Methylenetetrahydrofolate Reductase A1298C Mutations Research Articles

Hydropneumothorax – Rare presentation of pulmonary embolism with methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia

Pulmonary embolism (PE) is a relatively common cardiovascular event with high early mortality rates. Many risk factors play a role in the causation of PE including acquired as well as inherited. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is one of the inherited etiologies for PE which cause hyperhomocysteinemia which can lead to PE. This in turn can result in secondary complications such as pneumothorax or hydropneumothorax, which are rare presentations of PE. Hereby, we present this unique case of a 17-year-old boy who presented with a hydropneumothorax which on further evaluation was found to be a complication of bilateral PE which was due to hyperhomocysteinemia with MTHFR A1298C mutation. Hence, we present this unique case with rare presentation as well as rare etiology for PE. This shows the significance for considering PE as one of the differentials in situations such as cavitations, pneumo or hydropneumothoraces, and hyperhomocysteinemias.

Effect of Genetic Factors on the Etiopathogenesis of Thrombosed Hemorrhoidal Disease.

The aim of this study is to investigate whether genetic factors known to increase thrombosis risk play a role in the etiopathogenesis of thrombosed hemorrhoidal disease. Methods: Genomic DNA from patients with thrombosed hemorrhoidal disease was analyzed for the presence of factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase C677T, and methylenetetrahydrofolate reductase A1298C mutations. Results: No significant differences were found in the allele frequencies of factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase C677T, and methylenetetrahydrofolate reductase A1298C mutations between patients with thrombosed hemorrhoidal disease and controls (p 0.05). Moreover, there were no significant differences in the genotype (heterozygous and homozygous mutations) of factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase C677T and A1298C mutations between patients with thrombosed hemorrhoidal disease and controls (p 0.05). Conclusions: Our findings indicate that mutations associated with venous thromboembolism do not play a role in the etiopathogenesis of thrombosed hemorrhoidal disease; however, several environmental, mechanical, and hemodynamic factors may contribute to the etiopathogenesis of hemorrhoidal disease.

Factor V Leiden G1691A, Prothrombin G20210A, and MTHFR C677T and A1298C Mutations in Patients With Sickle Cell Disease in Tunisia

Sickle cell disease is a genetic disorder characterized by a hypercoagulable state. Several complications in this hemoglobinopathy are increased by thrombosis. Factor V Leiden (FVL), prothrombin (PRT) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations are major inherited risk factors of thrombotic complications. In this study, our aim was to compare the frequencies of these mutations in sickle cell patients with healthy controls. The study population comprised 35 homozygous Hb S (HBB: c.20A>T) patients, 29 compound heterozygous patients [16 Hb S/β0-thalassemia (β0-thal), four Hb S/β+-thal, seven Hb S/Hb C (HBB: c.19G>A) and two Hb S/Hb O-Arab (HBB: c.364G>A)] and 100 healthy subjects. All patients and controls were subjected to laboratory investigations as well as mutation genotyping. Our findings showed a severe anemia with the lowest values of protein S (PS), protein C (PC) and antithrombin (AT) in the homozygous Hb S group compared to Hb S/Hb C and Hb S/β-thal subjects. No significant difference in FVL genotype between patients and controls was observed, whereas high frequencies of PRT G20210A, MTHFR C677T and MTHFR A1298C mutations in the Hb S patients and a significant association between the MTHFR C677T mutation and Hb S/β0-thal were found.

Thrombophilic Mutations Among Patients with Sickle Cell Disease.

Factor V-Leiden (FVL), Prothrombin (PRT) G20210A, and Methylene Tetrahydro Folate Reductase (MTHFR) C677T and A1298C mutations are major inherited risk factors of thrombotic complications. Our aim in this study was to investigate the prevalence of these mutations among Tunisian sickle cell patients. Study subjects comprised 64 patients and 100 healthy controls. FVL, PRT G20210A, and MTHFR genotypes were determined using a reverse dot blot based method. In the patient population studied, the prevalence of FV Leiden was not statistically different from controls while a significant prevalence of heterozygous PRT G20210A mutation among patients (10.93%) was found. An increased frequency of the MTHFR 677 C>T genotype was seen among patients as well as controls. The results showed no significant association between the MTHFR A1298C mutation and sickle cell disease (SCD). However, the prevalence of carrier among studied patients was 15.62% compared to 7% among healthy subjects. In conclusion, our data suggest a significant association between PRT G20210A and MTHFR C677T and sickle cell disease among Tunisian patients.

