Methylenetetrahydrofolate reductase (MTHFR) gene

Top PDF Methylenetetrahydrofolate reductase (MTHFR) gene:

A Study of C677T Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR) Gene and It’s Susceptibility in Coronary Artery Disease

A Study of C677T Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR) Gene and It’s Susceptibility in Coronary Artery Disease

DNA extracted from blood samples was checked for quality and quantity on 1% agarose gel. After checking for the purity of DNA, PCR was carried out in 20 μl reactions.PCR for the MTHFR gene gave a 198-bp fragment following enzymatic digestion of the PCR product using Hinf I restriction enzyme and incubated at 37°C for 24 h. Then it was electrophoresed in a 2% agarose gel at 90V for 30mins, and visualized in gel documentation. Three results were obtained for MTHFR 677, the PCR yielded a 198 bp product, which on digestion with Hinf I produced a 175 and 23 bp fragments for TT condition (homozygous polymorphic) and a 198,175 and 23 bp fragments for CT condition (heterozygous polymorphic) (Fig. 1). An undigested product length of 198 bp was retained by the wild types.
Show more

8 Read more

Are Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms C677T and A1298C Associated with Higher Risk of Pediatric Migraine in Boys and Girls?

Are Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms C677T and A1298C Associated with Higher Risk of Pediatric Migraine in Boys and Girls?

Migraine is a common neurological disorder that affects ~10% of the world’s population [1]; mainly women are affected [2]. Children with this disorder are also highly prevalent (3.5% - 5%) [3] and it is a major reason for absence from school, decreased academic level, higher rate of recurrent illnesses, etc. Migraine headache can also be associated with other symptoms such as nausea, vomiting, photo- and phonophobia [4]. This disorder is classified in two subtypes: migraine with aura (MA) and without aura (MO) [5]. MA comprises nearly 25% of all migraine cases in overall migraine population [6]. It is described by a disturbance of motor and visual activi- ties that lasts 20 to 30 minutes before the migraine attack [7]. MO makes up ~70% of all migraine cases [6] and its clinical features differ between adults and children [8]. Migraine, particularly MA, is associated with a higher risk of ischemic stroke (IS) in young women [9] [10]. Possible mechanisms predisposing migraine patients to IS may be vascular, neuronal or related to coagulation abnormalities and genetics [11]. Schurks et al. showed [12] that MA doubles the risk of ischaemic stroke, but MO—the most common type of migraine—is not a risk factor for stroke. With regard to genetic factors, previous studies provided evidence that the risk of ischaemic stroke in people with MA is further increased by a polymorphism in the MTHFR gene. Better phenotyping is a prerequi- site for a clearer understanding of these disorders [13]. The first epidemiological indication for migraine to be risk factor for ischemic stroke was described in 1975 by the Collaborative Group for the Study of Stroke in Young Women [14]. Since then several studies have also provided the same results [15] [16].
Show more

10 Read more

Methylenetetrahydrofolate Reductase (MTHFR) Gene Mutations in Patients with Idiopathic Scoliosis: A Clinical Chart Review

Methylenetetrahydrofolate Reductase (MTHFR) Gene Mutations in Patients with Idiopathic Scoliosis: A Clinical Chart Review

This study does not account for the downstream influences of MTHFR variants on neurotransmitter metabolism. For example, methylation is required to con- vert norepinephrine into epinephrine [22], and is also important in the negative feedback loop in serotonin metabolism [23]. Morningstar et al have previously described the role of these neurotransmitters in reflexive postural control [24], which is often altered in the majority of patients with IS [25]. However, it is likely that there are different gradations of downstream activity, possibly depen- dent upon the patient’s current lifestyle and dietary habits, and local environ- mental factors. Therefore, investigation into these aspects in this patient popula- tion is warranted.
Show more

7 Read more

Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms and Susceptibility to Childhood Acute Lymphoblastic Leukemia in an Iranian Population

Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms and Susceptibility to Childhood Acute Lymphoblastic Leukemia in an Iranian Population

