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Objective. To study the association of the C677T polymorphism of the MTHFR gene with the risk of developing schizophrenia in a large cohort including patients with schizophrenia and mentally healthy people and to investigate the association of this polymorphism with the severity of schizophrenia symptoms and the simultaneous effects of genetic variants and environmental factors on these symptoms. Materials and methods. The genotyping cohort consisted of 1357 schizophrenia patients and 711 controls. Symptom severity was evaluated on the PANSS. Environmental factors were birth complications and history of traumatic brain injury. Results and conclusions. No association was found between the C677T polymorphism of the MTHFR gene and schizophrenia. There was no genotype effect on symptom severity on PANSS subscales. The interaction between the polymorphism of interest and environmental factors had no effect on the severity of schizophrenia symptoms. These results do not support data from a number of investigations of an association between the C677T polymorphism of the MTHF gene and schizophrenia

BackgroundThe methylenetetrahydrofolate reductase (MTHFR) rs1801131 A/C variant results in a decrease in MTHFR enzymatic activity, which may play an important role in folate metabolism and is also an important source of DNA methylation and DNA synthesis. Several case-control studies have been conducted to assess the association of MTHFR rs1801131 polymorphism with the risk of urinary cancers, yet with conflicting conclusions. To derive a more precise estimation of above relationship, the association between the MTHFR rs1801131 A/C polymorphism and the risk of urinary cancer was performed.MethodsA total of 28 case-control studies was identified. The odds ratios (OR) with 95% confidence intervals (CI) was calculated to assess.ResultsOn one hand, we found that the MTHFR rs1801131 A/C polymorphism was associated with increased whole urinary cancers’ risk (for example CA vs. AA: OR = 1.12. 95%CI = 1.01–1.24). On the other hand, we found that the MTHFR rs1801131 A/C polymorphism might increase bladder cancer risk both in Asian (C-allele vs. A-allele: OR = 1.35. 95%CI = 1.15–1.60) and African populations (CA vs. AA: OR = 1.63. 95%CI = 1.17–2.25).ConclusionsOur current analysis suggested that MTHFR rs1801131 A/C is associated with urinary cancers, especially bladder cancer.

The aim of our study was to investigate the effect of maternal and embryo MTHFR C677T and A1298C polymorphisms on embryo aneuploidies and mosaicism and the correlation between these genetic variant...

Background Essential hypertension (EH) is common and multifactorial disorders likely to be influenced by multiple genes. The methylenetetrahydrofolate reductase (MTHFR) gene rs1801133 polymorphism is related to MTHFR enzyme activity and to plasma homocysteine concentration. In addition, variations in MTHFR functions likely play roles in the etiology of EH. So far, larger number of studies between MTHFR rs1801133 polymorphism and EH have provided controversial or inconclusive results. To better assess the purported relationship, we performed a comprehensive analysis of 50 publications. Methods Eligible studies were identified by searching the PubMed, Wanfang and CNKI databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess this association. Results Overall, increased significant associations were detected between MTHFR rs1801133 polymorphism and EH risk (such as T vs. C: OR = 1.37, 95%CI = 1.24–1.52, P = 0.000), the same as in race subgroup (Asian: T vs. C: OR = 1.46, 95%CI = 1.29–1.67, P = 0.000; China: T vs. C: OR = 1.51, 95%CI = 1.30–1.74, P = 0.000). Similar associations were also found in source of control and genotype methods subgroups. Conclusions Our study showed evidence that MTHFR rs1801133 null genotype may increase EH risk. Future studies with larger sample size are warranted to further evaluate this association in more detail.

Background: The relation between methylenetetrahydrofolate reductase)MTHFR( polymorphisms and the risk of developing Chronic lymphocytic leukemia (CLL) is not still clear, while there are reports about the association of MTHFR C677T and A1298C polymorphisms with developing CLL, there are other reports that rolled out the association of MTHFR polymorphisms with developing CLL. Therefore herein we carried out this meta-analysis to clear the association of MTHFR polymorphisms with the risk of CLL Methods: A comprehensive search was performed through PubMed, Scopus and Embase from inception to Aug 2020. Odds ratios (OR) with their corresponding 95% confidence intervals (CI) for five possible genetic models were calculated. Heterogeneity was evaluated using the Cochran Q test and the I2 statistic. Results: Totals of 1290 cases and 1887 controls for the C677T polymorphism and 1117 cases and 1256 controls for the A1298C polymorphism were included in our analysis. Analyzing the MTHFR C677T and A1298C polymorphisms genotypes showed an association between MTHFR polymorphism at A1298C under Allelic model and the risk of CLL (OR = 1.12, 95% CI = 1.01–1.25), however there was no association between MTHFR polymorphism at MTHFR C677T and risk of CLL. Conclusion: The risk of developing CLL might be associated with MTHFR polymorphism at A1298C under allelic model and not associated with MTHFR polymorphisms at C677T, However, further studies considering other factors such as age, gender, ethnicity, gene-gene interaction and environmental condition are needed to clear the true association of MTHFR polymorphisms with CLL.

Cerebral venous sinus thrombosis (CVST) as a severe neurological emergency, is represented by variable conditions in its clinic presentation, onset, risk factors, neuroimagistic features and outcome. The genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C was associated with CVST. We aimed to characterize the prevalence of MTHFR gene polymorphisms associated with cardiovascular risk factors in the group of patients with CVST. Also, we studied additional causes associated with CVST including local infections, general infections, obstetric causes (pregnancy, puerperium) and head injury. This is a retrospective study including 114 patients which referred to our hospital between February 2012&ndash, February 2020. The protocol included demographic (age, sex), clinical, neuroimagistic features, paraclinic (genetic polymorphism of MTHFR, factor V G1691A&mdash, Leiden, prothrombin G20210A, PAI-1 675 4G/5G, Homocysteine level, the lipid profile, blood glucose and Glycohemoglobin HbA1c, high- sensitive C- reactive protein- hsCRP) data, as well as treatment and outcome. The mean age was 37.55 years with a female predominance (65.79%). In the first group of patients with inherited thrombophilia (60 cases, 52.63%) we found genetic mutation includes MTHFR C677T (38.59%) and A1298C (14.03%), factor V G1691A- Leiden (15.78%), prothrombin G20210A (2.63%), PAI-1 675 4G/5G (42.98%), and hyperhomocysteinemia (35.08%). At the second group with other etiology of CVST, except thrombophilia, we included 54 patients (47.36%). The most common sites of thrombosis were the superior sagittal sinus (52.63%). Headache was the most common symptom (91.22%) and seizures were the main clinical presentation (54.38%). The MTHFR polymorphism was significantly correlated with higher total cholesterol (TC) (p = 0.023), low- density lipoprotein cholesterol (LDL) (p = 0.008), homocysteine level (tHcy) (p &lt, 0.001). Inside the first group with MTHFR polymorphism we have found a significant difference between the levels of homocysteine at the patients with MTHFR C677T versus MTHFR A1298C polymorphism (p &lt, 0.001). The high-sensitive C-reactive protein (hsCRP) was increased in both groups of patients, but the level was much higher in the second group (p = 0.046). Mortality rate was of 2.63%. Demographic, clinical and neuroimagistic presentation of CVST in our study was similar with other studies on the matter, with a high frequency of thrombophilia causes. MTHFR gene polymorphisms (C677T and A1298C) are increased in prevalence in CVST. PAI-1 675 4G/5G gene mutation seems to be involved in CVST etiology. Plasma C-reactive protein level and hyperhomocysteinemia should be considered as a prognostic factor in CVST.