Association of Mycobacterium infections in patients with Mendelian susceptibility to mycobacterial disease with venous thromboembolism.

An association between a hypercoagulable state and Mendelian susceptibility to mycobacterial disease (MSMD) has been established in a few studies; resultant thrombosis is considered rare. In a case-control study, the prevalence of factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C mutations were investigated in mycobacterium-infected patients. The study comprised 30 patients with mycobacterial infections (invasive, disseminated and/or recurrent infections with Bacille Calmette-Guerin or non-tuberculosis mycobacteria and Mycobacterium Tuberculosis with positive results for acid-fast bacilli and tuberculin skin tests) and 30 normal healthy controls. Forty female (66.7%) and 20 male subjects (33.3%) aged from 3 to 70 years were recruited into this study. Genotyping of targeted genes was performed by RT-PCR and cytokine TNF-α concentrations were quantified using a commercially available ELISA kit. Significant associations between mycobacterial infection and TNF-α production after stimulating peripheral blood mononuclear cells with LPS alone and with IFN-γ plus LPS were identified. Moreover, genotyping analysis in the studied population revealed a significant association between MTHFR c.677C>T (OR, 3.28; 95% CI, 1.35-7.92; P < 0.05), MTHFR c.1298A>C (OR, 2.33; 95% CI, 1.10-4.93; P < 0.05) and mycobacterial infection in affected patients, indicating susceptibility to venous thromboembolism according to previous studies. Additionally, mycobacterium-infected patients had a significantly greater prevalence of MTHFR C677T and A1298C mutations than controls.

A Rare Case of Cerebral Sinovenous Thrombosis Associated withMTHFRA1298C and C677T Mutations

Neonatal cerebral sinovenous thrombosis (CSVT) is a rare disease with severe neu­ rological sequelae. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate cycle, and mutations in MTHFR are associated with vascular diseases. Here, we report the case of a newborn with MTHFR mutation­associated CSVT. Analysis of MTHFR in the patient detected heterozygous C677T (677CT) and A1298C (1298AC) mutations. Analysis of MTHFR in the patient's mother did not detect a C677T (677CC) mutation but detected a homozygous A1298C (1298CC) mutation. Our results suggest that the presence of heterozygous MTHFR C677T and A1298C mutations affect thrombophilic activity in the neonate, resulting in the development of refractory seizure and CSVT. Moreover, presence of the homozygous MTHFR A1298C mutation in the patient's mother, who did not show any symptoms associat­ ed with thrombophilic activity, and conditions during gestation may have affected the patient's condition.

Association of factor V Leiden, Janus kinase 2, prothrombin, and MTHFR mutations with primary Budd-Chiari syndrome in Egyptian patients.

Budd-Chiari syndrome (BCS) is defined as obstruction of hepatic venous outflow anywhere from the small hepatic veins to the suprahepatic inferior vena cava. The pathogenesis of BCS is still not fully understood. This study aimed to evaluate the association of factor V Leiden (FVL), Janus kinase 2 (JAK2), prothrombin, and methylene tetrahydrofolate reductase (MTHFR) mutations with primary BCS. The study was carried out on 35 patients with primary BCS and 15 age and gender matched healthy individuals as a control group. Genotyping of FVL, prothrombin, and MTHFR mutations was determined by GENEQUALITY AB-THROMBO TYPE kit based on the reverse hybridization principle. JAK2 mutation was determined by polymerase chain reaction-restriction fragment length polymorphism. There was a statistically significant difference between patients and controls regarding FVL, MTHFR C677T, and MTHFR A1298C mutations with odds ratio of 1.83, 2.0, and 1.79, respectively. Hetero MTHFR C677T, hetero FVL, and hetero MTHFR A1298C were the most common etiological factors being responsible for 57.1, 42.9, and 42.9% of primary BCS cases, respectively. It could be concluded that BCS is a multifactorial disease; in the current study, MTHFR C677T mutation was the most common cause of disease. Identification of one cause of BCS should not eliminate investigations for detection of other etiological factors.