The genotype and allelic frequencies of MTHFR gene polymorphisms in cases and controls are presented in Table 1. The results for rs1801131 (A1298C) variant showed that AC heterozygous genotype decreased the risk of ALL in comparison with AA homozygous genotype (OR=0.43, 95%CI=0.21-0.90, p=0.037). The minor allele frequency (C allele) was not associated with ALL (OR=1.36, 95%CI=0.93-1.98, p=0.12). Neither the overall Chi-square comparison of cases and control subjects (𝜒2=5.54, p=0.063) nor the logistic regression analysis indicated association between C677T polymorphism and ALL (OR=1.25, 95%CI=0.69-2.23, p=0.552; CT vs. CC).
Show more

8 Read more

Inherited Genetic Markers for Thrombophilia in Northeastern Iran (a Clinical-Based Report)

Inherited Genetic Markers for Thrombophilia in Northeastern Iran (a Clinical-Based Report)

Several studies have reported that factor V Leiden, which is responsible for more than 75% of inherited activated protein C resistance, is a common thrombotic risk factor affiliated with RPL (10-12).Other studies have reported an association between factor V and late pregnancy loss (13). Goodman CS et al. reportedan association between 4G/5G genotype of PAI-1 and recurrent pregnancy loss (14). The relationship of methylenetetrahydrofolate reductase (MTHFR) gene C677T, factor V (FV) gene G1691A and prothrombin (PT) gene G20210A polymorphisms to unexplained recurrent early spontaneous abortion were examined
Show more

6 Read more

Methylenetetrahydrofolate Reductase Gene Variant (MTHFR C677T) and Migraine: A Case Control Study and Meta-analysis

Methylenetetrahydrofolate Reductase Gene Variant (MTHFR C677T) and Migraine: A Case Control Study and Meta-analysis

significantly different than non-migraine headaches in their T allele and TT genotype distribution. This trend was also shown in previous studies in different popula- tions as described earlier. The results were not always consistent however and other studies reported negative findings. A relatively large study failed to show an asso- ciation between migraine and MTHFR C677T poly- morphism [17]. Such contradictions can be explained in part by methods of identification of migraine, the differ- ent populations (clinical, epidemiological samples), age and sex of the study participants, ethnic variations and geographic sites included in these studies. Studies have shown that there are genetic variations across different populations and geographic locations; these variations may have a significant role in genetic studies findings when different populations were included. A small Japa- nese study (n = 22) was the first to report a significant association between MTHFR C677T and MA [12] repli- cated by several other small studies (Korean n = 34 [36], Spanish n = 60 [37] and Italian n = 33 [38]) while large German (n = 656) and Finish (n = 898) studies failed to show significant association between MA and this poly- morphism [16,17]. These observations were in parallel
Show more

9 Read more

Association of parental methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in couples with unexplained recurrent pregnancy loss

Association of parental methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in couples with unexplained recurrent pregnancy loss

The MTHFR C677T gene of 198 bp was amplified by polymerase chain reaction (PCR) using oligonucleotide primer sequences forward 5 ′ -TGA AGG AGA AGG TGT CTG CGGGA-3 ′ and reverse 5 ′ -AGG ACG GTG CGG TGA GAG TG-3 ′ (Macrogen, Korea). The PCR was car- ried out on 25 μl reaction mixture of 12.5 μl master mix (Solis BioDyne, Estonia), 0.5 μl primers (10 pmol/μl), 3 µl of DNA was added while equal amount DNA of positive control and PCR grade water were added as negative con- trols then final volume of PCR-mix was adjusted by add- ing PCR grade water in above solution. The PCR tubes were placed on the tube holder of the thermo-cycler (Techne, UK). The cycle parameters for PCR initial dena- turation at 94 °C for 10 min followed by 35 amplification cycles of denaturation at 94  °C for 1  min; annealing at 60 °C for 1 min and extension at 72 °C for 1 min: followed by the final extension reaction at 72 °C for another 7 min.
Show more

