI(OR=1.274, 95%CI: 1.027~1.264, P=0.018). Conclusions MTHFR C677T gene mutations may cause hyper-homocysteinemia, and promote the emergence of VCI in patients with cerebral infarction.MTHFR C677T gene mutations may be a genetic susceptibility factor for VCI. Key words: Brain infarction; Methylenetetrahydrofolate reductase; Cognition disorders

Thrombophilic Status of Extracted Fetal Tissues of Spontaneously Aborted Embroys

Objective : The reports about Factor V (FV) Leiden, Factor II (FII) G20210A and Methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations of parents and fetal viability are frequently encountered in the literature, despite the fetal side of thrombophilia is scant. To clarify the three common thrombophilic gene mutations of the spontaneously aborted embryos, an accurate algorithm was followed to extract the fetal tissues and then the mutations were searched. Material and Methods : 70 spontaneous abortion materials were included to the study and all were karyotyped. Cytogenetically abnormals were excluded from the study. To extract the fetal tissues, amplifications of sex determination region of chromosome-Y (SRY) gene and genotypings were performed, respectively. Extracted fetal tissues of spontaneous aborted embroys and parents were screened for the thrombophilic gene mutations via electronic microarray. Results: After excluding chromosomally abnormal and maternally contaminated ones totally ten fetal tissues were screened for the FII G20210A, FV Leiden and MTHFR C677T gene mutations, and two carry F II G20210A and F Leiden heterozygote mutations, and six carry heterozygote forms of MTHFR C677T. Conclusion : The present study performed on the limited number of abortion materials, has a value for distinguishing the fetal tissues before analyzing the three common mutation of thrombophilic genes which make the results are very substantial.

Factor V Leiden, factor V Cambridge, factor II GA20210, and methylenetetrahydrofolate reductase in cerebral venous and sinus thrombosis: A case-control study.

Background:Factor V G1691A (FV Leiden), FII GA20210, and methylenetetrahydrofolate reductase (MTHFR) C677T mutations are the most common genetic risk factors for thromboembolism in the Western countries. However, there is rare data in Iran about cerebral venous and sinus thrombosis (CVST) patients. The aim of this study was to evaluate the frequency of common genetic thrombophilic factors in CVST patients.Materials and Methods:Forty consequently CVST patients from two University Hospital in Isfahan University of Medical Sciences aged more than 15 years from January 2009 to January 2011 were recruited. In parallel, 51 healthy subjects with the same age and race from similar population selected as controls. FV Leiden, FII GA20210, MTHFR C677T, and FV Cambridge gene mutations by polymerase chain reaction technique were evaluated in case and control groups.Results:FV Leiden, FII GA20210, and FV Cambridge gene mutations had very low prevalence in both case (5%, 2%, 0%) and control (2.5%, 0%, 0%) and were not found any significant difference between groups. MTHFR C677T mutations was in 22 (55%) of patients in case group and 18 (35.5%) of control group (P = 0.09).Conclusion:This study showed that the prevalence of FV Leiden, FII GA20210, and FV Cambridge were low. Laboratory investigations of these mutations as a routine test for all patients with CVST may not be cost benefit.

Association between the methylenetetrahydrofolate reductase gene C677T polymorphism and sudden sensorineural hearing loss: a meta-analysis.

A variety of epidemiological studies have evaluated the association between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and sudden sensorineural hearing loss (SSNHL), but the results were inconsistent. The aim of this meta-analysis was to clarify more accurately the association of this polymorphism with SSNHL. A systematic literature search of the associated studies up to May 1, 2014, was conducted using the following electronic databases: PubMed, Embase, Medline, and the China National Knowledge Infrastructure. Statistical analyses were performed by STATA12.0 software, with odds ratios (ORs) and their 95 % confidence intervals (CIs). Six eligible studies including covering 1,271 objects were identified. A pooled analysis of these studies showed no significant association between C677T polymorphism and risk of SSNHL: T vs. C (OR = 1.334, POR = 0.105); TT vs. CC (OR = 1.580, POR = 0.231); CT vs. CC (OR = 1.500, POR = 0.123); TT vs. CC + CT (OR = 1.326, POR = 0.293); and TT + CT vs. CC (OR = 1.540, POR = 0.102). But in subgroup analysis, a significant association was found in European populations (T vs. C, OR = 1.542, 95 % CI 1.008-2.359, P = 0.046; TT vs. CT + CC, OR = 1.856, 95 % CI 1.245-2.767, P = 0.002). There was no significant association in any model in the Asian populations. The present meta-analysis suggests that MTHFR gene C677T polymorphism is significantly associated with increased risk of SSNHL disease in European populations, but no statistically significant association was found between the MTHFR C677T gene mutation and SSNHL in Asian. Further large and well-designed studies are needed to confirm this association.