Venous Thromboembolism after Allogeneic Pediatric Hematopoietic Stem Cell Transplantation: A Single-Center Study.

Objective:Venous thromboembolism (VTE) in children who undergo hematopoietic stem cell transplantation (HSCT) has high morbidity. The aim of this study is to assess the incidence of VTE in allogeneic pediatric HSCT recipients and the contribution of pretransplant prothrombotic risk factors to thrombosis.Materials and Methods:We retrospectively evaluated 92 patients between April 2010 and November 2012 undergoing allogeneic HSCT who had completed 100 days post-HSCT. Before HSCT, coagulation profiles; acquired and inherited prothrombotic risk factors including FV G1691A (factor V Leiden), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations; and serum homocysteine and lipoprotein (a), plasma antithrombin III, protein C, and protein S levels were obtained from all patients.Results:In the screening of thrombophilia, 8 patients (9%) were heterozygous for factor V Leiden, 5 (6%) were homozygous for MTHFR 677TT, 12 (14%) were homozygous for MTHFR 1298CC, and 2 (2%) were heterozygous for prothrombin G20210A mutation. We observed VTE in 5 patients (5.4%); a prothrombotic risk factor was found in 3 out of these 5 patients, while 4 out of 5 patients had central venous catheters. It was determined there was no significant relationship between VTE and inherited prothrombotic risk factors.Conclusion:VTE after HSCT seems to be a low-frequency event that may be due to low-dose, low-molecular-weight heparin prophylaxis, and the role of inherited prothrombotic risk factors cannot be entirely excluded without a prospective study.

Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency.

Folate deficiency is strongly associated with cardiovascular disease. We aimed to explore the joint effect of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G polymorphisms on folate deficiency in a Chinese hypertensive population. A total of 480 subjects aged 28–75 were enrolled in this study from September 2005–December 2005 from six hospitals in different Chinese regions. Known genotypes were detected by PCR-RFLP methods and serum folate was measured by chemiluminescence immunoassay. Our results showed that MTHFR 677TT and MTR 2756AG + GG were independently associated with a higher risk of folate deficiency (TT vs. CC + CT, p < 0.001 and AG + GG vs. AA p = 0.030, respectively). However, the MTHFR A1298C mutation may confer protection by elevating the serum folate level (p = 0.025). Furthermore, patients carrying two or more risk genotypes showed higher odds of folate deficiency than null risk genotype carriers, especially those carrying four risk genotypes. These findings were verified by generalized multifactor dimensionality reduction (p = 0.0107) and a cumulative effects model (p = 0.001). The results of this study have shown that interactions among homocysteine metabolism gene polymorphisms lead to dramatic elevations in the folate deficiency risk.

P202 – 2912: Methylenetetrahydrofolate reductase (MTHFR) polymorphisms A1298C and C677T as genetic risk factors for perinatal and childhood arterial ischemic stroke?