5 Read more

<p>Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community</p>

<p>Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community</p>

Furthermore, admixture among different geographical populations might increase genetic variations and perhaps create new genotypic combinations within non-isolated (or non-native) populations. 45 Thus, genetic variations among some Middle Eastern individuals (e.g., Barbarians in North Africa, Kurdish, Upper Egyptian) 46–49 should be handled with caution, as increased consanguinity, reproductive iso- lation, and admixture with native source populations (e.g., Black Africans, South Eastern Asians, Caucasians) have considerable roles in gene fl ow and founder effects in these populations. For instance, the frequency of the Table 5 Haplotype Association of the MTHFR 677C>T Rs1801133 and MTHFR 1298A>C Rs1801131 SNPs with Response to Study Groups (Adjusted by Age)
Show more

13 Read more

Association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with primary glaucoma in Saudi population

Association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with primary glaucoma in Saudi population

Methods: We investigated MTHFR C677T genotypes and alleles frequencies in primary glaucoma [primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG)] patients and matched healthy controls in a case-control study. Two hundred ten primary glaucoma cases were studied for MTHFR C677T polymorphism and compared with 280 controls taken from the healthy population, employing the polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). The MTHFR gene was amplified using specific primers. The PCR products (294 bp) was subsequently digested with HinfI (New England Biolabs) at 37 °C for 12 h, separated by electrophoresis on 2 % agarose gels, and visualized with ethidium bromide staining. The restriction digestion yielded 168 and 126 bp fragments for TT, 294, 168 and 126 bp fragments for CT and undigested PCR product 294 bp indicating CC genotype.
Show more

8 Read more

Original Article Gene polymorphisms in the folate metabolic pathway and risk of pediatric acute lymphoblastic leukemia: a case-control study in a Chinese population

Original Article Gene polymorphisms in the folate metabolic pathway and risk of pediatric acute lymphoblastic leukemia: a case-control study in a Chinese population

Abstract: Polymorphisms in folate pathway genes may influence susceptibility to pediatric acute lymphoblastic leu- kemia (ALL). This case-control study was undertaken to analyze the association of genetic polymorphisms (677C>T and 1298A>C) of methylenetetrahydrofolate reductase (MTHFR) and reduced folate carrier (RFC1) (80G>A) with the risk of pediatric ALL in China. A total of 176 pediatric ALL patients and 170 matched healthy subjects (as con- trols) were included and DNA was extracted from the peripheral blood. SNaPshot single nucleotide polymorphism typing was used to determine the genotypes of MTHFR 677C>T, MTHFR 1298A>C, and RFC1 80G>A. All statistical analyses were conducted with SAS software (version 9.2; SAS Institute). There were no significant differences in the genotype and allele frequencies of MTHFR 677C>T, MTHFR 1298A>C, or RFC1 80G>A between patients and con- trols. No significant correlation was found between the combined genotypes of these polymorphisms and the risk of developing ALL in this study. Furthermore, no significant differences were observed for 677C>T and 1298A>C frequencies between the control and case groups. There was no association between MTHFR 677C>T, MTHFR 1298A>C, or RFC1 80G>A gene polymorphisms and risk of pediatric ALL in the Han Chinese population.
Show more

8 Read more

Folate, homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) 677C -> T variant, and the risk of myocardial infarction in young women: effect of female hormones on homocysteine levels

Folate, homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) 677C -> T variant, and the risk of myocardial infarction in young women: effect of female hormones on homocysteine levels

The most common enzyme defect associated with moderate hyperhomocysteinemia is a point mutation, C!T substitution at nucleotide 677 (677C!T), in the coding region of the gene for methylenetetrahydrofolate reductase (MTHFR), resulting in a thermolabile MTHFR variant with about 50% residual enzyme activity [1]. Among homogeneous populations positive asso- ciations were found between homozygous MTHFR genotype and cardiovascular disease [2±4], but the MTHFR 677TT mutation did not increase cardiovascular risk signi®cantly in the meta-analysis from BrattstroÈm [5]. Surprisingly, a negative association was found between the homozygous genotype and cardiovascular disease in postmenopausal women [6].
Show more

