Methylenetetrahydrofolate Reductase C677T Mutation Research Articles

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.

Methylenetetrahydrofolate Reductase C677T and A1298C Mutations in Women with Recurrent Spontaneous Abortions in the Northwest of Iran

Introduction. Recurrent spontaneous abortion (RSA) is a significant obstetrical complication that may occur during pregnancy. Various studies in recent years have indicated that two common mutations (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene are risk factor for RSA. This study was carried out to determine the influence of (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene mutations with RSA. Materials and Methods. A total of 139 women were included in this study: 89 women with two or more consecutive miscarriages and 50 healthy controls. Total genomic DNA was isolated from blood leukocytes. To determine the frequency of the two common C677T and A1298C MTHFR gene mutations in the patients and controls, we used two methods, amplification refractory mutation system-PCR and PCR-restriction fragment length polymorphism. Results. There is no significant difference in the prevalence of 677T/T genotype among women with RSA and healthy controls (P = 0.285). Also no statistically significant difference in the frequency of A1298C MTHFR gene mutation was detected between the two groups (P = 0.175 ). Conclusion. In conclusion, the results indicate that the Amplification Refractory Mutation System-PCR method was in complete concordance with the results obtained by standard PCR-restriction fragment length polymorphism method. The results also show no significant difference in MTHFR C677T/A1298C genotype distribution among the two groups; therefore, further studies on larger population and other genetic variants to better understand the pathobiology of RSA are needed.

Methylenetetrahydrofolate reductase polymorphism in a case with atrial septal defect, deep venous thrombosis, thromboembolism and recurrent spontaneous abortion

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolism, where homocysteine converted to methionine. Methylenetetrahydrofolate reductase gene polymorphism is responsible for hyperhomocysteinemia resulting congenital heart defects, hypercoagulable states and recurrent abortion. A 30-yearold female was referred to our department with the diagnosis of atrial septal defect. In her medical history, she had two pregnancies with spontaneous abortus, deep venous thrombosis attacks, pulmonary thromboembolism and paradoxical cerebral embolus. The genetic workup revealed heterozygote MTHFR C677T mutation. We recommend suspecting MTHFR polymorphism in young fertile women with a history of spontaneous abortus or deep venous thrombosis or congenital heart disease with a paradoxical cerebral embolus.

Livedoid vasculopathy in a patient with lupus anticoagulant and MTHFR mutation: treatment with low-molecular-weight heparin

Livedoid vasculopathy is characterized by painful purpuric lesions on the extremities which frequently ulcerate and heal with atrophic scarring. For many years, livedoid vasculopathy has been considered to be a primary vasculitic process. However, there has been evidence considering livedoid vasculopathy as an occlusive vasculopathy due to a hypercoagulable state. We present the case of livedoid vasculopathy in a 21-year-old female who had been suffering of painful lower extremity lesions of 3years duration. The patient was found to be lupus anticoagulant positive and homozygous for methylenetetrahydrofolate reductase C677T mutation. The patient was successfully treated with low-molecular-weight heparin.

Folic acid supplementation increases survival and modulates high risk HPV-induced phenotypes in oral squamous cell carcinoma cells and correlates with p53 mRNA transcriptional down-regulation

