Methylenetetrahydrofolate Reductase C677T Mutation Research Articles

Inherited Thrombophilia and Risk of Thrombosis in Children with Cancer: a Single-center Experience.

Thrombosis is an increasingly recognized complication of childhood malignancy and its treatment. The incidence and etiology of pediatric cancer-related thrombosis is still not well understood. The aim of this study was to evaluate the prevalence of common prothrombotic genetic conditions in children with cancer, the frequency of thrombosis, and the role of inherited thrombophilia in the development of thrombosis in a pediatric oncology population. Forty-seven children (36 treated for hematological malignancies and 11 for solid tumors) with a median age of 8.8. years (range 0.4 - 19.3 years) were included in the study. Genetic polymorphisms of Factor V Leiden (G1691A), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T were determined by real-time polymerase chain reaction-based DNA analysis. Four (8.5%) patients were heterozygous for Factor V Leiden, 3 (6.4%) were heterozygous for prothrombin G20210A mutation, and 3 (6.4%) were homozygous for MTHFR C677T mutation. All patients had implanted central venous catheters. Four (8.5%) children had documented thrombosis, three of which were in the upper venous system. Two of the four patients with thrombosis had Factor V Leiden heterozygosity. Thrombosis is an important complication of childhood cancer. The risk of thrombosis may be increased in patients with Factor V Leiden. In the absence of consensus guidelines, our results support the recommendation for thrombophilia screening in children with cancer.

Central Retinal Vein Occlusion in 12-year-old Girl with Methylenetetrahydrofolate Reductase Mutation: A Case Report and Review of the Literature.

This case report describes a central retinal vein occlusion (CRVO) in a healthy 12-year-old girl who developed retinal neovascularization at 24 years of age. To our knowledge, this is the longest time between a reported pediatric CRVO event and neovascularization. The patient underwent a full history, physical exam, and laboratory workup to determine potential risk factors contributing to the vascular event. Fundus photos, optical coherence tomography and fluorescein angiography were performed throughout the patient's treatment course. Family history was non-contributory, but laboratory testing revealed a mildly elevated homocysteine level and homozygous C677T mutation in methylenetetrahydrofolate reductase. As a result, she was started on folate supplementation. The patient has had no further ocular or systemic thrombotic events to date. Pediatric patients presenting with CRVO should undergo a systemic workup and require long-term follow-up to avoid complications such as intraocular hemorrhage, tractional retinal detachments, and neovascular glaucoma.

Association of MTHFR C667T Polymorphism, Homocysteine, and B Vitamins with Senile Cataract.

Senile cataract has become the leading cause of visual impairment and even blindness in the world, but there are few reports on its relationship with methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. This study is aimed to investigate the correlation between MTHFR gene polymorphisms or its enzyme metabolites and senile cataract. From January 2019 to June 2020, 663 patients with senile cataract at the Mianyang Central Hospital were enrolled as the observation group, and 646 healthy subjects were randomly selected as the control group. MTHFR gene polymorphisms (i.e., CC, CT, or TT genotypes) and serum homocysteine (HCY), folic acid (FOL), vitamin B12 (VitB12), and vitamin B6 (VitB6) levels were detected. The mutation rate of MTHFR C677T and HCY levels in the observation group were significantly higher than those in the control group, whereas FOL, VitB12, and VitB6 were significantly lower. With an increase in the MTHFR C677T mutation, HCY showed an upward trend, whereas FOL and VitB12 showed a decreasing trend in both the observation and control groups. Multiple logistic regression analysis showed that HCY and FOL were associated with senile cataract and MTHFR mutations; VitB12 was only associated with senile cataract. Compared to that with the CC genotype, CT and TT genotypes were associated with an increased senile cataract risk. Monitoring MTHFR gene polymorphisms and changes in serum HCY, FOL, and VitB12 levels could provide references in predicting senile cataract.

[Relationship between MTHFR Gene Polymorphism(C677T) and Adverse Reactions of High-Dose Methotrexate in Pediatric Patients with Acute Lymphoblastic Leukemia].

