Methylenetetrahydrofolate Reductase C677T Mutation Research Articles

Homocysteine and Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities Study and the Multi-Ethnic Study of Atherosclerosis

Although many studies have investigated the association of blood homocysteine with major cardiovascular diseases such as coronary heart disease and stroke, research on its association with atrial fibrillation (AF) is scarce. We analysed data from Atherosclerosis Risk in Communities (ARIC) Study (n=492, age 45-64 years) and Multi-Ethnic Study of Atherosclerosis (MESA) (n=6,641, age 45-84 years). During the 10,106 and 67,613 person-years of follow-up, we identified 85 and 351 AF events in ARIC and MESA, respectively. An age-, sex-, and race-adjusted model showed dose-response relations between plasma homocysteine concentrations and AF incidence in both ARIC and MESA. Further adjustments for other AF risk factors did not change the associations. In the fully adjusted model, a meta-analysis of both studies showed a significant association between homocysteine and AF [hazard ratio (95% confidence interval) per 1 unit increment in log2(homocysteine), 1.27 (1.01-1.61)]. Individuals with higher levels of all three B vitamins (vitamin B6 and B12, and folate) had a lower risk of AF, but those associations were not statistically significant. In the full ARIC cohort [n=12,686 (2079 AF events)], there was no association between the C677T methylenetetrahydrofolate reductase (MTHFR) mutation and AF. In the prospective population-based ARIC and MESA cohorts, elevated homocysteine was modestly associated with an increased risk of incident AF, but the C677T MTHFR mutation was not associated with AF risk, suggesting that homocysteine may be a novel risk marker for AF rather than a causal risk factor.

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.

Commonness of Factor V Leiden, Prothrombin G20210A and Methylenetetrahydrofolate Reductase C677T Mutations among Patients with Thromboembolism in the Western Black Sea (Zonguldak) Region of Turkey

Commonness of Factor V Leiden, Prothrombin G20210A and Methylenetetrahydrofolate Reductase C677T Mutations among Patients with Thromboembolism in the Western Black Sea (Zonguldak) Region of Turkey

The incidence of FVL and PT G20210A mutations in patients with idiopathic deep venous thrombosis

Background: Factor V Leiden (FVL), prothrombin gene (PT G20210A), and methylenetetrahydrofolate reductase (MTHFR) C677T mutations are known as molecular biomarkers to evaluate the predisposition of deep venous thrombosis (DVT). These hereditary risk factors affect the natural anticoagulant mechanisms and activate the coagulation mechanisms because of an imbalance between procoagulant and anticoagulant factors. Our study aimed to determine the prevalence of these mutations in Turkish patients presenting with idiopathic DVT. Methods: A total of 135 patients with idiopathic DVT admitted to our clinic were investigated for FVL, PT G20210A, and MTHFR (C677T, A1298C) gene mutations. Screening of polymorphisms was carried out by using SNaPshot® multiplex system (Applied Biosystems Inc.). Wild, heterozygous and homozygous genotypic distributions of these mutations were defined as number and percentage frequency. Results: There were 74 male and 61 female patients ranging in age from 18 to 85 years. FVL mutation was found in 66 (41.47%) patients (12 homozygotes 8.88%, 44 heterozygotes 32.59%), PT G20210A was found in 14 (10.36%) patients (1 homozygous 0.74%, 13 heterozygotes 9.62%). MTHFR C677T was found in 53 (39.25%) patients (10 homozygotes 7.40%, 43 heterozygotes 31.85%), and MTHFR A1298C was found in 84 (62.22%) patients (16 homozygotes 11.85%, 68 heterozygotes 50.37%).

Prevalence of the MTHFR C677T Mutation in Fertile and Infertile Women.

Introduction The importance of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in infertile women remains controversial. Objective To evaluate if the MTHFR C677T mutations are more frequent in infertile women, and if they can be associated with the occurrence of infertility in the Brazilian population. Methods This case-control study included 130 infertile women consulting at a private clinic between March 2003 and March 2005 (data previously published), and 260 fertile women attending the family planning outpatient clinic of our institution between April 2012 and March 2013. Data analysis The Chi-squared and Fisher Exact tests were used to evaluate the association between the presence of the MTHFR C677T mutation and a history of infertility. Results The frequency of the mutation was of 58.5% for the case group (n = 76) and of 49.2% for the fertile controls (n = 128). The mutation was homozygous in 13 women in the case group (10%) and in 23 of the fertile women in the control group (8.8%). These differences were not statistically significant. Conclusions These results suggest that the presence of the MTHFR C677T mutation does not constitute a risk factor for infertility, even when the mutation is homozygous. Further studies are needed to confirm whether research on this mutation should be considered unnecessary in women with infertility.