BackgroundAlthough the primary risk factors for developing oral cancers are well understood, less is known about the relationship among the secondary factors that may modulate the progression of oral cancers, such as high-risk human papillomavirus (HPV) infection and folic acid (FA) supplementation. This study examined high-risk HPV and FA supplementation effects, both singly and in combination, to modulate the proliferative phenotypes of the oral cancer cell lines CAL27, SCC25 and SCC15.ResultsUsing a comprehensive series of integrated in vitro assays, distinct effects of HPV infection and FA supplementation were observed. Both high-risk HPV strains 16 and 18 induced robust growth-stimulating effects in CAL27 and normal HGF-1 cells, although strain-specific responses were observed in SCC25 and SCC15 cells. Differential effects were also observed with FA administration, which significantly altered the growth rate of the oral cancer cell lines CAL27, SCC15, and SCC25, but not HGF-1 cells. Unlike HPV, FA administration induced broad, general increases in cell viability among all cell lines that were associated with p53 mRNA transcriptional down-regulation. None of these cell lines were found to harbor the common C677T mutation in methylenetetrahydrofolate reductase (MTHFR), which can reduce FA availability and may increase oral cancer risk.ConclusionIncreased FA utilization and DNA hypermethylation are common features of oral cancers, and in these cell lines, specifically. The results of this study provide further evidence that FA antimetabolites, such as Fluorouracil (f5U or 5-FU) and Raltitrexed, may be alternative therapies for tumors resistant to other therapies. Moreover, since the incidence of oral HPV infection has been increasing, and can influence oral cancer growth, the relationship between FA bioavailability and concomitant HPV infection must be elucidated. This study is among the first pre-clinical studies to evaluate FA- and HPV-induced effects in oral cancers, both separately and in combination, which provides additional rationale for clinical screening of HPV infection prior to treatment.

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.

Distribution of prothrombin G20210A, factor V Leiden, and MTHFR C677T mutations in the middle Black Sea area (Tokat) of Turkey

To determine the distribution frequencies of prothrombin (factor II) G20210A, factor V Leiden, and methylenetetrahydrofolate reductase (MTHFR) C677T mutations in Tokat Province and the middle Black Sea area of Turkey. Materials and methods: The study group consisted of 243 patients who presented to our center with thrombosis and other complaints. Written permission from patients was obtained. DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the real-time polymerase chain reaction (RT-PCR) method. The data were subjected to statistical analyses. Results: According to the results of the study, factor V Leiden was detected in 37 patients, prothrombin G20210A was detected in 5 patients, and MTHFR C677T was detected in 146 patients. On the other hand, 79 patients carried none of these mutations. Conclusion: Factor V Leiden mutation was detected at a rate of 15.2%, which is much higher than the average in Turkey. The G20210A mutation rate in the prothrombin gene was determined as 2.1%. The MTHFR C677T mutation incidence was quite high (60%). The homozygous mutation rate was higher in diagnoses involving thrombosis, while the heterozygous mutation rate was higher in other diagnoses.

Anesthetic management in a patient with C677T Methylenetetrahydrofolate Reductase Mutation

Anesthetic management in a patient with C677T Methylenetetrahydrofolate Reductase Mutation

Hereditary Thrombophilia, Anti‐Beta2 Glycoprotein 1 IgM, and Anti‐Annexin V Antibodies in Recurrent Pregnancy Loss

We investigated the beta2-glycoprotein I and anti-annexin V antibodies as anti-phospholipid-cofactor antibodies; and factor V G1691A Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T mutations as hereditary thrombophilia in recurrent pregnancy losses (RPL). Study group consisted of 84 women with recurrent pregnancy loss and control group consisted of 84 women having at least one live birth. Methylenetetrahydrofolate reductase C677T homozygous mutation was detected in 28.5% of the study group and in 14.2% of the controls, and the difference was highly significant (P < 0.001). Heterozygous mutation of this gene was found in 64.3% of the study population and in 38.1% of the controls, and difference in heterozygous mutation frequency was also significant (P < 0.001). Both homozygous and heterozygous mutations of PT G20210A and factor V G1691A were not different between the groups. There was no significant difference in anti-annexin V levels and anti-beta2-gp 1 levels of the groups. We concluded that both homozygous and heterozygous mutations of MTHFR C677T were related with RPL in Caucasian women.