Association of MTHFR gene C677T mutation with recurrent aphthous stomatitis and number of oral ulcers

Recurrent aphthous stomatitis (RAS) is a common ulcerative disease of the oral mucosa. Methylenetetrahydrofolate reductase (MTHFR) gene variants are associated with thrombophilia and vasculopathy that may result in oral ulceration. Oral ulcers are also the most common feature of Behcet's disease (BD). Association of MTHFR gene C677T mutation with BD has been reported in different populations. The aim of the present study was to investigate the possible association between MTHFR gene C677T mutation and RAS and evaluate if there was an association with clinical features in a relatively large cohort of Turkish patients. The study included 188 patients affected by RAS and 200 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MTHFR gene C677T mutation. The genotype and allele frequencies of C677T mutation showed statistically significant differences between RAS patients and controls (p = 0.002 and p = 0.0004, respectively). After stratifying RAS patients according to clinical characteristics of oral ulcers, a significant association was observed between C677T mutation and number of oral ulcers of RAS patients (p = 0.006). As a result, a high association between MTHFR gene C677T mutation and RAS was observed in the present study. Also number of oral ulcers was found to be associated with MTHFR C677T mutation in RAS patients. If our observation can be substantiated with further studies, evaluation for MTHFR mutations and perhaps folate supplementation may become necessary in selected patients.

Coexistence of Neurofibromatosis Type-1 and MTHFR C677T Gene Mutation in a Young Stroke Patient: A Case Report

In neurofibromatosis type-1 (NF1), cerebrovascular disorders are rarely encountered although vasculopathy is a well-known complication. Several mutations seen in methylenetetrahydrofolate reductase (MTHFR) give rise to the formation of hyperhomocysteinemia and homocystinuria, a considerable risk factor for cardiovascular and cerebrovascular disorders, by leading to enzymatic inactivation. In the paper, a 31-year-old young stroke female patient with the coexistence of neurofibromatosis and MTHFR C677T gene mutation was presented.

Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain

Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM). There is a wide variation in the prevalence of MTHFR polymorphisms and homocysteine (Hcy) plasma levels among populations around the world. The present study was undertaken to investigate the possible association between hyperhomocysteinemia and its causative genetic or acquired factors and RM in Catalonia, a Mediterranean region in Spain. Sixty consecutive patients with ≥ 3 unexplained RM and 30 healthy control women having at least one child but no previous miscarriage were included. Plasma Hcy levels, MTHFR gene mutation, red blood cell (RBC) folate and vitamin B12 serum levels were measured in all subjects. No significant differences were observed neither in plasma Hcy levels, RBC folate and vitamin B12 serum levels nor in the prevalence of homozygous and heterozygous MTHFR gene mutation between the two groups studied. In the present study RM is not associated with hyperhomocysteinemia, and/or the MTHFR gene mutation.

MTHFR gene C677T mutation and ACE gene I/D polymorphism in Turkish patients with osteoarthritis.

Osteoarthritis is a degenerative joint disorder resulting in destruction of articular cartilage, osteophyte formation, and subchondral bone sclerosis. In recent years, numerous genetic factors have been identified and implicated in osteoarthritis. The aim of the current study was to examine the influence of methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) variations on the risk of osteoarthritis.Genomic DNA is obtained from 421 persons (221 patients with osteoarthritis and 200 healthy controls). ACE gene I/D polymorphism genotypes were determined using polymerase chain reaction using I and D allele-specific primers. The MTHFR C677T mutation was analyzed by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) methods. We found significant difference between the groups with respect to both ACE and MTHFR genotype distributions (p < 0.001, p < 0.001 respectively). Our study suggests that ACE gene DD genotype and MTHFR gene CC genotype could be used as genetic markers in osteoarthritis in Turkish study populations.