To explore the effects of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism on the adverse reactions of high-dose methotrexate (MTX) in pediatric patients with acute lymphoblastic leukemia (ALL). A total of 69 children with ALL admitted to the department of Pediatrics of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from November 2018 to October 2020 were included in this study. The clinical data of the children were collected, leukocytes were isolated from their peripheral blood, and MTHFR genotyping was performed by digital fluorescence molecular hybridization techniques. The adverse reactions and plasma drug concentration of MTX were monitored during the chemotherapy. Moreover, the effect of MTHFR gene polymorphism on MTX adverse reactions and plasma drug concentration were analyzed. Among the middle and high risk children, compared with the wildtype group (CC genotype), patients with MTHFR C677T mutations (CT+TT genotypes) had a higher risk of leukopenia (OR=2.38), neutropenia (OR=2.2), anemia (OR=1.83) and hepatoxicity (OR=1.98). However, no significant difference was found in the MTX plasma concentration between the MTHFR C677T mutantion group and the wildtype group at different timepoints (24 h, 48 h and 72 h). Multivariate analysis revealed that the plasma concentration of MTX (48 h), clinical risk level of ALL and MTHFR C677T gene polymorphism were independent factors for the adverse reactions of high-dose MTX. The MTHFR C677T mutations may be associated with myelosuppression and hepatotoxicity in children with ALL after high-dose MTX treatment.

Methylenetetrahydrofolate Reductase 677T Allele Is a Risk Factor for Arterial Thrombosis in Chinese Han Patients with Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by the persistent presence of antiphospholipid antibodies (aPL) and thrombotic or obstetric events. Given the heterogeneity of the clinical manifestations, it is likely that genetic and acquired factors are involved in the pathogenesis of APS. The inherited polymorphisms of the thrombophilic gene, including methylenetetrahydrofolate reductase (MTHFR) C677T, type 1 plasminogen activator inhibitor (PAI-1) 4G/5G, factor V Leiden (FVL) G1691A, prothrombin (PT) G20210A, antithrombin (AT), and fibrinogen (Fg) polymorphisms, were analyzed in 67 aPL(+) patients from the Chinese Han population, including 41 APS patients and 26 persistent aPL carriers. The MTHFR C677T genotypes of 105 healthy controls, and the PAI-1 4G/5G polymorphism of 120 healthy controls, from the Chinese Han population were acquired for this study. Both the MTHFR C677T genotype (χ2 = 10.67, p = 0.004) and C/T allele distribution (χ2 = 5.92, p = 0.019) between the aPL(+) patients and healthy controls were found to be significantly different. Furthermore, we observed that the patients with at least one T allele had a higher risk of arterial thrombosis (CT vs. CC, OR 11.00, p= 0.025; CT + TT vs. CC, OR 10.27, p = 0.018). The C677T mutation of MTHFR is a risk factor for arterial thrombosis in Chinese Han patients with APS.

Relationship between Methylenetetrahydrofolate Reductase C677T Homozygous Mutation and Cerebral Small Vessel Disease Subtypes

Background: Neuroimaging detects cerebral small vessel disease (CSVD) subtypes, including infarction, asymptomatic lacunes, cerebral microbleeds, white matter hyperintensities (WMHs), and enlarged perivascular space. Methylenetetrahydrofolate reductase (MTHFR) plays an essential role in the metabolism of folic acid and homocysteine. The purpose of this study was to investigate the relationship between the MTHFR C677T mutation and CSVD subtypes.Methods: A total of 144 patients with acute ischemic stroke who visited the Korea University Guro Hospital between April 2020 and August 2020 were retrospectively reviewed. After excluding 24 patients, due to missing laboratory, clinical, or imaging information, a total of 120 patients were analyzed.Results: Among the 120 participants, 25% were included in the MTHFR C677T homozygous mutation group, which had significantly lower folic acid levels (6.24±4.21 ng/mL vs. 8.24±4.21 ng/mL, p=0.03) and higher total homocysteine levels (17.09±14.07 μmol/L vs. 9.65±3.19 μmol/L, p<0.01). Using multiple logistic regression analysis, the homozygous mutation (adjusted odds ratio [aOR]=4.29; 95% confidence interval [CI]=1.16–15.90) and age (aOR=1.06; 95% CI=1.01–1.11) were independently associated with moderate to severe WMHs. Additionally, moderate to severe WMHs were more frequent in the homozygous mutation group (86.7% vs. 66.7%, p=0.01). In a detailed analysis, the homozygous mutation group showed a significantly higher rate of moderate to severe periventricular WMH (PWMH) (86.7% vs. 65.6%, p<0.01).Conclusion: The MTHFR C677T homozygous mutation was positively correlated with moderate to severe PWMH subtypes of CSVD.