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) in hormone metabolism pathways might cause metabolic disturbances and contribute to the development of polycystic ovary syndrome (PCOS) and ovarian cancer, but the published studies were inconsistent. The aim of the present study was to evaluate the MTHFR C677T (rs1801133) and A1298C (rs1801131) gene polymorphisms in the risk of PCOS and ovarian cancer by meta-analysis. A comprehensive electronic search was conducted in databases for studies published from 1995 to 2020. The pooled ORs were calculated by Revman 5.2 software. Twenty-nine articles including 45 case–control studies were included. We found that MTHFR C677T polymorphisms were correlated with elevated PCOS risk (TT vs. CT+CC: OR = 1.41, 95%CI = 1.20–1.67; TT+CT vs. CC: OR = 1.54, 95%CI = 1.07–2.22; CT vs. CC+TT: OR = 1.18, 95%CI 1.04–1.33; TT vs. CC: OR = 1.47, 95%CI = 1.03–2.11; T vs. C: OR = 1.25, 95%CI = 1.06–1.47), which were more obvious in Middle Eastern subgroup. MTHFR A1298C polymorphisms were also associated with overall PCOS susceptibility (CC vs. AC+AA: OR = 2.55, 95% CI = 1.61–4.03; CC+AC vs. AA: OR = 1.84, 95%CI = 1.04–3.28; CC vs. AA: OR = 2.66, 95%CI = 1.68–4.22; C vs. A: OR = 1.67, 95%CI = 1.03–2.71), which were mainly reflected in Asian subjects. For ovarian cancer, MTHFR C677T polymorphisms were only related with elevated ovarian cancer risk in Asian population, while no significant association was found for A1298C polymorphisms. This meta-analysis suggested that MTHFR C677T and MTHFR A1298C polymorphisms were correlated with elevated PCOS risk. MTHFR C667T only posed a higher risk for ovarian cancer in Asians instead of other populations, while MTHFR A1298C polymorphisms were not related to ovarian cancer risk. Further studies are needed to validate the conclusion.

We report a case of a 61-years-old woman in remission of psoriasis for 20 years. She presented recurrence of psoriasis in the form of plaques few days after taking L-methylfolate 15mg/day. The L-methylfolate was prescribed as an adjuvant for the treatment of depression in a patient with the methylenetetrahydrofolate reductase gene polymorphism (MTHFR).

Background: The use of molecular genetic technologies has made it possible to show that the genetic factor plays a significant role in the development of obesity. In addition, in obese people the supply with vitamins, in particular with folic acid, is largely controlled genetically.Aim: To study an association of the rs1801133 polymorphism of the MTHFR gene with folic acid deficiency in the residents of the Moscow region depending on their body mass index.Materials and methods: rs1801133 polymorphisms were identified in 326 subjects (74 male and 252 female) aged from 20 to 65 years, living in the Moscow region. The DNA was isolated from blood by the sorption on silica gel-coated magnetic particles. DNA was isolated with the use of the epMotion 5075 automatic station (Eppendorf, Germany). To identify the polymorphism, a polymerase chain reaction was used, followed by cleavage of the Hinf1 restriction endonuclease products, with analysis of these products by gel electrophoresis. The equipment CFX96 Real Time System (BIO-RAD, USA) was used. Folic acid was measured by ID-Vit® Folic Acid test system (R-Biopharm, Germany).Results: According to the results of folic acid measurements in blood, a deficiency of this vitamin was found in 24.2% of the studied residents of the Moscow region. Analysis of the genotyping results did not show any association of the rs1801133 MTHFR gene polymorphism with the serum levels of folic acid. However, in the subjects with overweight and obesity, there was a statistically significant association between the T allele of the rs1801133 of the MTHFR gene polymorphism and a low level of folic acid (odds ratio 2.5, 95% confidence interval 1.09–5.74, p = 0.03).Conclusion: The rs1801133 polymorphism of the MTHFR gene significantly contributes to the development of folic acid deficiency in overweight and obese individuals.

The article provides data on 114 patients with stage 2 primary arterial hypertension (AH) according to the WHO classification (2008) and the development of complications associated with hemostasis violations depending on the nationality of patients (Mordva-Moksha, Russians) and polymorphism methyltetrahydrofolate reductase (MTHFR) gene carrier state. Polymorphic genotypes were identified using polymerase chain reaction (PCR) along with traditional clinical and instrumental studies. The analysis of MTHFR gene polymorphic genotypes carriage showed a significant predominance of intermediate genotypes (88% – CT genotype at position 677, 66% – AC genotype at position 1298) regardless of nationality of patients with AH. The carriage of “unfavourable” TT genotypes of MTHFR gene at position 677 prevails in men of the Mordva-Moksha (20%) as compared with the patients of Russian nationality. During a 3-year follow-up, 12% of patients with AH (6.9% of MordvaMoksha and 5.1% of Russian) suffered acute myocardial infarction (MI) or acute cerebrovascular accident (ACVA). Cardiovascular complications (MI/ACVA) developed 1.5 times more often in Mordva patients than in patients with AH of Russian nationality. IM occurred 3 times more often in Mordva-Moksha men than in patients with AH of Russian nationality. The Mordva-Moksha men with AH, who were carriers of the “unfavourable” TT genotypes of MTHFR gene at position 677, developed a complication in the form of MI in 100% cases.