Rivaroxaban as an effective alternative to warfarin in a patient with atrial fibrillation, thrombophilia, and left atrial appendage thrombus: a case report

BackgroundAtrial fibrillation is the most common cardiac arrhythmia. It is responsible for up to 20% of all ischemic strokes. Rate control and anticoagulation are crucial for atrial fibrillation management and stroke prevention.Case presentationWe present the case of an 84-year-old Italian woman with a left atrial appendage thrombus that developed despite her use of anticoagulant therapy with warfarin for a previous pulmonary embolism. She had atrial fibrillation and heterozygosity for both factor V Leiden and methylenetetrahydrofolate reductase C677T mutation, thus creating resistance to activated protein C. Anticoagulant therapy was switched to heparin for 1 week and then to rivaroxaban. After 3 months of rivaroxaban use, the thrombus disappeared.ConclusionsThis case raises the issue of the ineffectiveness of warfarin therapy in complex cases involving particular thrombophilic conditions and the possibility of using rivaroxaban as a safe and effective alternative.

Genetic polymorphism of MTHFR C677T with preterm birth and low birth weight susceptibility: a meta-analysis.

This study aimed at clarifying the association of maternal and neonatal methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms with preterm birth (PTB) and low birth weight (LBW) susceptibility, respectively. A systematic search of Embase, Medline, China Biological Medicine Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang Database was performed before June, 2016. The frequencies of maternal and neonatal MTHFR C677T genotypes in the cases and controls and other information were extracted by two independent investigators. Odds ratios (ORs) with 95% confidence intervals (CIs) were adopted to estimate the relationships between MTHFR C677T polymorphisms and PTB as well as LBW by random or fixed effect models. Twenty-five studies from 20 articles concerning maternal and neonatal MTHFR C677T gene polymorphism with PTB and LBW were included in this study. Maternal MTHFR C677T polymorphism was associated with PTB risk under allele contrast (T vs. C, OR = 1.36, 95% CI 1.02-1.81), homozygote (TT vs. CC, OR = 1.70, 95% CI 1.07-2.68), and recessive (TT vs. CT + CC, OR = 1.49, 95% CI 1.00-2.22) model, but not dominant or heterozygote model. Maternal MTHFR C677T polymorphism was also associated with LBW risk under allele contrast (OR = 1.69, 95% CI 1.25-2.28), homozygote (OR = 2.26, 95% CI 1.44-3.54), dominant (OR = 1.71, 95% CI 1.19-2.47), recessive (OR = 1.79, 95% CI 1.42-2.26) model, but not heterozygote model. No associations between neonatal MTHFR C677T polymorphism and PTB or LBW were found under all genetic models. Identification of maternal MTHFR C677T mutation may play a key role for primary prevention of PTB as well as LBW and screening pregnant women of high risk in developing countries.

The MTHFR C677T mutation is not a risk factor recognized for HBV-related HCC in a population with a high prevalence of this genetic marker

BackgroundPolymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene can affect disease progression in HBV infection. However, the results from different reports are inconsistent. The aim of this study was to investigate the association between the MTHFR C677T polymorphism and the outcome of HBV infection in a Tianjin Han population. MethodsTaqMan SNP genotyping was employed to determine the alleles and genotypes of MTHFR C677T in 2511 subjects from various stages of HBV infection and 549 healthy controls. ResultsOf the 3060 subjects, the genotypic frequencies were CT 48.9%, TT 29.3% and CC 21.8%; the allelic frequencies were T 53.8% and C 46.2%. There was no significant difference in genotypic or allelic distribution among the different disease groups. When either healthy subjects or self-limited subjects were used as controls, the TT genotype and the T allele conferred protective effects against hepatocellular carcinoma (HCC) (HCC vs healthy subjects: OR=0.588, 95% CI=0.413–0.836, P=0.003; OR=0.768, 95% CI=0.645–0.915, P=0.003, respectively. HCC vs self-limited subjects: OR=0.598, 95% CI=0.404–0.886, P=0.010; OR=0.772, 95% CI=0.635–0.940, P=0.010, respectively). After sub-stratification by gender, the prevalence of the TT genotype or T allele was the lowest in the male HCC group (TT 23.5%, T 49.8%). The protective effects of the TT genotype and the T allele were observed in male HCC and cirrhotic subjects (HCC vs self-limited subjects: OR=0.470, 95% CI=0.288–0.766, P=0.002; OR=0.681, 95% CI=0.535–0.866, P=0.002, respectively. Liver cirrhosis vs self-limited subjects: OR=0.624, 95% CI=0.392–0.992, P=0.046; OR=0.791, 95% CI=0.627–0.998, P=0.048, respectively), but not in female. When the subjects were stratified according to the clinical features, no statistically significant difference in the genotypic distribution was observed (P>0.05). ConclusionsThe TT genotype and T allele of MTHFR C677T may confer a protective effect on disease progression to HCC in HBV-infected individuals, especially among male patients, in a population with a high prevalence of this genetic marker.