Objective The knowledge of arterial ischemic stroke (AIS) risk factors is still insufficient. Most frequently reported risk factors are cerebral arteriopathies, cardiac diseases, vascular malformations, infections, and traumas. Because of multifactorial etiology AIS might possibly have a multigenic inheritance pattern. The potential genetic risk factor for AIS could be the decreased activity of methylenetetrahydrofolate reductase (MTHFR), which is caused by common polymorphisms C677T (rs1801133) and A1298C (rs1801131). The aim of the study is to examine the role of these two MTHFR polymorphisms in searching for genetic determinants in arterial ischemic stroke. Methods 78 randomly selected pediatric stroke patients, 50 with perinatal and 28 with childhood stroke, participated in the study. Population-based control-group for perinatal stroke consisted of 150 and for childhood stroke of 84 healthy individuals. DNA testing for MTHFR C677T and A1298C mutations was performed, genotypes were determined by PCR using specific primers. Association analysis (p-values with Fisher exact test, odds ratios with 95% confidence intervals) was performed using Terminal software. Results The 677T allele carrier status (p=0.9, OR=1.0) did not show relevance as a genetic risk factor for perinatal stroke. An interesting observation was the fact that minor allele frequency of A1298C was higher in healthy controls than in patients with either perinatal (p=0.08, OR=0.63) or childhood (p=0.14, OR=0.6) AIS. On the other hand, minor allele frequency of C677T demonstrated a weak association with childhood AIS (p=0.09, OR=1.7, 95% CI: 0.9–3.2). Conclusion Our data support the hypothesis that functional MTHFR polymorphism C677T may represent a genetic risk factor for childhood AIS, representing 1.7-times higher risk. The A1298C polymorphism was not found as genetic risk factor for perinatal nor for childhood stroke.

Mo2021 The Role of Hypercoagulability in Ischemic Colitis

Introduction: Ischemic colitis (IC) is one of the most common gastrointestinal vascular diseases in the world. IC can result from alterations in the systemic circulation or from anatomic or functional changes in the mesenteric vasculature. On the other hand, an increasing diversity of causes of IC has been reported, including hematologic disorders, thrombophilic conditions, and medications. The aim of this study is to evaluate the role of thrombophiliahypercoagulability in IC. Methods: A prospective study of 56 patients with IC (diagnosis was established from clinical, endoscopic and pathologic (biopsy proven or compatible with IC) findings) who were evaluated for protein C (PC), protein S (PS), antithrombin (AT), resistance to activated protein C (APCR), lupus anticoagulant (LA), factor V G1691Amutation (FV Leiden), prothrombin G20210A mutation, methylenetetrahydrofolate reductase (MTHFR) gene C677T & A1298C mutations and plasminogen activator inhibitor-1 (PAI1) gene 5G/4G & 4G/4G polymorphisms. The results were compared with 44 controls with known predisposing factors (including history of thrombosis, atherosclerosis, hypertension, chronic renal insufficiency, diabetes mellitus, irritable bowel syndrome, chronic constipation, history of abdominal aorta aneurysm, history of schock and autoimmune disease) but no evidence of IC. Results: Low levels of PC and AT (p= .064 & p= .022, respectively), low levels of APCR (normal: >2, p = .008) and high levels of fibrinogen (p= .0005) were recorded in IC group. Homozygotes for MTHFR A1298C & C677T mutations tended to be more in the group with IC (χ2(2)= 5.582, p = .061 & χ2(2)= 1.291, p= .525, respectively). Furthermore, the prevalences of 5G/4G & 4G/4G polymorphisms were elevated in the patients group (χ2(2)= 6.973, p = .031), while the incidence of LA positives was higher in the same group (p = .037, FET). Multivariate analysis was performed to determine the effects of prothrombotic factors in IC. 5G/4G polymorphism of PAI-1 gene (OR 12.29; 95% CI 2.2667.00), APCR (OR .089; 95% CI 0.011-0.699) and fibrinogen (OR 1.013; 95% CI 1.0031.023) were determined as predictors of IC. (FET: Fischer's Exact Test, OR: Odds ratio, CI: Confidence intervals). Conclusions: This study suggests that hypercoagulability, hereditary or acquired, plays an essential role in the manifestation of IC.