Myocardial infarction (MI) occupies one of the leading positions among the complications of the cardiovascular system. The process of atherothrombosis lies in the genesis of MI development. An important mechanism of thrombus development is the genetic determinancy of methylenetetrahydrofolate reductase (MTHFR) gene. The purpose of this work was to study of this gene genotypes carriage and to estimate its prognostic significance in the development of myocardial infarction in the indigenous population of the Republic of Mordovia, depending on nationality. 88 patients with Q MI (Russian patients n = 48, Mordvia-Moksha n = 40) and 100 healthy subjects (Russians n = 50 and Mordva-Moksha n = 50) have been examined. The average age of patients with Q MI was (58,8 ± 6,4) years. In patients with Q MI, the carriage of the TT genotype of the MTHFR gene has been detected in 41 % of cases, and in healthy individuals of this genotype it has not been revealed. In patients of Mordvian nationality (moksha), the carriage of the genotype TT of the MTHFR gene was more frequent (47,5 %) than in patient of Russian nationality (37,5 %), with OR for the Mordovian-Moksha patients equal to 11.40 (CI 1.38-94, 0) and for patients of Russian nationality with OR = 7,69 (CI 1.57-37.76). It reflects a more significant risk of carriage of the TT genotype in patients of Mordvian (moksha) nationality in terms of increased thrombus formation and MI development.

Background: We aim to determine the relationships among vitamin B12, folic acid, homocysteine (Hcy), and methylenetetrahydrofolatereductase (MTHFR) C677T polymorphism, as well as the clinical importance of these relationships, in patients using valproic acid (VPA), carbamazepine (CBZ), and levetiracetam (LEV) as monotherapy and polytherapy. Methods: We enrolled 37 patients on VPA, 30 on CBZ, 31 on LEV, 30 on multidrug therapy, and 60 control subjects. We compared the levels of vitamin B12, folic acid, Hcy and polymorphism. Results: Vitamin B12 was low in patients on CBZ (p=0.02) and in combined CBZ and VPA (p=0.02). B12 was low in combined CBZ and VPA (p=0.05). In patients without polymorphism, Hcy was high on VPA (p=0.02), and folic acid was the low on CBZ (0.005). In patients with polymorphism, vitamin B12 was low on CBZ (p=0.02), and folic acid was low on VPA (p=0.04). Vitamin B12 was low in combined CBZ and VPA (p=0.05). Conclusions: Vitamin B12 therapy is necessary on CBZ and on combined CBZ and VPA. VPA should not be used in the presence of other thrombophilic risk factors because of hyperhomocysteinemia. Polytherapy does not increase hyperhomocysteinemia risk in comparison to monotherapy. Vitamin B12, folic acid, Hcy do not effect on seizure frequency.

Background: The methylenetetrahydrofolate reductase gene (MTHFR) is one of the most investigated genes associated with breast cancer for its role in epigenetic pathways. Objectives: The objectives of this metaprediction study were to examine the polymorphism-mutation risk subtypes of MTHFR and air pollution as contributing factors for breast cancer. Methods: For triangulation purposes in metapredictive analyses, we used a recursive partition tree, nonlinear association curve fit, and heat maps for data visualization, in addition to the conventional comparison procedure and pooled analyses. Results: We included 36,683 breast cancer cases and 40,689 controls across 82 studies for MTHFR 677 and 23,252 cases and 27,094 controls across 50 studies for MTHFR 1298. MTHFR 677 TT was a risk genotype for breast cancer (p = .0004) and in the East Asian subgroup (p = .005). On global maps, the most polymorphism-mutations on MTHFR 677 TT were found in the Middle East, Europe, Asia, and the Americas, whereas the most mutations on MTHFR 1298 CC were located in Europe and the Middle East for the control group. The geographic information system maps further revealed that MTHFR 677 TT mutations yielded a higher risk of breast cancer for Australia, East Asia, the Middle East, South Europe, Morocco, and the Americas and that MTHFR 1298 CC mutations yielded a higher risk in Asia, the Middle East, South Europe, and South America. Metapredictive analysis revealed that air pollution level was significantly associated with MTHFR 677 TT polymorphism-mutation genotype. Discussion: We present the most comprehensive analyses to date of MTHFR polymorphism-mutations and breast cancer risk. Future nursing studies are needed to investigate the health impact on breast cancer of epigenetics and air pollution across populations.

Aim: To assess the risk for trisomy 21 in children, depending on the polymorphisms C677T and A1298C of the methylenetetrahydrofolate reductase (MTHFR) gene in mothers. Methods: For 93 mothers who have children with trisomy 21 and 202 mothers of healthy children (control group), genotyping of MTHFR polymorphisms C677T and A1298C was performed. Results: For each polymorphism, three genotypes were identified (normal homozygous, heterozygous and mutant homozygous). For the polymorphism C677T, the frequencies of the three genotypes (CC, CT and TT) were 50.5%, 40.8% and 8.6% in mothers of children with trisomy 21, versus 42.6%, 46% and 11.4% in mothers of healthy children, with no statistically significant differences. The frequency of the polymorphism A1298C was not statistically significant between the two groups for the genotype (AA) (48.4% vs 56.4%) or the genotype (AC) (39.8% vs 38.6%), but the genotype TT was more frequent in mothers of children with trisomy 21 (11.8% vs 4.9%; p = 0.033; OR = 2.57). Conclusion: Women with genotype CC for the polymorphism A1298C of the MTHFR gene have a 2.57 times higher risk of offspring with trisomy 21.

Objective: This case control study examined the frequency and distribution of the C677T and A1298C single-nucleotide polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene in Turkish patients with chronic periodontitis. Materials and Methods: This study included 89 subjects: 49 patients with chronic periodontitis and 40 healthy persons. Medical and periodontal histories were taken, and PD, CAL, PI, and BOP were recorded as the clinical parameters. The blood samples were taken from the subjects, and their DNA was obtained. The MTHFR gene's single nucleotide polymorphisms 677C→T and 1298A→C genotyping were analyzed using the RFLP assay, then PCR. Results: There was a significant difference between the groups except for age when the clinical findings. Single-nucleotide polymorphisms in the MTHFR gene C677T and 1298C regions were not found to be significantly different between the groups. Conclusion: The study revealed no association between the MTHFR polymorphism and the risk of chronic periodontitis; however, increasing the number of patients is useful when performing further studies. This present study is important because it is, to the best of our knowledge, the first study to research the interrelation between the MTHFR gene and chronic periodontitis.

The methylenetetrahydrofolate reductase ( MTHFR) gene is one of the most investigated of the genes associated with chronic human diseases because of its associations with hyperhomocysteinemia and toxicity. It has been proposed as a prototype gene for the prevention of colorectal cancer (CRC). The major objectives of this meta-analysis were to examine the polymorphism-mutation patterns of MTHFR and their associations with risk for CRC as well as potential contributing factors for mutations and disease risks. This analysis included 33,626 CRC cases and 48,688 controls across 92 studies for MTHFR 677 and 16,367 cases and 24,874 controls across 54 studies for MTHFR 1298, comprising data for various racial and ethnic groups, both genders, and multiple cancer sites. MTHFR 677 homozygous TT genotype was protective ( p < .05) for CRC for all included populations; however, with heterogeneity across various racial–ethnic groups and opposing findings, it was a risk genotype for the subgroup of Hispanics ( p < .01). Additional countries for which subgroup analyses resulted in 677 TT as a risk genotype included Turkey, Romania, Croatia, Hungary, Portugal, Mexico, Brazil, U.S. Hawai’i, Taiwan, India, and Egypt. Countries with the highest mutation rates and risks for both MTHFR 677 and 1298 genotypes are presented using global maps to visualize the grouping patterns. Meta-predictive analyses revealed that air pollution levels were associated with gene polymorphisms for both genotypes. Future nursing research should be conducted to develop proactive measures to protect populations in cities where air pollution causes more deaths.