Ischemic Stroke in Young Patients with Cardiac Abnormalities and Hypercoagulable State: 2 Case Reports and Literature Review to Assess Diagnostic and Prevention Options

Abstract 4663 BackgroundStroke is the third leading cause of death and the leading cause of severe, long-term disability in the United States. The incidence of cerebrovascular accident (CVA) in young adults has been increasing. Since the etiology of CVA in young adults is more heterogeneous, making a diagnosis is often a challenge requiring extensive clinical investigation. We report 2 cases of ischemic stoke in young adults with multiple risk factors. Case ReportNo. 1. A 46-year-old male presented to the ER with loss of consciousness. Past medical history was unremarkable. MRA confirmed occlusion of the left posterior cerebral artery. Transesophageal Echocardiogram (TEE) revealed a patent foramen ovale (PFO) and atrial septal aneurysm (ASA). Hypercoagulable evaluation confirmed increased IgM anticardiolipin antibody, a lupus anticoagulant, and heterozygous MTHFR (Methylenetetrahydrofolate reductase) C677T mutation. Anticoagulation therapy was started with Heparin and then switched to Coumadin. Aspirin was also initiated along with folic acid, Vitamin B6 and B12, and smoking cessation therapy. Unfortunately, the patient developed hemiparesis and dementia after stroke.No. 2. A 50-year-old female presented to the ER with headache and blurred vision for one hour. Patient had cerebrovascular accident (CVA) 7 years prior to that event. She has been taking aspirin. MRI confirmed encephalomalacia in the left cerebellar hemisphere. TEE revealed a PFO. During the PFO closure procedure, an atrioseptal defect and a myxomatous were diagnosed. Patient was directed to use clopidogrel for at least six months after procedure, and aspirin indefinitely. DiscussionThe differential diagnosis for potential etiology in young people (under 55 years of age) of CVA is broader than that for older adults. Ischemic strokes are much more common than hemorrhagic in this group of patients. The atypical causes are more prevalent in the younger population, including cardiogenic cerebral embolus, hypercoagulable states, and autoimmune disease needs to be considered. Cardiogenic cerebral embolus is the most common cause of stroke in young adults. Stroke can be associated with abnormalities of the atrial septum, specifically PFO, atrial septal defect (ASD), aneurysm, and cardiac myxomas. Studies show that the prevalence of PFO in patients who have stroke of unknown cause (cryptogenic stroke) may be about 40 percent. More specifically, PFO increases the rate of paradoxical thromboembolic stroke that occurs by allowing blood clots from the venous system to enter the arterial system. This is particularly true in patients who have had a stroke at an age less than 55 years. PFO closure procedures may help to identify underlying causes of CVA, as was discussed in case 2. Some studies have described an association between atrial septal aneurysm (ASA) and embolic strokes. The embolus might originate in an ASA or from a clot around the edges of a PFO. The mechanism of cerebrovascular events with ASA may be platelet/thrombus formation at the site of the aneurysm. Aspirin may be effective therapy for preventing CVA. Emboli from cardiac myxomas also can lead to cerebral ischemia, infarction, and aneurysm formation. Up to half of cardiac myxomas produce systemic emboli. Consequently, studies show that inherited thrombophilic disorders in the pathogenesis of stroke might relate to congenital heart diseases. The data suggests that Factor V Leiden G1691A mutation or Prothrombin G20210A variant may be associated with PFO. An increased prevalence of right-to-left shunts in patients with cerebrovascular accident CVA and activated protein C resistance has also been documented. Antiphospholipid Antibody Syndromes (APS) are recognized as independent risks for Cerebrovascular Accident (CVA). APS are associated with a heterogeneous group of disorders that result in hypercoagulable states involving arterial and venous thrombosis. Cerebral circulation is particularly affected in APS. ConclusionBased on these observations, the authors conclude that hypercoagulable testing should be performed in young patients with CVA. In addition, PFO closure procedures may be an important diagnostic tool that helps to identify a subset of patients in whom the etiology of CVA was not apparent. Disclosures:No relevant conflicts of interest to declare.