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.

Individual and Joint Associations of Methylenetetrahydrofolate Reductase C677T Genotype and Plasma Homocysteine With Dyslipidemia in a Chinese Population With Hypertension.

We aimed to examine the cross-sectional associations of plasma total homocysteine (tHcy) concentrations and methylenetetrahydrofolate reductase ( MTHFR) C677T genotype with dyslipidemia. A total of 231 patients with mild-to-moderate essential hypertension were enrolled from the Huoqiu and Yuexi communities in Anhui Province, China. Plasma tHcy levels were measured by high-performance liquid chromatography. Genotyping was performed by TaqMan allelic discrimination technique. Compared with MTHFR 677 CC + CT genotype carriers, TT genotype carriers had higher odds of hypercholesterolemia (adjusted odds ratio [OR] [95% confidence interval (CI)]: 2.7 [1.4-5.2]; P = .004) and higher odds of abnormal low-density lipoprotein cholesterol (adjusted OR [95% CI]: 2.3 [1.1-4.8]; P = .030). The individuals with the TT genotype had higher concentrations of log(tHcy) than those with the 677 CC + CT genotype (adjusted β [standard error]: .2 [0.03]; P < .001). Patients with tHcy ≥ 10 μmol/L had significantly higher odds of hypercholesterolemia (adjusted OR [95% CI]: 2.4 [1.2-4.7]; P = .010). Furthermore, patients with both the TT genotype and the tHcy ≥ 10 μmol/L had the highest odds of hypercholesterolemia (adjusted OR [95% CI]: 4.1 [1.8-9.4]; P = .001) and low-density lipoprotein cholesterol (adjusted OR [95% CI]: 2.4 [1.0-6.0]; P = .064). This study suggests that both tHcy and the MTHFR C677T gene polymorphism may be important determinants of the incidence of dyslipidemia in Chinese patients with essential hypertension. Further studies are needed to confirm the role of tHcy and the MTHFR C677T mutation in the development of dyslipidemia in a larger sample.

The effect of the MTHFR C677T mutation on athletic performance and the homocysteine level of soccer players and sedentary individuals.

This study investigated athletic performance and homocysteine (Hcy) levels in relation to the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and explored the relationship between this mutation and other cardiac risk factors in soccer players and sedentary individuals. The study groups consisted of randomly selected soccer players (n=48) from the Turkish Super and Major League and sedentary male students (n=48) aged 18-27. Anthropometric variables, aerobic and anaerobic thresholds were measured, furthermore, biochemical assays were performed. The level of HDL cholesterol, LDL cholesterol, triglyceride, Hcy, folate, vitamin B12, hemogram and MTHFR C677T was investigated. The results showed that there was a statistical difference between the two groups in terms of body mass, body fat, the BMI, the aerobic threshold heart rate (ATHR), aerobic threshold velocity (ATVL) and anaerobic threshold velocity (ANTVL). The soccer players were found to have lower levels of triglyceride, total cholesterol and LDL cholesterol, and higher levels of folate than the sedentary participants. The analysis of the alleles of the MTHFR C677T polymorphism showed that the participants that carried TT genotypes had a lower level of vitamin B12 and folate, and a higher level of Hcy than the participants carrying CC and CT genotypes. In conclusion, the baseline homocysteine and cardiovascular fitness levels of healthy young males with the TT genotypes of the MTHFR C677T genotype were found to strongly correlate with their levels of Hcy.

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.

Association study of methylenetetrahydrofolate reductase C677T mutation with cerebral venous thrombosis in an Iranian population.