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Background Methylenetetrahydrofolate Reductase (MTHFR) polymorphisms by impairing folate metabolism may influence the development of allergic diseases. The results of studies evaluating the relationship between MTHFR polymorphisms and atopic disease are controversial. The aim of this study was to investigate the association between the polymorphisms of C677T and A1298C for MTHFR gene and allergic rhinitis (AR) in children. Methods Ninety patients followed up with diagnosis of allergic rhinitis in our clinic and 30 children with no allergic diseases were included in the study. All participants were genotyped for the MTHFR (C677T) and (A1298C) polymorphisms. Vitamin b12, folate and homocysteine levels were measured. Results The mean age of patients was 9.2 ± 2.9 years; 66.7% of the patients were male. There was no significant difference between patient and control groups regarding gender, age and atopy history of the family (p > 0.05). The frequency of homozygotes for MTHFR C677T polymorphism in the patient and control groups was 3.3% and 10%, respectively. The frequency of homozygotes for MTHFR A1298C polymorphism among groups was 26.7% and 16.7%, respectively. The association between allergic rhinitis and polymorphisms of C677T and A1298C for MTHFR gene was not statistically significant in patients compared with controls (p > 0.05). There were no statistically significant differences between the patients and the control group in terms of serum vitamin b12, folate and homocysteine levels (p > 0.05). Conclusion We found no evidence for an association between allergic rhinitis and polymorphisms of C677T and A1298C for MTHFR gene in children. Further studies investigating the relationship between MTHFR polymorphism and AR are required.

[No abstract available]

Objectives: The association between methylenetetrahydrofolate reductase gene polymorphisms and unexplained recurrent miscarriage is elusive. The recommendations for improving pregnancy outcomes in these patients keep changing based on the available evidence. The aim of this study is to analyze the impact of low molecular weight heparin on obstetric outcomes of recurrent miscarriage patients complicated with methylenetetrahydrofolate reductase gene polymorphism. Material and methods: We reviewed medical records of 121 patients with a history of recurrent miscarriage complicated by methylenetetrahydrofolate reductase gene polymorphisms, retrospectively. From among them, 68 patients were treated only with folic acid and iron. The remaining 53 patients were treated with folic acid, iron and prophylactic doses of low molecular weight heparin. The subsequent pregnancy outcomes of these patients were noted. Results: The live birth rate was higher in patients with anticoagulant therapy than in patients without anticoagulant therapy (48.5% vs. 69.8%, respectively, p: 0.015) and the congenital anomaly rate was lower in anticoagulant therapy group (17.6% vs. 3.8%, respectively, p: 0.022). The other obstetric outcomes were found to be similar between the two groups. Conclusions: The current study demonstrated that low molecular weight heparin improved the live birth rates among unex­plained recurrent miscarriage patients complicated with methylenetetrahydrofolate reductase gene polymorphisms. How­ever, the routine use of low molecular weight heparin did not improve the late pregnancy complications in these selected patients in the eastern region of our country. Further studies are needed to discriminate the effect of anticoagulation on the live birth rate of each of methylenetetrahydrofolate reductase gene polymorphism type.

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been extensively explored, but their results are conflicting rather than conclusive. To derive a more precise estimation, we carried out not only an updated meta-analysis but also a combined analysis based on all the available studies estimating the association between MTHFR C677T and/or A1298C and breast cancer risk. With respect to C677T polymorphism, the results suggested that 677T allele was associated with significantly elevated breast cancer risk in overall analysis (T vs. C: OR 1.073, 95 % CI 1.028-1.120; TT vs. CC: OR 1.177, 95 % CI 1.072-1.293; TT vs. CC + CT: OR 1.175, 95 % CI 1.073-1.288); Stratifying by ethnicity, significantly increased risk was only found in East Asians (T vs. C: OR 1.150, 95 % CI 1.039-1.273; TT vs. CC: OR 1.441, 95 % CI 1.145-1.814; TT vs. CC + CT: OR 1.413, 95 % CI 1.148-1.739); When stratified by menopausal status, statistically significant association was found for postmenopausal women (CT + TT vs. CC: OR 1.092, 95 % CI 1.011-1.179). In regard to A1298C polymorphism, no significant associations were found between the polymorphism and breast cancer risk. With respect to MTHFR haplotypes, significantly elevated breast cancer risk was associated with 677T-1298C for overall result (OR 1.498, 95 % CI 1.143-1.962) and for Caucasians (OR 2.088, 95 % CI 1.277-3.416) when compared with 677C-1298A; Haplotype 677C-1298C might provide higher protection than 677C-1298A in East Asians (OR 0.840, 95 % CI 0.742-0.949). The combined genotypes for C677T and A1298C produced a significant OR for the 677TT/1298AC relative to 677CC/1298AA in overall population (OR 2.047, 95 % CI 1.275-3.288); When stratified by ethnicity, significant ORs were only found for East Asians (677CC/1298CC vs. 677CC/1298AA: OR 0.686, 95 % CI 0.478-0.985; 677TT/1298AC vs. 677CC/1298AA: OR 2.181, 95 % CI 1.179-4.035). The findings suggest that the MTHFR C677T polymorphism but not A1298C, and some variants on their combined genotypes or haplotypes may be involved with the development of breast cancer.

Background Adverse pregnancy outcomes (APOs) are involved in a series of abnormal pregnancies like embryo growth arrest, spontaneous abortion, premature birth, stillbirth, fetal malformation, birth defects and other pathological pregnancy, and childbirth complications. Polymorphism of methylenetetrahydrofolate reductase gene (MTHFR, 607093) is one of the main genetic causes of APO. However, there is still debate on whether MTHFR 1298A>C, rs1801131, polymorphism is related to APO. For the lack of extensive research in the Chinese population at present, the study aim to investigate the relationship between MTHFR 1298A>C polymorphism with APO through a large number of data. Methods A total of 241 samples from patients with APO and 117 healthy controls in Yunnan province were used for MTHFR gene polymorphism analysis, with double fluorescence quantitative polymerase chain reaction (PCR). In consideration of the low frequency of MTHFR 1298C/C genotype, which might affect the statistic results, further datasets of MTHFR 1298A>C polymorphism were collected from literature and analyzed. Results No statistical difference was detected in the frequency of MTHFR1298A>C polymorphism between two groups in Yunnan. Our data showed that the frequency of MTHFR 1298A/A genotype had the decreasing tendency among Chinese population from northern to southern, as well as eastern to western of China. The frequency of MTHFR 1298A/C and 1298C/C genotypes had the adverse tendency. The frequency of MTHFR 1298C/C genotype was significantly different between two groups in Chinese populations. The significant difference was also observed in the frequency of MTHFR 1298C/C polymorphism between two groups from central China and southern China. Conclusion In summary, our data showed that MTHFR 1298C/C genotype was one of the important genetic factors of APO in China.