Prevalence of Factor V Leiden G1691A, MTHFR C677T, and Prothrombin G20210A Among Asian Indian Sickle Cell Patients

The prevalence of factor V (FV) Leiden G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T mutations were investigated among 90 sickle trait, 61 sickle homozygous, 75 sickle beta thalassemia, and 15 HbSD Asian Indian sickle cell patients. In all, 297 healthy controls were evaluated to compare the polymorphism frequency. The prevalence of FV Leiden heterozygous G>A were significant in the group (P = .02), while PRT G20210A polymorphism was not seen among patients as well as controls. However, an increased frequency of the MTHFR 677 C>T genotype was seen among patients as well as controls, but this was not statistically significant (P = .13). This suggested a low impact of inherited hypercoagulability risk factors in the pathogenesis of sickle cell disease and/or its complications.

Methylene Tetrahydrofolate Reductase Gene Polymorphism and the Risk of Ischemic Stroke in Type 2 Diabetic Egyptian Patients

Background: A common C677T mutation of methylenetetrahydrofolate reductase (MTHFR) gene is reported to be associated with hyperhomocysteinemia a risk for atherosclerotic vascular diseases and ischemic stroke (IS). Aim: To clarify the possible role of the MTHFR 677C>T polymorphism in predisposition to IS and to assess the relationship of allelic variants of MTHFR gene with homocysteine (Hcy) plasma levels and other risk factors of atherosclerosis and IS in type 2 diabetic Egyptians. Subjects: Group I: 40 healthy non diabetic volunteers. Group II: 40 patients with type 2 diabetes mellitus (DM) without IS. Group III: 40 patients with type 2 DM and IS. Methods: Fasting blood samples were collected for research investigations. HPLC technique was used to estimate plasma Hcy levels. Polymerase chain reaction (PCR) assay with restriction fragment length polymorphism (RFLP) were used to examine the MTHFR polymorphism. Results: The frequencies of T allele and TT genotype were significantly higher in group III patients when compared to group I and group II (P T polymorphism is associated with elevated Hcy and uric acid plasma levels which increases the atherogenic risk and the prevalence of IS in type 2 diabetic Egyptian patients.

Inherited Thrombophilia in Childhood Arterial Stroke: Data from Lebanon

Pediatric ischemic stroke still represents a burden, and more than half of the survivors will experience cognitive or motor disabilities. The objective of this study was to investigate the role of thrombophilia in a cohort of children with arterial ischemic stroke. The records of infants and children with clinically and radiologically confirmed stroke were reviewed. Patients with venous or perinatal stroke were not included. Thirty-three patients were diagnosed with arterial ischemic stroke. The male/female ratio was 1.75:1. The median age was 4 years. The most frequent clinical manifestations were hemiparesis (54.5%) and seizures (33.3%). Genetic thrombophilia testing was available on 24 patients. Nine of the 24 patients (37.5%) were heterozygous for factor V Leiden. None of the patients carried the factor II G20210A variant. Ten patients (41.7%) were heterozygous and 3 (12.5%) were homozygous for methylenetetrahydrofolate reductase (MTHFR) C677T variant. Fifteen patients (62.5%) had one or more genetic polymorphism. Factor V Leiden was significantly associated with arterial ischemic stroke (P < 0.001). Stroke recurred in 2 children with multiple risk factors and MTHFR C677T mutation. Factor V Leiden is one of the major genetic risk factors for pediatric arterial ischemic stroke in Lebanon. MTHFR C677T was prevalent among patients with recurrent stroke.

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.