A Case of Budd-Chiari Syndrome Associated with Erythrocytosis and Homozygous MTHFR C677T Mutation

An erythrocytosis describes an increased erythrocyte, subclassified into relative due to hemoconcentration or absolute by an increase in erythrocyte mass, defined as an increase in hemoglobin concentration and/or hematocrit in the peripheral blood above the sex-specific normal range. Budd-Chiari Syndrome (BCS) is related to an obstruction of the hepatic venous flow leading to occlusion of hepatic veins and their tributaries. Genetic and environmental factors can interact for risk determination of venous thromboembolism. The risk associated with SNP 677C>T and 1298A>C of the methylenetetrahydrofolate reductase (MTHFR), 1691G>A of the Factor V Leiden (FVL) and 20210G>A of the prothrombin (FII) genes were investigated in many studies involving thrombosis. This case report describes the clinical, hematological and biochemistry data about a 48-year-old woman diagnosed with PV and a BCS associated, also carrying 677C>T SNP in homozygosity. The patient started therapy with phlebotomy, hydroxyurea and oral anticoagulant. Currently, she presents a better clinical and laboratory condition with normalized values of hematological and platelet indices. This case report aims to contribute with evidence of related comorbidities and makes it possible to report that genetic factors are involved since the patient's mother had already been diagnosed with absolute erythrocytosis in 2016 at 78 years old. For this main result, we understand that it is clear that a family genetic study can reveal clinical modifying factors in these patients, as there are different clinical severities in the family. Furthermore, we believe in the need for a greater number of randomized clinical trials to add better evidence to complement an ideal therapeutic approach in these patients.

Methylenetetrahydrofolate reductase polymorphisms as risk factors for retinal venous occlusive disease: A literature review

The role of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene in retinal vein occlusion (RVO) is a theme of discussion since the first reports of RVO in patients with MTHFR C677T mutation and without classic acquired risk factors for retinal vascular disease. The association between MTHFR polymorphisms and RVO has been studied over the last 20 years producing conflicting results. This review aims to summarize the literature concerning the role MTHFR polymorphisms as risk factors for RVO.

Combined Effect of MTHFR C677T and PAI-1 4G/5G Polymorphisms on the Risk of Venous Thromboembolism in Chinese Lung Cancer Patients.

Venous thromboembolism (VTE) is a common and potentially fatal complication in cancer patients. Although several genetic risk factors related to thrombophilia have been identified, their contributions for the occurrence of VTE in cancer patients have conflicting results. The aim of this study was to evaluated the gene polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor-1 (PAI-1) 4G/5G in lung cancer patients, with and without VTE, and the combined effect on the risk of VTE. 92 lung cancer patients diagnosed with VTE (VTE group) and 122 lung cancer patients without VTE (non-VTE group) were enrolled in the study. The gene polymorphisms were analyzed by the method of polymerase chain reaction-restriction fragment length polymorphism. Gene mutation of factor V Leiden was not detected both in non-VTE group and VTE group. The frequency of MTHFR C677T homozygous mutation in VTE group was 25.00%, higher than that in the non-VTE group without statistical difference. It was found that the PAI-1 4G4G genotype is associated with a higher risk of VTE (OR: 2.62, 95%CI: 1.19-5.75). Interestingly, the interaction between MTHFR C677T and PAI-1 4G/5G polymorphisms showed that the coexistence of the 2 homozygous mutation could further increase the risk of VTE. In conclusion, PAI-1 4G/5G polymorphism may be an increased risk factor for VTE among lung cancer patients in Chinese population. The homozygous MTHFR C677T mutation may be not a risk factor for VTE but increases the risk, accompanied with PAI-1 4G5G genotype.