Background: Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have recently raised the interest as a possible thrombophilic factors. Aims: We aimed to assess the frequency of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in idiopathic venous thromboembolism (VTE) in a Romanian population and the associated risk of VTE. Study Design: We performed a case-control transversal study including 90 patients diagnosed with VTE and 75 sex- and age-matched controls. Methods: MTHFR C677T and A1298C polymorphisms were detected using PCR-RFLP method. Results: The homozygous MTHFR 677TT genotype, present in 18.8% of patients with VTE versus 6.6% of controls, was significantly associated with VTE (p= 0.021, OR= 3.26, 95%CI (1.141-9.313)). The heterozygous MTHFR A1298C genotype, presenting the highest prevalence in the VTE group (34.4%) as well as in controls (37.3%), was not associated with VTE (p=0.7). No associations were found for heterozygous MTHFR C677T (with a frequency of 32.2% in VTE and 37.3% in controls, p=0.492), respective homozygous MTHFR A1298C genotype (with a frequency of 1.1% in VTE and 2.6% in controls, p=0.456). Conclusion: Among MTHFR polymorphisms, only homozygosity for MTHFR 677TT may be considered a risk factor for VTE; the MTHFR A1298C polymorphism is not significantly associated with an increased risk of VTE. Turkish Başlık: İdiyopatik Venöz Tromboembolisi Olan Romanyalı Hastalarda Metilentetrahidrofolat Redüktaz Geninin Homozigot Polimorfizmlerinin Önemi Anahtar Kelimeler: Metilentetrahidrofolat redüktaz C677T polimorfizm, metilentetrahidrofolat redüktaz A1298C polimorfizm, venöz tromboemboli, trombofili Arka Plan: Metilentetrahidrofolat redüktaz (MTHFR) polimorfizmlerine karşı, muhtemel trombofilik faktörler olduklarından, yakın zamanda ilgi artışı olmuştur. Amaç: Romanyalı popülasyonda idiyopatik venöz tromboembolide (VTE) metilentetrahidrofolat redüktaz (MTHFR) C677T ve A1298C polimorfizmlerinin sıklığını ve VTE ile ilişkili riski değerlendirmeyi amaçladık. Çalışma Tasarımı: VTE tanısı almış 90 hasta ile yaş ve cinsiyet açısından eşleştirilmiş 75 kontrolü içeren transvers vaka-kontrol çalışması yaptık. Yöntemler: PCR-RFLP metotu kullanılarak MTHFR C677T ve A1298C polimorfizmleri saptandı. Bulgular: VTE'li hastaların %18.8'ine karşılık kontrollerin %6.6'sında mevcut olan homozigot MTHFR 677TT genotipi, VTE ile anlamlı şekilde ilişkiliydi (p= 0.021, OR= 3.26, %95CI (1.141-9.313)). VTE grubunda (%34.4) ve de kontrollerde (%37.3) en yüksek prevalansı gösteren heterozigot MTHFR A1298C genotipi VTE ile ilişkili değildi (p=0.7). Heterozigot MTHFR C677T (Sıklığı VTE'de %32.2 ve kontrollerde %37.3, p=0.492) ve homozigot MTHFR A1298C genotipi (Sıklığı VTE'de %1.1 ve kontrollerde %2.6, p=0.456) için de ilişki bulunmadı. Sonuç: MTHFR polimorfizmleri arasında sadece MTHFR 677TT homozigotluğu VTE için bir risk faktörü olarak kabul edilebilir; MTHFR A1298C polimorfizmi VTE riskinde anlamlı artış ile ilişkili değildir.

To date, case-control studies on the association between methylenetetrahydrofolate reductase (MTHFR) and diffuse large B cell lymphoma (DLBCL) have provided either controversial or inconclusive results. To clarify the effect of MTHFR on the risk of diffuse large B cell lymphoma, a meta-analysis of all case-control observational studies was performed. The fixed effects and random effects model showed that the C677T polymorphism was associated with a risk of DLBCL among East Asian populations, and A1298C polymorphism was not associated with a risk of DLBCL among Caucasian and East Asian populations. Our pooled data suggest evidence for a major role of MTHFR C677T polymorphism in the carcinogenesis of DLBCL among East Asian populations.

Made available in DSpace on 2018-12-11T17:36:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-02-01. Added 1 bitstream(s) on 2021-07-15T15:22:28Z : No. of bitstreams: 1 S2359-39972018000100021.pdf: 166618 bytes, checksum: c6efd9bc253878c7d54e958992f693f1 (MD5) Objectives: This study aimed to evaluate the frequencies of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms in obese patients with and without type 2 diabetes mellitus (T2DM). Subjects and methods: These polymorphisms were analyzed by polymerase chain reaction in 125 patients with obesity, 47 (T2DM) and 78 (Control Group). Results: No significant difference was found on comparing the T2DM and Control Groups in respect to the genotypic frequencies of the polymorphisms - (II: 13.3% vs. 12.0%; ID: 37.8% vs. 37.3; DD: 48.9% vs. 50.7%; CC: 36.2% vs. 39.0%; CT: 46.8% vs. 49.3%; TT: 17.0% vs. 11.7%), and alleles (I: 32.2% vs. 30.7%; D: 67.8% vs. 69.3%; C: 59.6% vs. 63.6%; T: 40.4% vs. 36.4%) and their synergisms in the pathophysiology of T2DM. On analyzing the T2DM Group, there were no significant differences in the presence of complications. In this population of Brazilian obese patients, no correlation was found between the ACE and MTHFR polymorphisms in the development of T2DM. Conclusion: Analyzing only the group with diabetes, there was also no relationship between these polymorphisms and comorbidities. Departamento de Biologia Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Associação Portuguesa de Beneficência Faculdade de Medicina União das Faculdades dos Grandes Lagos (Unilago) Departamento de Biologia Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp)