There are limited data on the role of methylenetetrahydrofolate reductase C677T polymorphism and hyperhomocysteinemia as risk factors for cerebral venous thrombosis in Iranian population. We examined a possible association between fasting plasma homocysteine levels, methylenetetrahydrofolate reductase C677T polymorphism, and cerebral venous thrombosis in 50 patients with a diagnosis of cerebral venous thrombosis (20-63 years old) and 75 healthy controls (18-65 years old). Genotyping of the methylenetetrahydrofolate reductase C677T gene polymorphism was performed by PCR-restriction fragment length polymorphism analysis, and homocysteine levels were measured by enzyme immunoassay. Fasting plasma homocysteine levels were significantly higher in cerebral venous thrombosis patients than in controls (P = 0.015). Moreover, plasma homocysteine levels were significantly higher in methylenetetrahydrofolate reductase 677TT genotype compared to 677CT and 677CC genotypes in both cerebral venous thrombosis patients (P = 0.01) and controls (P = 0.03). Neither 677CT heterozygote genotype [odds ratio (OR) 1.35, 95% confidence interval (CI) 0.64-2.84, P = 0.556] nor 677TT homozygote genotype (OR 1.73, 95% CI 0.32-9.21, P = 0.833) was significantly associated with cerebral venous thrombosis. Additionally, no significant differences in the frequency of 677T allele between cerebral venous thrombosis patients and controls were identified (OR 1.31, 95% CI 0.69-2.50, P = 0.512). In conclusion, our study demonstrated that elevated plasma homocysteine levels are significant risk factors for cerebral venous thrombosis. Also, methylenetetrahydrofolate reductase 677TT genotype is not linked with cerebral venous thrombosis, but is a determinant of elevated plasma homocysteine levels.

Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis.

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses before the 20th week of gestation with the same partner. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms were reported to have an effect on embryonic development and pregnancy success. To clarify the effects of MTHFR polymorphisms on the risk of RPL in the Chinese population, a meta-analysis was performed. Related studies were identified from Medline, Embase, Web of Science, and Chinese Databases up to March 7th, 2015. We extracted the number of both C677T and A1298C genotypes in the cases and controls. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to estimate the associations. Data analysis was performed using Stata 13.1. Sixteen articles involving 1420 RPL cases and 1408 controls were included in this meta-analysis. MTHFR C677T polymorphism was significantly associated with RPL risk under dominant (TT+CT vs. CC; OR 2.10, 95% CI 1.76-2.50), recessive (TT vs. CC+CT; OR 2.36, 95% CI 1.92-2.90), heterozygote (CT vs. CC; OR 1.77, 95% CI 1.32-2.37), homozygote (TT vs. CC; OR 3.55, 95% CI 2.76-4.56), and additive (T vs. C; OR 1.83, 95% CI 1.64-2.05) model. Sensitivity analyses excluding studies that deviated from HWE did not change the direction of effect. For the A1298C mutation, no significant association was found. The Egger's regression asymmetry test showed no significant publication bias. Identification of MTHFR C677T mutation would have some implication for primary prevention of RPL and screening of high-risk individuals in China. Large well-designed researches are needed to fully describe the associations.

Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin.

Hyperhomocysteinemia and vitamin B12 deficiency may be involved in the development of diabetic peripheral neuropathy (DPN). Metformin therapy may reduce vitamin B12 plasma levels, thus contributing to DPN. The purposes of this cross-sectional study were to assess (1) the potential associations of DPN with serum levels of homocysteine (tHcy), B-vitamins, and/or the common methylenetetrahydrofolate reductase (MTHFR) C677T mutation; (2) the influence of chronic treatment with metformin on tHcy and B-vitamins concentrations and, finally, (3) to evaluate whether, by this influence, metformin is a risk factor for DPN in a group of type 2 diabetic outpatients. Our data showed that fasting tHcy, folate, and vitamin B12 levels and the MTHFR C677T genotype distribution were comparable between subjects with (n = 79, 30 %) and without DPN (n = 184, 70 %). Metformin-treated subjects (n = 124, 47 %) showed significantly lower levels of vitamin B12 (P < 0.001), but the prevalence of DPN was not different when compared to those not treated with this drug (33 vs. 27 %, P = NS). At univariate regression analysis, DPN was associated with age, duration of diabetes, HbA1c, creatinine levels, and the presence of coronary heart disease (CHD), and negatively with HDL-C concentrations (P < 0.05 all), but at multivariate regression analysis, high creatinine levels (P = 0.06), low HDL-C levels (P = 0.013), and a higher prevalence of CHD (P = 0.001) were the only variables independently associated with DPN in this population. In conclusion, in these type 2 diabetic outpatients circulating levels of tHcy, folate, and the MTHFR C677T mutation are not associated with DPN, which was predicted by creatinine levels, CHD, and dyslipidemia. Metformin therapy is associated with a mild vitamin B12 level reduction, but not with DPN.

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.

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.