7 Read more

An analysis of Methylenetetrahydrofolate reductase and Glutathione S-transferase omega-1 genes as modifiers of the cerebral response to ischemia

An analysis of Methylenetetrahydrofolate reductase and Glutathione S-transferase omega-1 genes as modifiers of the cerebral response to ischemia

It has been established that cerebral ischemic injury results in a core of necrotic tissue surrounded by a penum- bra of tissue in which neurons are functionally inactive but still potentially viable [9]. The development of this ischemic penumbra is limited in time by a cascade of reac- tions in response to the initial ischemia followed by sub- sequent reperfusion. Reperfusion occurring shortly after ischemia reduces infarct volume, but at a later period may exacerbate ischemic injury [10]. It has been suggested that reperfusion increases reactive oxygen species (ROS) pro- duction which can have further deleterious consequences. Neuronal cell exposure to these ROS, which include nitric oxide, superoxide ions and hydroxyl radicals, can result in oxidative deoxyribonucleic acid (DNA) damage [11-14]. Methylenetetrahydrofolate reductase (MTHFR) and Glu- tathione S-transferase omega-1(GSTO-1) are two genes that are key participants in the metabolic pathways regu- lating oxidative stress in the brain (Fig 1). The C677T pol- ymorphism (NCBI SNP cluster ID rs# 1801133) in MTHFR gene results in an alanine-to-valine (A222V) sub- stitution which in turn causes a reduction in enzyme activ- ity and subsequent elevation of plasma homocysteine [15,16]. Hyperhomocysteinemia (HHcy) has been reported as an independent risk factor for stroke but may also influence ischemic stroke volume. A study of the cer- ebral volume and induced stroke following middle cere- bral artery occlusion in mice showed that HHcy was associated with increased oxidative damage and larger ischemic lesion [17-19]. The homocysteine (Hcy) dependent trans-sulfuration pathway is responsible for maintenance of the intracellular glutathione pool and reg- ulation of this pathway under oxidative stress (Fig 1). GSTO-1 is member of Phase II enzymes that catalyze glu- tathione-dependent antioxidant pathways (Fig 1). Fur- thermore GSTO-1 modulates rynodyne receptors thereby
Show more

5 Read more

Candidate genes for antidepressant response to selective serotonin reuptake inhibitors.

Candidate genes for antidepressant response to selective serotonin reuptake inhibitors.

glucocorticoid receptor; HPA, hypothalamic-pituitary-adrenal; MDD, major depressive disorder; MTHFR, methylenetetrahydrofolate reductase; MAP2, microtubule associated protein 2; MR, mineralocorticoid receptor; MAP, mitogen-activated protein; MEK, mitogen and extracellular signal- regulated protein kinase; MAOA, monoamine oxidase A; MAOB, monoamine oxidase B; MARCKS, myrisoylated alanine-rich C-kinase substrate; NMDA, N-methyl-D-aspartate; NR, NMDA receptor subunit; PDE, phosphodiesterase; PLC, phospholipase C; Pyk2, proline-rich tyrosine kinase 2; PKA, protein kinase A; PKA RIIb, PKA regulatory subunit IIb; PKC, protein kinase C; PP, protein phosphatase; RACK, receptor for activated PKC; RGS, regulator of G-protein signaling; SSRI, selective serotonin reuptake inhibitor; 5-HT, serotonin; SERT, serotonin transporter; SLC6A4, SERT gene; 5-HTTLPR, serotonin transporter linked polymorphic region; SNP, single nucleotide polymorphism; SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptor; trkB, troponin/receptor kinase B; TPH, tryptophan hydroxylase.
Show more

20 Read more

Genetic variation in folate metabolism is associated with the risk of conotruncal heart defects in a Chinese population