Wolfram syndrome-1 is a rare and severe autosomal recessive neurodegenerative disease characterized by diabetes mellitus (DM), optic atrophy, diabetes insipidus, and deafness. Poorly controlled type 1 DM increases the risk for thrombosis. However, coexistence of DM and hereditary thrombosis factors is rarely observed. Here we present the case of a 13.5-year-old, nonfollowed girl newly diagnosed with poorly controlled Wolfram syndrome on the basis of the results of clinical and laboratory examinations. On the eighth day after diabetic ketoacidosis treatment, pulmonary embolism developed in the subject. Thrombus identified in the right atrium using echocardiography was treated by emergency thrombectomy. Homozygous mutation in the methylenetetrahydrofolate reductase gene C677T, heterozygous factor-V Leiden mutation, and active protein C resistance were identified in the patient. The patient was lost because of a recurring episode of pulmonary embolism on the 86th day of hospitalization. We present this case to highlight the need for investigating hereditary thrombosis risk factors in diabetic patients in whom thromboembolism develops. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

This unreeled study aimed to examine the relationship between the genetic polymorphisms C677T in MTHFR gene and mapped this figure with other ethnic populations. The present study examined 70 Saudi females (30 mothers with DS children plus 40 healthy mothers who gave birth only to healthy children) for C677T genotypes using restriction fragment length polymorphism (RFLP) of the amplified genomic DNA. The frequencies of the combined mutant genotypes CT and TT in the MTHFR gene were modestly represented in the case mothers compared to that in controls (33% vs. 35% and 13% vs. 10%) with no significance (OR 1.1, 95% CI, 0.41–2.77, p= 0.91). The frequency of the mutant 677T allele was 28% in the case mothers and plotted as a moderate value with different ethnic populations. The present study concluded that there was a null association between the common C677T polymorphism and the increased risk of Down syndrome, but the T allele slightly supported the increase of this maternal risk. The intermediacy to previous reports may probably be due to the small sample size, gene-nutritional-environmental factors, or the consequences of much social intermarriage between some Asian, Arab peoples and the Saudi community.Keywords: Down syndrome; MTHFR gene; C677T polymorphism; Saudi mothers

Folic acid and methylenetetrahydrofolate reductase (MTHFR) may affect the development of human cancer. However, few studies have evaluated folate intake and MTHFR in susceptibility to and prognosis of patients with ovarian cancer. We conducted a prospective case-control study in 215 ovarian cancer patients and 218 controls (all Chinese) between Jan. 2004 and Jan. 2007. MTHFR C677T genotyping was done by PCR-RFLP. All patients were followed up until Dec. 2010. We found a 2.43-fold increased risk of ovarian cancer among MTHFR 677TT carriers, and a decreased risk of ovarian cancer in individuals with high folate intake (OR = 0.54, 95% CI = 0.32–0.94). Cox regression survival analysis showed that among the ovarian cancer patients, those carrying the 677TT genotype had a higher risk of death (HR = 2.17, 95% CI = 1.20–4.79), while high folate intake was associated with a lower risk of death (HR = 0.43, 95% CI = 0.33–0.88). Moreover, MTHFR 677CC carriers with higher folate intake showed a lower risk of death from ovarian cancer (HR = 0.32, 95% CI = 0.27–0.82). In summary, high folate intake may lessen susceptibility and improve the prognosis of ovarian cancer patients, while the MTHFR 677TT genotype appears to increase ovarian cancer risk and worsen its prognosis in a Chinese population.

Published data on the association between methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MTHFR A1298C polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (AC vs. AA, CC vs. AA), dominant model (CC + AC vs. AA), and recessive model (CC vs. AC + AA), respectively. A total of 26 studies including 12,244 cases and 15,873 controls were involved in this meta-analysis. Overall, no significant associations were found between MTHFR A1298C polymorphism and breast cancer risk when all studies pooled into the meta-analysis (AC vs. AA: OR = 0.99, 95% CI 0.94–1.05; CC vs. AA: OR 0.99, 95% CI 0.90–1.09; dominant model: OR = 0.99, 95% CI 0.95–1.04; and recessive model: OR = 0.98, 95% CI 0.90–1.08). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MTHFR A1298C polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.

The aim of the present study was to explore the influence of age and gender, on the association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma total homocysteine (tHcy) concentrations in patients with cardiovascular disease (CVD). Fasting tHcy and the MTHFR C677T mutation were evaluated in 98 patients with CVD, 46 were men and 52 women (aged 20-96 years). There was a significant elevation of plasma tHcy with age (75 yr: 43.6 μmol/L; p 55yr: 42.45 μmol/L; p 0.01). However, the plasma tHcy was not increased with older age in women. The frequency of the TT genotype was 19.6% in the younger patients group (>55 yr) compared with 4.7% in the older patients group (>55 yr; p 55 yr). Then, the MTHFR mutation does not seem to be associated with either high tHcy or the occurrence of CVD.

Summary We report a case of unexpected severe skin necrosis after autologous transverse rectus abdominis musculocutaneous flap breast reconstruction in a patient with homozygosis for the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene. This genetic deficiency is hypothesised as the cause of this exceptional skin necrosis. A 46-year-old woman underwent a radical mastectomy and immediate rectus abdominis musculocutaneous flap breast reconstruction. At the end of surgery, the blood supply to the flap and the abdominal wall was excellent. On the 5th postoperative day, the patient developed an extensive abdominal skin necrosis and a partial flap necrosis on the reconstructed breast. The rectus abdominis musculocutaneous flap breast reconstruction can be proposed to patients without any haemostatic defect in order to avoid life-threatening complications and unaesthetic results. This procedure requires careful patient selection, detailed preoperative planning, and complete laboratory investigations: However, mutation of the 5,10- methylenetetrahydrofolate reductase gene is too exceptional to form part of the routine preoperative investigation and can be looked for in these cases of extensive necrosis.

Polymorphisms in folate pathway genes may influence the susceptibility to acute lymphoblastic leukemia (ALL). DNA was isolated from 245 pediatric ALL patients (cases) and from 500 blood bank donors (controls). Polymorphisms in methylene-tetrahydrofolate reductase (MTHFR 677C>T, 1298A>C), methionine synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G>A), nicotinamide N-methyltransferase (NNMT IVS −151C>T), serine hydroxymethyl transferase (SHMT1 1420C>T), thymidylate synthase (TS 2R3R), and the reduced folate carrier (RFC1 80G>A) were detected. In ALL patients, an increased occurrence was observed of the RFC1 80AA variant (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3-3.2; P = .002) and the RFC1 80A allele (OR = 1.5; 95% CI, 1.1-2.1; P = .02). Likewise, the NNMT IVS −151TT genotype showed a 2.2-fold increased ALL risk (OR = 2.2; 95% CI, 1.1-4.6; P = .04). A 1.4-fold reduction in ALL risk was observed for (heterozygous or homozygous) carriers of the TS 2R allele and the MTHFR 677T allele (OR = 0.7; 95% CI, 0.5-1.0; P < .05). Furthermore, interactions between NNMT and MTHFR 677C>T and RFC1 were observed. NNMT IVS −151CC/MTHFR 677CT + TT patients exhibited a 2-fold reduction in ALL risk whereas RFC1 80AA/NNMT IVS −151CT + TT subjects had a 4.2-fold increase in ALL risk (P = .001). For the first time, we associate the RFC1 80G>A and NNMT IVS −151C>T variants to an increased ALL susceptibility.