Plasma Serotonin is Elevated in Adult Patients with Sudden Sensorineural Hearing Loss.

The roles of thrombophilia and cardiovascular risk factors in sudden sensorineural hearing loss (SSNHL) remain controversial. Cochlear microthrombosis and vasospasm have been hypothesized as possible pathogenic mechanisms of SSNHL. This article investigates the circulating serotonin and homocysteine levels besides thrombophilia screening in patients with idiopathic SSNHL. A total of 133 SSNHL patients and age- and sex-matched controls were investigated (discovery cohort). Measurement included common inherited natural coagulation inhibitors, factor VIII, von Willebrand factor (VWF), antiphospholipid antibodies, homocysteine, and serotonin (whole blood, platelet, and plasma) levels, along with frequent relevant genetic variants. A validation cohort (128 SSNHL patients) was studied for homocysteine and serotonin levels. In the discovery cohort, 58.6% of patients exhibited thrombophilia, of which most had a low to moderate titers of antiphospholipid antibodies and high levels of factor VIII/VWF. Twenty-seven patients (20%) had mild-to-moderate hyperhomocysteinemia or were homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Regarding serotonin, SSNHL patients had elevated whole blood levels that remained within the normal range and normal platelet content. However, approximately 90% patients of both cohorts had elevated plasma serotonin. Elevated plasma serotoninemia was accompanied by serotonylation of platelet rhoA protein. This study shows that increased plasma serotonin appears as a biomarker of SSNHL (specificity: ∼96%, sensitivity: ∼90%) and could participate in the pathophysiology of SSNHL.

Meta-analysis of the relationship between methylenetetrahydrofolate reductase C677T and A1298C polymorphism and venous thromboembolism in the Caucasian and Asian.

Recent years, it is a highly debated topic that whether methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and A1298C polymorphism could increase susceptibility to venous thromboembolism (VTE) in the Asian and Caucasian. Therefore, we expect to settle that controversy evidentially. Basic methods: Electronic databases (Pubmed, embase, Cochrane library, scopus, OvidSP, Wiley Online library, Springer link, EBSCO, Elsevier Science Direct, Google scholar) without date limitation were searched. Crude odds ratio (OR) along with 95% confidence interval (95% CI) was calculated to assess the association quantitatively. Finally, a total of 37 eligible studies were included, containing 31 for MTHFR C677T polymorphism and 6 for MTHFR A1298C polymorphism. The pooled results suggested that MTHFR C677T mutation may increase susceptibility to VTE in reverse recessive model (CC+CT vs TT): OR = 0.68 (0.56, 0.83), reverse dominant model (CC vs CT +TT): OR = 0.82 (0.72, 0.94), heterozygote model (CT vs TT): OR = 0.65 (0.52, 0.81), homozygote model (CC vs TT): OR = 0.73 (0.60, 0.89) and allele model (C vs T): OR = 0.80 (0.71, 0.90). Subgroup analysis about Asian also support that results, but Caucasian group not. In addition, MTHFR A1298C polymorphism may be not related to VTE in all genetic model. The results of meta-analysis indicated that MTHFR C677T polymorphism might increase the risk of VTE, especially in Asian population.

Methylenetetrahydrofolate reductase C677T polymorphism and toxicity to 5-FU-based chemotherapy in colorectal cancer

Purpose: To investigate the toxicity of methylenetetrahydrofolate reductase (MTHFR) polymorphism in colorectal cancer patients treated with 5-fluorouracil (5-FU).Methods: A total of 105 patients with colorectal cancer who underwent 5-FU therapy were included in this study. MTHFR C677T polymorphisms were determined using direct sequencing. Physical examination and the results of blood and urine tests were used to evaluate the toxicities, including gastrointestinal toxicity, hematopoietic toxicity, hair-skin toxicity and hand-foot syndrome.Results: In 90.5 % of all patients, 5-FU toxicity was observed. With regard to MTHFR C677T mutation, 45.7 % heterozygote mutants and 19.0 % homozygote mutants were observed. MTHFR C677T polymorphism was statistically related to 5-FU toxicity (p = 0.000). In addition, MTHFR C677T mutation was closely related to hematopoietic toxicity (p = 0.005).Conclusion: MTHFR C677T can be used for the prediction of 5-FU toxicity, and can also predict hematopoietic toxicity in patients with colorectal cancer.
 Keywords: MTHFR genes, Polymorphism, Colorectal cancer, Biomarker, Toxicity

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.