Detection of C677T mutation of MTHFR in subject with coronary heart disease by hairpin probe with enzymatic color on microarray

Molecular beacon (MB) is especially suited for detection of single nucleotide polymorphism (SNP), and the type of MB immobilized on the surface of microarray in particular, may detect multi-sample and multi-locus. However, the majority of MB needs to be labeled with fluorescence and quenching molecules on the two ends of the probe, and observed the reaction of fluorescence or complicated electrochemical signal produced hybridization of MB and target sequence by complex and expensive instruments. The “molecular beacon” and microarray designed appropriately in our study can produce visible light response signal induced by amplification effect of enzymatic color, and are avoided with the marker of fluorescence and quenching molecules and expensive instruments. The “molecular beacon” without fluorescence and quenching molecules is entitled as “hairpin DNA probe” by us for only the “hairpin” structure of traditional molecular beacon is adopted. The merits of two techniques, molecular beacon and amplification effect of enzymatic color, are successfully combined, and the technique is simple, sensitive and specific, to detect and compare the methylenetetrahydrofolate reductase (MTHFR) Gene C677T mutation of subjects between coronary heart disease (CHD) and control group. The results showed that MTHFR Gene C677T polymorphism is an independent risk factor for CHD.

Are inherited thrombotic risk factors associated with fibrostenosis in Crohnʼs disease?

Fibrostenotic lesions are common complications in Crohn's disease (CD) often requiring surgery. Inherited thrombotic risk factors are associated with fibrosis in other chronic inflammatory diseases. The aim of the study was to assess whether inherited thrombotic risk factors are associated with fibrostenosis in CD. Clinical data on 529 CD patients were collected retrospectively. Subjects were tested for and grouped according to the presence of factor V Leiden (FVL), the prothrombin G20210A, and the methylenetetrahydrofolate reductase C677T mutation (MTHFR). Patients who underwent CD-related intestinal surgery were assessed for the presence of fibrostenosis, which was the primary endpoint. The diagnosis of fibrostenosis was based on surgical, pathological, and histopathological reports. A Cox proportional hazards model was used for statistical analysis. Thirty-two (6.1%, heterozygous 30, homozygous 2) patients were carriers of FVL, 19 (3.6%, all heterozygous) carried the prothrombin variant, and 318 (60.1%) the MTHFR variant (243 heterozygous, 75 homozygous). In all, 303 (57.3%) patients underwent intestinal surgery. Fibrostenosis was identified in 219 (72.3%) surgical specimens. The rate of first intestinal surgeries with fibrostenosis tended to be more frequent in patients with the homozygous 677TT MTHFR mutation (hazard ratio, HR 1.39; 95% confidence interval [CI]: 0.98-1.97; P = 0.067). After adjustment for potential confounders homozygous 677TT MTHFR mutation did not remain a risk factor for intestinal surgery with fibrostenosis (HR 1.23; 95% CI: 0.77-1.98; P = 0.387). FVL and the prothrombin variant had no influence on the primary endpoint. The MTHFR 677TT mutation, factor V Leiden, and the prothrombin G20210A mutation are not associated with fibrostenosis in CD.

Role of Thrombophilia in Vascular Access Thrombosis Among Chronic Hemodialysis Patients in Tunisia

Vascular access thrombosis represents a serious and common problem in hemodialysis patients. Therefore, identification of relevant thrombotic risk factors could lead to an improved antithrombotic therapy. This case control study was performed to evaluate the relationship between some thrombophilias and vascular access thrombosis in hemodialysis patients. Seventy-eight patients undergoing dialysis (between May 2007 and September 2009) were selected as subjects. This sample was divided into two groups; a case group of 28 patients who had sustained one or more thrombotic events that resulted in vascular access failure and a control group of 50 patients, who had never had a thrombotic occlusion of a functioning permanent dialysis access. Antithrombin, protein C and protein S levels were measured. Also, both groups were tested for the factor V Leiden mutation, the prothrombin G20210A mutation, the methylene tetrahydrofolate reductase C677T and A1298C mutations. Among genetic mutations of factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase genes, the C677T methylene tetrahydrofolate reductase mutation was the only significant genetic cause of vascular access thrombosis (P=0.005). Our data demonstrated a significantly increased risk of vascular access thrombosis in carriers of the C677T methylene tetrahydrofolate reductase mutation.