The role of hypercoagulability in ischemic colitis

Objective. The aim of this study is to evaluate the role of thrombophilia-hypercoagulability in ischemic colitis (IC). Material and methods. Thrombophilia and fibrinogen were evaluated in 56 cases of IC and 44 controls with known predisposing factors but no evidence of IC. Thrombophilic factors tested were: protein C (PC), protein S, antithrombin (AT), resistance to activated protein C (APCR), lupus anticoagulant (LA), factor V G1691A mutation (FV Leiden), prothrombin G20210A mutation, methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C mutations and plasminogen activator inhibitor-1 (PAI-1) gene 5G/4G and 4G/4G polymorphisms. Results. In IC group were recorded: i) low levels of PC and AT (p = 0.064 and p = 0.022, respectively); ii) low levels of APCR (normal: >2, p = 0.008); iii) high levels of fibrinogen (p = 0.0005); iv) higher number of homozygotes for MTHFR A1298C and C677T mutations (p = 0.061 and p = 0.525 (Pearson chi-square), respectively); v) greater prevalence of 5G/4G and 4G/4G polymorphisms (p = 0.031 (Pearson chi-square)) and vi) higher incidence of LA-positive individuals (p = 0.037, Fischer’s exact test). Multivariate analysis was performed to determine the effects of prothrombotic factors in IC. 5G/4G polymorphism of PAI-1 gene (odds ratio (OR) 12.29; 95% confidence interval (CI) 2.26–67.00), APCR (OR 0.089; 95% CI 0.011–0.699) and fibrinogen (OR 1.013; 95% CI 1.003–1.023) were determined as predictors of IC. Conclusions. This study suggests that hypercoagulability, hereditary or acquired, plays an essential role in the manifestation of IC.

Association study of methylenetetrahydrofolate reductase A1298C mutation with cerebral venous thrombosis risk in an Iranian population.

Background:Cerebral venous thrombosis (CVT) is an uncommon condition characterized by severe clinical manifestations and high mortality rate. There is limited data on the role of methylenetetrahydrofolate reductase (MTHFR) A1298C mutation as a risk factor for CVT development in Iranians.Aim:The aim was to investigate a possible association between fasting plasma homocysteine (Hcy) levels, MTHFR A1298C mutation, and CVT in Iranian population.Materials and Methods:The study population consisted of 50 patients with a diagnosis of CVT (20–63 years old) and 75 healthy subjects (18–65 years old) as control. Genotyping of the MTHFR A1298C mutation and Hcy measurement was carried out by polymerase chain reaction-restriction fragment length polymorphism technique and enzyme immunoassay method, respectively.Results:Fasting plasma total Hcy levels were significantly higher in CVT patients than controls (P = 0.015). No significant differences were observed in the MTHFR A1298C genotypes frequency between CVT patients and controls (P > 0.05). The frequency of the 1298C allele was 36% and 37.5% in CVT patients and controls, respectively and did not differ significantly between the two groups (P = 0.16).Conclusions:Our study demonstrated that MTHFR A1298Cmutation is not a significant risk factor for CVT.

Association of methylenetetrahydrofolate reductase polymorphisms with susceptibility to Alzheimer's disease

BackgroundGenetic risk factors play an important role in the pathogenesis of Alzheimer's disease (AD). In this case-control study, we examined the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and their correlation with this pathology. ObjectiveTo verify the association between MTHFR C677T and A1298C polymorphisms and Alzheimer's disease. MethodThis work was conducted as a case–control study. Cases consisted of thirty-eight patients and 100 individuals without dementia constituted the control group. Genotyping of MTHFR polymorphisms was performed on patients and controls. ResultGenetic analyses did not indicate a significant association between the MTHFR C677T mutation and AD (C/T: 63.15% versus 39%, p=0.087). However, the genotype prevalence of the missense variant MTHFR A1298C was significantly different between patients and controls (A/C: 55% versus 7%, p<10−3). Our data suggest an association between the MTHFR A1298C mutation and AD; however, the MTHFR C677T mutation did not contribute to susceptibility for AD. ConclusionThe MTHFR A1298C polymorphism is a possible risk factor for Alzheimer's disease.