Genetic variation in folate metabolism is associated with the risk of conotruncal heart defects in a Chinese population

methylenetetrahydrofolate reductase (MTHFR), solute car- rier family 19, member 1 (SLC19A1), methionine synthase (MTR), and methionine synthase reductase (MTRR), have been proven to play crucial roles in this metabolic pathway. For example, the MTHFR gene, located on chromosome 1p36.3, encodes an enzyme that catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate [11], which is essential for folate-mediated one-carbon metabolism. SLC19A1 has also been referred to as reduced folate carrier-1 (RFC1), which is involved in the active transport of 5-methyltetrahydrofolate from the plasma to the cytosol and the regulation of intracellular concentra- tions of folate [12]. MTR catalyzes the remethylation of homocysteine to methionine [13], while MTRR catalyzes the regeneration of the cobalamin cofactor of MTR, thus maintaining MTR in an active state [14]. A single-nucleotide polymorphism (SNP) is a variation in a single nucleotide that is present to some appreciable degree within a population. Many studies have investigated associations between SNPs in the above-mentioned genes and the risk of CHD/CTD. Among them, the MTHFR C677T variant (TT), MTHFR A1298C variant (CC), SLC19A1 G80A variant (AG or AA), MTR A2576G variant (GG), and MTRR A66G variant (GG) have been extensively investigated. Although these gene vari- ants would theoretically influence the risk of CHD/CTD, studies have yielded conflicting results on this issue in differ- ent populations [10, 12, 15–19].
Show more

8 Read more

Association of Methylenetetrahydrofolate reductase (MTHFR 677C>T) polymorphisms with Ovarian Malignancy in women of Northern India

Association of Methylenetetrahydrofolate reductase (MTHFR 677C>T) polymorphisms with Ovarian Malignancy in women of Northern India

Ovarian cancer is considered to be the most common deadly gynecological cancer and is the fourth leading cause of women cancer, worldwide1.Like other malignancies, it is also a hereditary disease with multiple genetic events leading to the cancerous phenotype with high mortality. Importantly, the interaction between “Gene-Gene” and “Gene-Environmental” involved in the pathogenesis of this cancer and additionally, another factor such as family history, tobacco smoking, infertility and hormone replacement therapy2. Several studies have suggested that deficiency of nutrients, such as folate, vitamins, and microelements, has also been associated with increased risk for ovarian cancer2.
Show more

10 Read more

Frequency of APOE, MTHFR and ACE polymorphisms in the Zambian population

Frequency of APOE, MTHFR and ACE polymorphisms in the Zambian population

Background: Polymorphisms within the apolipoprotein-E (APOE), Methylenetetrahydrofolate reductase (MTHFR) and Angiotensin I-converting enzyme (ACE) genes has been associated with cardiovascular and cerebrovascular disorders, Alzheimer ’ s disease and other complex diseases in various populations. The aim of the study was to analyze the allelic and genotypic frequencies of APOE, MTHFR C677T and ACE I/D gene polymorphisms in the Zambian population. Results: The allele frequencies of APOE polymorphism in the Zambian populations were 13.8%, 59.5% and 26.7% for the ε 2, ε 3 and ε 4 alleles respectively. MTHFR C677T and ACE I/D allele frequencies were 8.6% and 13.8% for the T and D minor alleles respectively. The ε 2 ε 2 genotype and TT genotype were absent in the Zambian population. The genetic distances between Zambian and other African and non-African major populations revealed an independent variability of these polymorphisms.
Show more

10 Read more

Polymorphism in one-carbon metabolism pathway affects survival of gastric cancer patients: Large and comprehensive study

Polymorphism in one-carbon metabolism pathway affects survival of gastric cancer patients: Large and comprehensive study