The methylenetetrahydrofolate reductase (MTHFR) gene plays an important role in the steps involved in the processing of amino acids. The analysis of polymorphisms in the MTHFR gene has revealed associations with cancer; in particular the C677T polymorphism, which has been suggested to affect folate metabolism, DNA methylation, synthesis, and repair, and to contribute to tumor promotion in the mammary gland. We examined the role of the C677T polymorphism in the MTHFR gene by comparing the C677T genotypes of 339 healthy Mexican women with those of 497 Mexican women with breast cancer (BC). The genotype frequencies observed in the controls and patients with BC were 10 and 21% for 677TT; 41 and 36% for 677CT; and 49 and 43% for 677CC, respectively. The odds ratio (OR) for the 677TT genotype was 2.5, with a 95% confidence interval (95%CI) of 1.6-3.8; P = 0.0001. The positive association was also evident when the distributions of the 677TT genotype in control and patients affected within the following two categories were compared to alcohol consumption (OR = 0.41; 95%CI = 0.19-0.86; P = 0.018); and high level glutamate-oxaloacetate transaminase (SGOT) (OR = 0.36; 95%CI = 0.15-0.83, P = 0.017). These results suggest that the 677TT genotype of the C677T polymorphism in the MTHFR gene is associated with BC susceptibility in the Mexican population.

With great interest, we read the recent article entitled "Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk in Chinese population: a meta-analysis of 22 case-control studies" published online in Tumor Biology, 2014, 35: 1695-1701. This article suggests that methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism was significantly associated with breast cancer risk in Chinese population. The result is encouraging. Nevertheless, three key issues in this meta-analysis are worth noticing.

Objective We conducted a meta-analysis of case-controlled prospective or retrospective studies to assess the effect of MTHFR polymorphisms on the risk of developing endometrial cancer. Materials and methods PubMed, Cochrane, EMBASE, and ISI Web of Knowledge were searched (up to March 2014) for prospective or retrospective case-controlled studies that investigated the association of three MTHFR polymorphisms (rs180113 [C677T], rs1801131 [A1289C], and rs2274976 [G1793A]) with endometrial cancer. Results The patient population included subjects from three separate countries: China, Spain, and the USA. Only one study reported quantitative findings for MTHFR G1793A and, consequently, this polymorphism was not evaluated in our analysis. There were no significant associations of any MTHFR C677T or MTHFR A1298C alleles or genotypes with endometrial cancer (all p > 0.300). Conclusion This meta-analysis does not support the association of endometrial cancer with two common MTHFR polymorphisms from this patient population.

Moderate hyperhomocysteinemia is one of the risk factors of pediatric stroke. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme, which regulates homocysteine metabolism, and some polymorphisms of gene encoding this enzyme are associated with a decreased activity of the enzyme. The aim of the study was to assess an association between the A1298C polymorphism and pediatric stroke. We also evaluated a possible synergistic effect of A1298C and C677T polymorphisms of this gene. The study group consisted of 88 children after ischemic stroke, 142 of their parents and 111 controls. The A1298C polymorphism was genotyped using the restriction fragment length polymorphism method. We used 2 study designs: a case–control model and a family-based association test. The Statistica 7.1 and EpiInfo 6 softwares were used in all analyses. We did not observe any statistically significant differences either in the transmission of the A allele in the family-based test or in the frequency of the A allele in the patients group compared with the controls. We also did not notice any significant additive or synergistic effects between the A1298C and C677T polymorphisms. An analysis of the results obtained in this study and a critical review of previously published studies indicate that the A1298C polymorphism of the MTHFR gene is not related to ischemic stroke in children.

Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both stroke subtypes in patients with methylenetetrahydrofolate reductase gene polymorphisms. Therefore, we examined whether the C677T and A1298C polymorphisms of MTHFR gene are genetic risk factors for both ischemic and hemorrhagic stroke in a Turkish Caucasian population. In a case-control study, 120 total unrelated stroke patients (92 ischemic stroke, 28 hemorrhagic stroke), and 259 healthy controls were genotyped for C677T and A1298C polymorphisms of the MTHFR gene using a PCR-RFLP based-method. The MTHFR 1298C allele (chi(2)=8.589; P=0.014), C1298C genotype (OR=2.544; P=0.004), and C677C/C1298C compound genotype (OR=3.020; P=0.001) were associated with overall stroke. The MTHFR 1298C allele (chi(2)=11.166; P=0.004), C1298C genotype (OR=2.950; P=0.001), and C677C/C1298C compound genotype (OR=3.463, P=0.0001) were strongly associated with ischemic stroke. Interestingly however, the MTHFR 677T allele (chi(2)=6.033; P=0.049), T677T genotype (OR=3.120; P=0.014), and T677T/A1298A compound genotype (OR=4.211; P=0.002) were associated with hemorrhagic stroke. In conclusion, the C677T and A1298C polymorphisms of the MTHFR gene are genetic risk factors for hamorrhagic and ischemic stroke respectively, independent of other atherothrombotic risk factors.

BACKGROUND: Several studies have suggested a protective effect of folic acid (FA) on congenital heart anomalies. Down syndrome (DS) infants are known to have a high frequency of heart anomalies. Not all children with DS suffer from heart anomalies, which raises the question whether maternal factors might affect the risk of these anomalies. Our objectives were to investigate whether first-trimester FA use protects against heart anomalies among DS children. METHODS: Women with liveborn DS children participating in the Slone Epidemiology Center Birth Defects Study between 1976 and 1997 were included. We performed case-control analyses using DS, with heart anomalies as cases and DS, without heart anomalies as controls. Subanalyses were performed for defects that have been associated with FA in non-DS populations (conotruncal, ventricular septal [VSD]) and for those that are associated with DS (ostium secundum type atrial septal defects [ASD] and endocardial cushion defects [ECD]). Exposure was defined as the use of any FA-containing product for an average of at least 4 days per week during the first 12 weeks of pregnancy, whereas no exposure was defined as no use of FA in these 12 weeks. RESULTS: Of the 223 cases, 110 (49%) were exposed versus 84 (46%) of the 184 controls. After adjustment for possible confounders, no protective effect of FA was found on heart anomalies overall (OR 0.95, 95% CI: 0.61-1.47) nor separately for conotruncal defects, VSDs, ASDs, or ECDs. CONCLUSIONS: Our study does not show a protective effect of FA on heart anomalies among infants with DS.