Hyperhomocysteinemia and the methylene tetrahydrofolate reductase C677T mutation in splanchnic vein thrombosis

The role that hyperhomocysteinemia (HH) and the C677T mutation in 5,10-methylenetetrahydrofolate reductase (MTHFR) play in splanchnic vein thrombosis (SVT) remains unclear due to this unusual thrombotic location. To analyse the possible association of HH with the C677T mutation in the MTHFR gene in SVT. We determined homocysteine levels and the C677T MTHFR mutation, along with classical cardiovascular risk factors, in 48 patients with SVT (18 Budd-Chiari syndrome, 11 mesenteric vein thrombosis, 19 portal vein thrombosis) and 84 controls. In the univariate analysis, patients with SVT showed statistically higher homocysteine levels (P =0.044). After adjusting for total cholesterol, differences disappeared (P =0.256). However, no differences in homocysteine levels were observed when comparing the three SVT types (P =0.199), even after adjusting for age and total cholesterol (P =0.095). In addition, the prevalence of the TT genotype was no different when controls were compared with patients with SVT (P =0.253) or with SVT subtypes (P =0.885). No association was found between HH (>15 μm) and the TT genotype in cases (P =0.404), controls (P =0.178), or in the different SVT subtypes (P =0.495). Our results suggest that HH and the homozygous genotype in the MTHFR C677T mutation do not seem to play a role in SVT development.

Association of Methylene Tetrahydrofolate Reductase C677T Genotype With Type 2 Diabetes Mellitus Patients With and Without Renal Complications

Diabetes is gradually getting the status of a global epidemic, with India projected as the capital of type 2 diabetes mellitus (T2DM). Nephropathy is an important complication of diabetes and a major cause of end-stage renal disease. Studies from different parts of the world have given controversial results regarding the association of methylene tetrahydrofolate reductase (MTHFR) gene variation with T2DM and diabetic nephropathy (DN). This case-control study assessed the association of MTHFR C677T mutation in T2DM and DN cases. Genotyping of MTHFR was carried out for 236 T2DM cases with diabetes diagnosed for >8 years, having either normoalbuminuria (n=100) or established DN (n=136). One hundred age- and sex-matched healthy individuals with normal blood sugars and no family history of T2DM were selected as controls. This first report from India gives a highly significant odds ratio of 4.0423 (95% confidence interval=1.8753-8.7133), indicating that the MTHFR 677T allele confers a fourfold risk of developing DM in our population. The frequency of the T allele in both the DM and DN groups was similar (i.e., 0.16 and 0.11, respectively), showing no association with the initiation or progression of DN. Individuals with a family history of diabetes or with risk factors such as obesity, hypertension, and impaired glucose tolerance should be screened for MTHFR C677T mutation and may be prescribed folic acid, vitamin B6, and vitamin B12 to assess if this helps in delaying the onset of diabetes.

The association between inherited thrombophilias and pregnancy-related hypertension recurrence

The aim of this study was to determine the association between inherited thrombophilias and pregnancy-related hypertension recurrence. In this case-control study, blood samples were obtained from patients who had at least two pregnancies complicated with pregnancy-related hypertension (n = 41) and healthy, normotensive pregnancies delivered without any complication (n = 38). Following the DNA extraction, samples were tested for factor V Leiden, prothrombin G20210A and homozygous methylene tetrahydrofolate reductase (MTHFR) C677T mutations using reverse hybridization method. Common inherited thrombophilias were present in 26.8% of women with recurrent pregnancy-related hypertension group and 23.7% of control subjects (odds ratio 1.1; 95% confidence interval, 0.6-1.9). No significant difference was observed between two groups in terms of factor V Leiden, prothrombin G20210A and MTHFR C677T mutations. Our data suggest that factor V Leiden, prothrombin G20210A and MTHFR C677T mutations are not associated with pregnancy-related hypertension recurrence.