Methylenetetrahydrofolate reductase polymorphism in healthy volunteers and its correlation with homocysteine levels in patients with thrombosis.

OBJECTIVE:To determine prevalence of methylenetetrahydrofolate reductase (MTHFR) mutations in apparently healthy individuals residing in Mumbai and patients with deep vein thrombosis (DVT) and coronary artery disease (CAD) and to correlate these polymorphisms with homocysteine (Hcy) levels.MATERIALS AND METHODS:This case–control study was initiated after receiving ethical approval and following the participant's written consent. One hundred and twenty unmatched healthy volunteers and 240 patients with arterial and venous thrombosis were enrolled. The prevalence of C677T and A1298C MTHFR mutations was detected using polymerase chain reaction-restriction fragment length polymorphism technique. Serum Hcy concentration and lipid levels were determined using biochemical kits.RESULTS:Allele frequency of 677T was 7%, 15%, and 14% in healthy controls, DVT, and CAD patients, respectively, while for 1298C allele, it was 31%, 33%, and 29%, respectively. The lipid markers in CAD patients were significantly low in comparison to the controls while the Hcy level in patients with thrombosis was higher in comparison with the controls. Highest Hcy levels were observed in participants with TT genotype followed by CT genotype and CC genotype in all the three groups. A higher risk of raised Hcy levels was seen in the variants (CT + TT) as compared to CC genotype in DVT (odds ratio [OR] = 3.39, 95% confidence interval [CI] = 1.39–8.2,P < 0.01) and CAD (OR = 21.67, 95%CI = 4.87–96.47,P < 0.0001). The risk observed for A1298C was 2.28 and 2.12 times higher in variants (AC + CC) of both DVT and CAD (OR = 2.28, 95%CI = 1.09–4.75 and OR = 2.12, 95%CI = 1.02–4.40, respectively).CONCLUSIONS:The prevalence of variants was more in thrombosis patients as compared to unmatched controls. Our study highlights the fact that MTHFR C677T polymorphism as compared to A1298C significantly affects Hcy levels in patients with thrombosis indicating that patients with mutant variants are at higher risk of rapid progression of their disease condition.

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.

Experience and Prognosis of Systemic Neonatal Thrombosis at a Level III NICU.

The objective of this article was to evaluate neonates diagnosed systemic thrombosis and their outcomes. We retrospectively evaluated data of neonatal systemic thrombosis between January 2011 and December 2016. Among 4376 hospitalized, 30 neonates (0.69%) were diagnosed systemic thrombosis. Their mean birth weight was 2422±1152 g (680 to 4750 g), gestational age was 35±5.4 weeks (25 to 41 wk). There were 25 neonates (83.3%) with venous, 5 patients (16.7%) with arterial thrombosis. The most common sites that thrombi localized were major vessels (n=11) and central nervous system (n=8). Central catheter insertion (76.7%) and prematurity (46.7%) were the most common risk factors. Congenital prothrombotic risk factors included G1691A mutation in factor V Leiden (n=1), mutation in factor XIII (n=1), C677T mutation in methylenetetrahydrofolate reductase (n=6). More than 1 congenital risk factor was identified in 5 patients. The patients were treated with low-molecular weight heparin. The mortality rate was 13.3% (n=4). Two patients required amputation (left foot, left upper extremity). Unilateral renal atrophy (n=1), cerebral palsy (n=2), hemiparesis (n=1) were identified among followed 24 patients. Critically ill neonates are at risk for thrombosis, and devastating consequences can result. As indwelling catheters and prematurity are important, careful monitorization, early diagnosis and therapy, cautious care of central catheter might reduce the incidence and adverse outcome.

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%).