PP-206: HYPERHOMOCYSTEINEMIA AND ACUTE ANTERIOR MYOCARDIAL INFARCTION IN A YOUNG WOMAN

Objective: Hyperhomocysteinemia arising from impaired methionine metabolism. It is regarded as independent risk factor for ischemic vascular diseases and thrombosis. Homocysteine may impair vascular endothelial cell function. it may also induce oxidation of low-density lipoproteins. its deleterious effect on vascular endothelium, might be associated with an increase in coronary thrombosis during acute myocardial infarction. We report a 19 year old woman with an acute myocardial infarction associated with hyperhomocysteinemia. Methods: A 19-year old woman was admitted to our hospital because of a six hour history of typical chest pain and hospitalized with diagnosis of acute anterior myocardial infarction. His past medical was unremarkable. She was not taking oral contraceptives or any other medication. Family history showed that the patient’s mother had had a deep vein thrombosis and her father was healthy. Initial physical examination revealed blood pressure of 110/70 mmHg, respiratory rate of 27/min, and a pulse rate of 90/min. On cardiac auscultation, heart sounds were soft and 1/6 systolic murmur was heard in the mezocardiac area. The respiratory sounds on auscultation were normal. The electrocardiogram showed marked ST segment elevation in the anterior leads. The patient was submitted to catheterization laboratory for percutaneous coronary intervention. Coronary angiography showed normal right, left main, and left circumflex coronary arteries and total occlusion of the proximal left anterior descending coronary artery (LAD) (Figure 1a). The LAD was successfully revascularized with percutaneous balloon angioplasty (Figure 1b). Results: Coagulability testing showed elevaed homocysteine levels (50 mmol/l). Genetic testing for the methylenetetrahydrofolate reductase C677T gene mutation was positive. She was treated with heparin intravenously followed by warfarin.

Methylenetetrahydrofolate reductase C677T gene mutation as risk factor for sudden sensorineural hearing loss: association with plasma homocysteine, folate and cholesterol concentrations

Impaired cochlear perfusion appears to be the most important event in the development of sudden sensorineural hearing loss. Methylenetetrahydrofolate reductase gene mutations at nucleotide 677 cause reduced methylenetetrahydrofolate reductase enzyme activity, resulting in vascular impairment. Thirty-three patients and 68 control subjects underwent audiological and haematological investigation. No statistically significant association was found between sudden sensorineural hearing loss and the methylenetetrahydrofolate reductase C677T gene mutation. Mean homocysteine and cholesterol concentrations were significantly higher in patients than in controls. Mean folate levels were significantly lower in patients than in controls. Amongst patients with sudden sensorineural hearing loss, no significant differences in mean cholesterol, homocysteine or folate concentration were found, comparing patients with methylenetetrahydrofolate reductase C677T mutation genotypes with those without. No statistically significant association was found between the methylenetetrahydrofolate reductase C677T gene mutation and sudden sensorineural hearing loss. There was a statistically significant difference between the homocysteine, folate and cholesterol concentrations of sudden sensorineural hearing loss patients, compared with controls. However, there was no statistically significant difference in these levels, comparing patients with and without the methylenetetrahydrofolate reductase C677T mutation.

Portal vein thrombosis in Egyptian patients with liver cirrhosis: Role of methylenetetrahydrofolate reductase C677T gene mutation