Genetic factors play crucial roles in initiation of carcinogenesis and cancer development. Although gastric carcinogenesis undergoes highly complicated processes (e.g., abrogated gene expression, abnormal cell proliferation, resistance to apoptosis, dedifferentiation, enhanced survival, escape of immune surveillance, and metastasis) [4, 5], abrogation of gene expression or function caused by genetic changes (i.e., deletion, amplification and mutation) is the main force driving normal gastric cells into cancer cells. It has been shown that dysfunctions of one-carbon metabolism associated genes contribute to carcinogenesis via affecting DNA methylation, synthesis and repair [6]. One-carbon metabolism (OCM) pathway is a centered pathway involved in folate metabolism and DNA synthesis. It contains several crucial enzymatic reactions from folate uptake to synthesis of S-adenosylmethionine (SAM) [7]. Methylenetetrahydrofolate reductase (MTHFR) is a vitamin B2-dependent enzyme that carries out an irreversible conversion of 5,10-methylene-tetrahydrofolate (5,10-MTHF) to 5-methyl-tetrahydrofolate (5-MTHF) [8]. This is the rate-limiting step for OCM because 5,10- MTHF is the substrate for three other enzymatic reactions. Methionine synthase (MTR) catalyzes the remethylation of homocysteine to methionine [9], the residue critical for maintaining adequate intercellular folate level. Methionine synthase reductase (MTRR) maintains MTR in its active form. Thymidylate synthase (TS) catalyzes the reductive methylation of dUMP by 5,10-MTHF to form dTMP and dihydrofolate, a rate-limiting step in DNA synthesis [10]. TS is an essential enzyme in proliferating cells and is also an important target for a variety of chemotherapeutic drugs, e.g. 5-FU.
Show more

13 Read more

Lower Erythrocyte GST Activity in Autism Spectrum Disorder (ASD) Patients Compared to Normal Controls

Lower Erythrocyte GST Activity in Autism Spectrum Disorder (ASD) Patients Compared to Normal Controls

combination of genetic susceptibility via the reduced ability to remove metals including mercury or other neurotoxins from the system, and environmental exposure (35-37). Several genes have been reported associated with autism including genes involved in methionine transmethylation and transsulfuration pathways (8). Polymorphisms of Reduced Folate Carrier I (RFC1) gene, Methylenetetrahydrofolate Reductase (MTHFR), Transcobalamin II (TCN2), Catechol-O-methyltransferase (COMT) and Glutathione S-transferase mu 1 (GSTM1) have all been shown to be significantly increased among autistic children compared to controls (31, 38).
Show more

6 Read more

Haplotype analysis of the 5,10 methylenetetrahydrofolate reductase (MTHFR) c 1298A>C (E429A) polymorphism

Haplotype analysis of the 5,10 methylenetetrahydrofolate reductase (MTHFR) c 1298A>C (E429A) polymorphism

Our age estimation of the most recent common ances- tor of the studied alleles falls into a time period (30,000 to 40,000 years ago, the Aurignacian) which is typically associated with the spread of modern humans (Homo sapiens) in Europe [27,28]. The frequency of the MTHFR c.1298C allele is significantly higher in central Europe in comparison to African populations [3]. In addition, diet- ary folate intake can profoundly modify the effect of the C-allele on disease association, and the availability and intake of folate is different in Europe and Africa [29]. In summary, this could indicate an increased frequency of the C-allele due to changes in the (nutritional) environ- ment leading to selective advantages of the C-allele.
Show more

5 Read more

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies

It would be remiss to not briefly comment on the influ- ence of epigenetic factors on RA pathogenesis. It has become increasingly evident that the influence of epigenetic processes on the development of rheumatic diseases is probably as strong as the genetic background of a patient. The combina- tory nature of these processes forms a complex network of epigenetic modifications with the ability to regulate gene expression through activation or silencing of genes. Indeed, environmental triggers are involved in the development of RA as age, infections, smoking, nutrition, and pollution have been suggested to have an effect on the epigenetic background. Genome-wide analyses of the epigenome (eg, DNA meth- ylation, histone modifications) will enable the detection of additional genes involved in the pathogenesis of rheumatoid arthritis. In the future, knowledge of the epigenetic processes combined with enhanced genetic information will be essential for the understanding of the differences seen in the clinical picture of patients with rheumatic diseases such as RA.
Show more

17 Read more

Show all 10000 documents...