Thrombophilic Mutations in Iranian Patients With Thrombophilia

Objectives To investigate the frequency and type of Factor V Leiden (FVL), prothrombin, and methylenetetrahydrofolate reductase (MTHFR) mutations in ethnic Iranian patients and to evaluate the correlation between platelet count and thrombotic mutations. Methods This descriptive epidemiologic case study was performed with 208 patients with thrombotic disorders and hemorrhaging who were referred to Payvand Medical and Specialty Laboratory in Tehran, Iran, from 2007 through 2010. Peripheral blood samples from patients with abnormal thrombosis were analyzed for FVL, prothrombin G20210A, and MTHFR (A1298C and C677T) mutations, respectively. Mutation analysis was accomplished by polymerase chain reaction (PCR)–reverse dot blot. Platelet counts were obtained by automated cell count. Results Thrombophilic mutations were observed in 105 cases of 208 patients, including 13 patients with FVL, 51 patients with MTHFR C677T mutation, 33 patients with MTHFR A1298C mutation, and 8 patients with prothrombin G20210A mutation. Eighteen patients showed 2 simultaneous mutations and 3 patients showed 3 simultaneous mutations. According to our results, platelet counts were in normal range, so no statistically significant difference was observed between platelet count and mutation type. Conclusions The frequency of MTHFR C677T mutation is higher than that of FVL and/or prothrombin 20210A mutations in ethnic Iranian patients with thrombophilia. Also, thrombophilic mutations were not observed to have any effect on platelet count in patients with thrombophilia. Regarding the high prevalence of MTHFR C677T mutation in our region, family members of any patient with the MTHFR C677T mutation should be screened to identify this genetic mutation. * Abbreviations : FVL : Factor V Leiden APC : activated protein C MTHFR : methylene-tetrahydrofolate reductase EDTA : ethylenediaminetetraacetic acid PCR : polymerase chain reaction SSOP : sequence-specific oligonucleotide probes BCIP : 5-bromo-4-chloro-3-indolyl phosphate NBT : nitro blue tetrazolium PT : partial thrombosis PLT : platelet RFLP : restriction fragment length polymorphism BP : base pair

Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: A meta-analysis

BackgroundRecurrent pregnancy loss is an important clinical problem. Recently, high-level homocysteine in blood has been considered as a possible cause. Genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) have been proved to be the common hereditary factors of high-level homocysteine. The association between MTHFR polymorphisms and unexplained recurrent pregnancy loss (URPL) has been reported but with controversial results. The purpose of present study is to collect and analyze published available data, and evaluate the association between MTHFR polymorphisms and URPL. MethodsA meta-analysis was performed to examine the association between MTHFR polymorphisms (C677T and A1298C) and URPL. Odds ratio (OR) and its 95% confidence interval (CI) were used in each study of genotype and allele contrast. Result(s)MTHFR C677T: The analysis included 3559 URPL cases and 5097 healthy controls. Overall random-effects odds ratios (ORs) were 1.68 (95% CI, 1.32–2.13; P<0.0001) for TT versus total genotypes, 1.35 (95% CI, 1.04–1.76; P=0.0224) for TT and CT genotype combined versus total genotypes and 1.34 (95%CI, 1.13–1.58; P<0.0001) for T versus total alleles. Although significant heterogeneity was found in C677T, it became weaker in the East Asian subgroup and the mixed subgroup when separated by ethnic subgroups. The results showed significant association between MTHFR C677T and URPL in the East Asian subgroup (ORs 2.11 for TT versus total genotype (P=0.0004) and 1.53 for T versus total alleles (P<0.0001)) and in the mixed subgroup (ORs 3.47 for TT versus total genotypes (P<0.0001) and 1.80 for T versus total alleles (P<0.027)), but not in Caucasian subgroup. MTHFR A1298CThe study involved 1163 URPL cases and 1061 healthy controls. Overall random-effects odds ratios (ORs) were 1.37 (95% CI, 0.71–2.67; P=0.3456) for CC versus total genotypes, 1.16 (95%CI, 0.98–1.38; P=0.0833) for CC+AC versus total genotypes and 1.04 (95%CI, 0.84–1.29; P=0.7112) for C versus total alleles. No significant association between MTHFR A1298C polymorphism and URPL was found. ConclusionsThese results indicate a significant association between MTHFR C677T mutation and URPL in the East Asian subgroup and mixed subgroup, but no significance in MTHFR A1298C mutation.