The pathogenesis of non-malignant portal vein thrombosis (PVT) in cirrhotic patients is not clearly defined. This case-control study aimed to investigate the role of methylenetetrahydrofolate reductase (MTHFR) C677T gene mutation in the pathogenesis of PVT in Egyptian cirrhotic patients. Plasma homocysteine was measured and MTHFR C677T gene mutation was detected in 76 cirrhotic patients (21 with PVT, 55 without PVT) and 20 healthy controls. The frequency of CC genotype (wide type) in cirrhotic patients with PVT was lower than controls and cirrhotics without PVT. However, the frequency of TT genotype (homozygous mutation) was elevated in cirrhotic patients with PVT as compared to controls and those without PVT. Cirrhotic patients with PVT had significantly higher homocysteine than those without PVT. Cirrhotic patients with TT genotype are at a significant risk for PVT (odds ratio = 7.7, 95% confidence interval, 1.50-42.81) when compared with CC genotype. Moreover, subjects carrying TT genotype had a higher homocysteine than those carrying CC genotype. The TT genotype of MTHFR is associated with an increased risk of PVT in Egyptian cirrhotic patients. Hyperhomocysteinemia could be considered as a relatively new risk factor for PVT in cirrhotic patients and plasma homocysteine should be investigated particularly in patients with PVT of unexplained etiology. The important clinical implication is that the readily available therapy of folate, vitamin B6 and B12 supplementation may reduce homocysteine and prevent further thrombotic complications in cirrhotic patients carrying the TT genotype.

Plasma Homocysteine, MTHFR Gene Mutation, and Open-angle Glaucoma

Elevated plasma homocysteine has been associated with an increased risk of cardiovascular disease. The association between open-angle glaucoma and cardiovascular disease has recently stimulated interest in the role of homocysteine in the pathogenesis of glaucoma. Some studies report elevated plasma homocysteine in patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma (PXFG), but have not found this association consistently in other types of open-angle glaucoma. In this study, we have measured plasma homocysteine and C677T methylenetetrahydrofolate reductase (MTHFR) mutation, the commonest genetic cause of elevated plasma homocysteine, in patients with PXFG, primary open-angle glaucoma (POAG), and normal tension glaucoma (NTG). Prospective cross-sectional cohort study. Forty-eight patients with PXFG, 36 patients with POAG, 34 patients with NTG, and 42 controls without glaucoma. Fasting venous blood samples from each participant were analyzed for plasma homocysteine and the C677T MTHFR gene mutation. MAIN OUTCOME OF INTEREST: Mean plasma homocysteine levels, number of individuals with homocysteine above the reference range, and percentage of individuals with heterozygous or homozygous C677T MTHFR gene mutations. Mean plasma homocysteine was significantly higher in PXFG (11.77+/-4.18 micromol/L), POAG (11.21+/-2.84 micromol/L), and NTG (11.74+/-3.79 micromol/L) compared with control (9.82+/-1.75 micromol/L). Hyperhomocysteinemia was found in 27.1% of PXFG patients, 30.6% of POAG patients, and 29.4% of NTG patients. There was no significant difference in frequency of MTHFR C677T gene mutation between groups. Plasma homocysteine was elevated in PXFG, POAG, and NTG. Elevated plasma homocysteine seems to be associated with glaucoma in these patients.

Polymorphism of the methylenetetrahydrofolate reductase gene association with homocysteine and ischemic stroke in type 2 diabetes

Ischemic stroke is a frequent heterogeneous multifactorial disease. A number of genetic mutations and environmental factors have been implicated. A polymorphism in the gene for methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated with hyperhomocysteinemia a risk for atherosclerotic vascular diseases. A cross-sectional study was performed to determine the relationship between the gene polymorphism for MTHFR and ischemic stroke in type 2 diabetes mellitus. Of the 215 unrelated patients with type 2 diabetes mellitus recruited, 119 patients had ischemic stroke, Control group included 142 healthy subjects. The genotype of the subjects for the C677T polymorphism of MTHFR was analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by HinfI digestion. Plasma total homocysteine (Hcy) levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. The genotype distribution did not differ between the control subjects and type 2 diabetic patients (P > 0.05). Plasma homocysteine levels were markedly higher in diabetic patients with TT genotype than those with CC or CT genotype (P > 0.05). Ischemic stroke was more frequently observed in type 2 diabetic patients with the TT genotype than in those with the CT and CC genotype (odds ratio = 4.04, 95% CI = 1.95-8.34, P = 0.0036). Logistic regression analysis revealed that the C677T mutation of MTHFR gene was independently associated with ischemic stroke in type 2 diabetes. MTHFR C677T gene polymorphism associated with a predisposition to hyperhomocysteinemia could constitute a useful predictive marker for ischemic stroke in type 2 diabetic Chinese patients.