This review examines the relationship between hyperhomocysteinemia, a risk factor for vascular disease, and carotid intima-media thickness (CIMT), a valid marker of generalized atherosclerosis and future vascular disease risk. The relationship between two important determinants of hyperhomocysteinemia in the general population-folate status and the 677C --> T methylenetetrahydrofolate reductase (MTHFR) polymorphism-and CIMT is also covered. Methods: We searched literature databases for articles examining homocysteine and CIMT published before September 2003. Results: We identified 54 studies. Observational studies generally failed to demonstrate a relationship between homocysteine and CIMT in homocystinuric, uremic, hypercholesterolemic or non-insulin-dependent diabetes mellitus patients or in subjects with insulin insensitivity. Weak associations, but usually only in certain sub-populations were found in vascular disease patients and in population-based studies. B vitamins reduce the progression of CIMT in renal transplant recipients and vascular disease patients as demonstrated by two trials. The majority of studies demonstrated increased CIMT in individuals with the MTHFR 677TT genotype. Folate status showed no relation to CIMT. Discussion: In non-patient populations, hyperhomocysteinemia is weakly associated with CIMT. The association of the 677C --> T MTHFR polymorphism with CIMT further supports this finding. Lastly, folate levels may need to reach a critically low status before an association can be found between folate and CIMT. Larger trials in various population types are needed to determine whether folate alone or in combination with Vitamins B-6 and B-12 Will slow down or even reverse atherosclerotic progression. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

To evaluate whether the C677T polymorphism of the methylenetetrahydofolate reductase (MTHFR) gene is consistently associated with hypertension in pregnancy.Meta-analysis of studies comparing women with and without hypertension in pregnancy for the C677T MTHFR polymorphism.Studies were identified with MEDLINE and EMBASE searches complemented with perusal of bibliographies of retrieved articles and communication with investigators. Between-study heterogeneity was estimated and data were combined with random effects models. Sensitivity analyses examined the effect of population and disease characteristics. Bias diagnostics evaluated the evolution of the postulated genetic effect over time and the potential for publication bias.Across 23 comparisons (3169 hypertensive women, 3044 controls), having the T allele (TT or CT) increased the odds of hypertensive disease of pregnancy by 1.21-fold (95% confidence interval, 1.01-1.44), but there was large between-study heterogeneity (P = 0.003). The results were similar and heterogeneity persisted when sensitivity analyses were limited to studies of Caucasian populations, or those of patients with significant proteinuria. While patients with diastolic hypertensionor = 110 mmHg showed an odds ratio of 1.41 (95% confidence interval, 1.03-1.73), no association was seen in patients with less severe diastolic hypertension (odds ratio, 1.00; 95% confidence interval, 0.61-1.65). Early published studies tended to show stronger associations than the subsequent studies.While bias cannot be excluded, the meta-analysis suggests that the T allele may increase the risk of severe diastolic hypertension during pregnancy.

Background. A methylenetetrahydrofolate reductase (MTHFR) polymorphism (1317T → C) that occurs commonly in black African individuals prompted this study to establish whether this polymorphism, alone or in association with other MTHFR variants, is associated with preeclampsia in black South African women. Methods. A group of 204 black women with preeclampsia was examined for the 677C → T, 1298A → C and 1317T → C MTHFR polymorphic alleles using standard techniques. Also examined were women with early-onset preeclampsia ( n = 67) and gestational hypertension ( n = 78). Results were compared with 338 ethnically matched normotensive pregnant women who had normal full-term gestations. Results. No differences in the 677T → C or 1298A → C MTHFR alleles were found between the study groups and controls; very few women were homozygous for either variant allele. Significant differences were observed for the 1317T → C polymorphism: only 39% of preeclamptics were homozygous for the T allele compared with 52% of the con...

Methotrexate (MTX) is an effective and toxic chemotherapeutic drug in the treatment of pediatric acute lymphoblastic leukemia(ALL). In this prospective study, we aimed to identify metabolic and genetic determinants of MTX toxicity. One hundred and thirty-four Dutch pediatric ALL patients were treated with four high infusions MTX (HD-MTX: 5 g m -2) every other week according to the DCOG-ALL-10 protocol. Mucositis (National Cancer Institute grade ≥3) was the most frequent occurring toxicity during the HD-MTX phase (20%) and occurred especially after the first MTX course. Mucositis was not associated with plasma MTX, plasma folate or plasma homocysteine levels. Patients with mucositis had higher erythrocyte folate levels at the start of protocol M than patients without mucositis (median 1.4 vs 1.2 μmol l -1, P

WOS: 000343723600063, PubMed ID: 25124620, Background: In this case-control study, we aimed to investigate the relationship between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and lung cancer. Materials and Methods: Total 200 individuals including 100 patients with lung cancer and 100 controls were analyzed. Genotyping of MTHFR C677T was performed using PCR and RFLP methods. Results: The majority of the patients were men and 90% were smokers. We found that the risk ratio for development of LC was 13-times higher in smokers compared with non-smokers between patient and control groups in our study (OR:13.5, 95% CI:6.27-29.04, p:0.0001). Besides, the risk ratio for development of LC was nine times higher in individuals with cancer history in their family than those without cancer history (OR:9.65, 95% CI:2.79-33.36; p:0.0001). When genotype distributions and allele frequencies were analyzed in the study groups, no significant difference was apparent (chi(2):0.53, p=0.76). In addition, no correlation between genotypes of MTHFR C677T polymorphism and histological type of LC was found (chi(2):0.99, p=0.60). Conclusions: These results suggest that there was no association between the MTHFR C677T polymorphism and lung cancer in the Turkish population.

This paper examines whether there is a relationship between a common mutation in the methylenetetrahydrofolate reductase gene, MTHFR*val, and the risk of colorectal cancer, with or without lymph node metastases. MTHFR genotypes were ascertained from peripheral leukocyte samples obtained from 200 colorectal patients, including TMN stages I-VI, and from 460 healthy, unrelated adults without colorectal cancer, who served as controls. The frequency of homozygosity for the MTHFR*val/*val genotype among the colorectal cancer patients was lower (14.0%) than among controls (16.1%). The latter finding results in an estimated MTHFR*val allele frequency of 0.41. The MTHFR*val allele (677CT) reduces colorectal risk slightly [odds ratio (OR), 0.87]. However, there was a significantly higher incidence of metastatic lymph nodes per case in MTHFR*val/*val patients, when compared with MTHFR*ala/*ala controls (6.9 +/- 1.55 vs. 3.7 +/- 0.57, p = 0.003). These results suggest that the MTHFR genotype might be of prognostic significance in colorectal carcinoma.