Cerebral sinovenous thrombosis associated with MTHFR A1298C mutation in the newborn: a case report

Although cerebral sinovenous thrombosis (CSVT) is a rare condition in the neonatal period, high rates of morbidity and mortality necessitate the establishment of an early diagnosis. Methylenetetrahydrofolate reductase (MTHFR) plays a central role in the folate cycle and mutations of MTHFR are associated with vascular disease. While the C677T common missense mutation is the most well-defined MTHFR polymorphism, another common missense mutation, A1298C also exists. There has been no reported case of CSVT associated with MTHFR A1298C mutation in the neonatal period. Herein, we report a neonate with CSVT who was found to have MTHFR A1298C homozygosity.

Effect of Prothrombotic Mutations on Factor Consumption in Children With Hemophilia

In hemophilia A, factor activity usually correlates with clinical severity; however, there are patients with severe hemophilia who have bleeding less than expected. The aim of this study is to evaluate the impact of prothrombotic mutations on annual factor consumption in children with hemophilia. Factor V Leiden (FVL) G1691A, Prothrombin (PT) G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T and A128C mutations were evaluated in children with moderate-severe hemophilia A (n = 51) and controls (n = 25). None of the cases and controls carried the FVL and PT G20210A in homozygous state. There was no difference in factor consumption between carriers of FVL, PT mutations, and noncarriers. Patients who were homozygous for MTHFR C677T were found to have increased factor consumption compared to noncarriers, and this was a negative association. No decrease in factor consumption was noted in patients with hemophilia having MTHFR A1298C mutation. We could not demonstrate a significant decrease in factor concentrate consumption in children with hemophilia having prothrombotic mutations.

Methylenetetrahydrofolate Reductase Gene Polymorphisms in Egyptian Women with Unexplained Recurrent Pregnancy Loss

This work aims at testing for the association of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with unexplained recurrent pregnancy loss (RPL) among Egyptian women. Participants were 70 cases having a history of two or more events of unexplained RPL and 136 controls with a good obstetric history. Detection of MTHFR C677T and A1298C mutations was done by polymerase chain reaction with restriction fragment length polymorphisms assay using restriction enzymes HinfI and MboII respectively. Compared with controls, cases with unexplained pregnancy loss showed higher frequency of the homozygous mutant MTHFR 677 TT, 1298 CC genotypes, and the mutant haplotype 677T/1298C, although not reaching statistical significance. The frequency of 677 mutant genotypes (TT or TC) combined with either the mutant 1298 (CC or AC) or normal 1298 (AA) genotypes was significantly increased among cases with late-stage pregnancy loss versus those with early-stage pregnancy loss (p=0.001). There was also increased frequency of the 677 mutant genotypes among cases with secondary infertility compared with those with primary infertility and among cases with pregnancy loss >4 times compared with those with ≤4 times but with no statistical significance. Regarding other risk factors, it was noted that the frequency of mutations among cases with no or just one risk factor did not differ significantly from those having two or more risk factors (p=0.98). Mutations related to the MTHFR gene are increased but not statistically significant in Egyptian women with unexplained pregnancy loss. Interaction with other genetic variants might be speculated and need to be investigated.

The A1298C Mutation in Methylenetetrahydrofolate Reductase Gene and Its Association With Idiopathic Venous Thrombosis in an Iranian Population

Background: Venous thrombosis (VT) is an important cause of mortality and morbidity resulting from acquired and inherited factors. The A1298C mutation of the methylenetetrahydrofolate reductase (MTHFR) gene remains a controversial risk factor for VT. In this study we investigated a possible association between A1298C mutation in the MTHFR gene and fasting hyperhomocysteinemia with VT. Materials and Methods: The study was comprised of 200 patients with a diagnosis of VT and 100 healthy subjects as a control. A1298C mutation analysis was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and homocysteine measurement was carried out by enzyme immunoassay. Results: The prevalence of A1298C genotypes between patients and controls was almost similar (P=0.9). The frequency of the 1298C allele was 38.5% and 36.5% in patients and controls, respectively, and did not differ significantly between the 2 groups (odds ratio [OR], 0.811, 95% CI [0.566-1.183], P=0.29). The fasting plasma total homocysteine level was significantly higher in patients than controls (P=0.001). Conclusions: We concluded that hyperhomocysteinemia but not MTHFR A1298C mutation is a significant risk factor for VT in the Iranian population.