Methylenetetrahydrofolate Reductase C677T Gene Polymorphism Research Articles

CT genotype of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is protector factor of major depressive disorder in the Tunisian population: a case control study.

BackgroundMajor depressive disorder (MDD) is a common psychiatric disorder with considerable mortality. Death from unnatural causes, largely suicidal or quasi-suicidal, has a particularly high risk for the functional disorders, especially depression and schizophrenia. One of the prospective risk factors for this disease is hyperhomocysteinemia and folate deficiency. The methylenetetrahydrofolate reductase (MTHFR) gene encodes for a 5-methylenetetrahydrofolate reductase involved in folate metabolism and neurotransmitter synthesis. The aim of this research is to study the association between the C677T polymorphism of MTHFR gene and depression in Tunisian population, to explore their relationship with clinical and therapeutic characteristics of this disease. And it may lead to discover a novel marker to identify a patient with a higher risk of development of depressive disorder to be. This marker can be used for better therapeutic management and prevent disease installation.MethodsOur study included 208 depressive patients, 187 controls aged between 44.1 ± 13.5 and 38.9 ± 13.2 years, respectively. MTHFR gene polymorphisms were determined by PCR–RFLP (polymerase chain reaction–restriction fragment length polymorphism).ResultsNo significant difference was detected in the distribution of the genotype frequencies of MTHFR C677T polymorphisms (χ2 = 5.443, df = 2, p = 0.066) between patients and controls. But when we study the risk of these genotypes, CT genotype is significantly more frequent in controls compared to patients, it may be a protection from depression (OR = 0.655, CI 95 % = 0.432–0.995, p = 0.047, OR* = 0.638, CI 95 %* = 0.415–0.983, p* = 0.04, before and after adjustment). Women, TT Genotype can increase four times the risk to be depressive. Addictive behavior seems to be associated with CT genotype and there was no significant association between clinical and therapeutic characteristics and this polymorphism.ConclusionThis paper is the first study to prove that CT genotype of MTHFR C677T polymorphism may protect from depression and TT genotype seems to be associated with women’s depression. Further studies are required with other polymorphisms and biochemical factors that must be investigated to clarify the implication of MTHFR C677T polymorphism in the pathophysiology of depression.

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

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

MTR, MTRR, and MTHFR Gene Polymorphisms and Susceptibility to Nonsyndromic Cleft Lip With or Without Cleft Palate.

To examine the associations of methionine synthase (MTR), methionine synthase reductase (MTRR), and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with the susceptibility to nonsyndromic cleft lip with or without cleft palate (NSCL/P). Between May 2012 and August 2014, 147 NSCL/P patients (case group) and 129 healthy volunteers (control group) were recruited for the study. The MTR A2756G, MTRR A66G, MTHFR C677T and MTHFR A1298C polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism. Haplotype analyses were performed with SHEsis software. Logistic regression analysis was used to evaluate the possible risk factors for NSCL/P. Generalized multifactor dimensionality reduction (GMDR) was applied to detect gene-gene interactions. MTR A2756G, MTRR A66G, and MTHFR C677T gene polymorphisms were associated with the risk of NSCL/P (all p < 0.05). Logistic regression analysis revealed that MTR A2756G, MTR RA66G, and MTHFR C667T might increase the risk of NSCL/P (odds ratio [OR] = 0.270, 95% confidence interval [95% CI] = 0.106-0.689; OR = 0.159, 95% CI = 0.069-0.368; OR = 0.343, 95% CI = 0.139-0.844). The CA haplotype in the MTHFR gene may serve as a protective factor for NSCL/P (OR = 0.658, 95% CI = 0.470-0.923), and the TA haplotype might be a risk factor (OR = 2.001, 95% CI = 1.301-3.077). GMDR revealed that the optimal models were two- and four-dimensional models with prediction accuracies of 75.73% (p = 0.001) and 77.21% (p = 0.001) and the best cross-validation consistencies of 10/10 and 10/10, respectively. MTR A2756G, MTRR A66G, and MTHFR C677T polymorphisms may be related to NSCL/P, and interactions were detected between the MTR A2756G, MTRR A66G, and MTHFR C677T and A1298C polymorphisms.

Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G gene polymorphisms and associated risk of cardiovascular diseases: A study from Jammu region

AimPotent risk factors at both genetic and non-genetic levels are accountable for susceptibility and instigation of different cardiovascular phenotypes. Recently, homocysteine is being identified as an important predictor for cardiovascular diseases. Homocysteine remethylation plays a key role in the synthesis of methionine and S-adenosine methionine. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) genes are known to regulate the homocysteine remethylation reaction and higher homocysteine level is significantly associated with diverse cardiovascular phenotypes. In this context, we aimed to carry out a study on the association of MTHFR (C677T) and MTR (A2756G) gene polymorphism with CVD in population of Jammu region of J&K state. Materials and methodsA total of 435 individuals were enrolled (195 CVD patients and 240 controls) for the case–control study. Genotyping of MTHFR C677T and MTR A2756G gene polymorphism was done by PCR-RFLP technique. Biochemical parameters were estimated by biochemical analyser. ResultsMetabolic variables such as serum LDL-C, TC and TG were significantly higher in patients (p<0.0001), whereas serum HDL-C was higher in controls. Majority of the patients were having history of hypertension (57.44%; p<0.0001) as a concomitant condition. The evaluation of genetic association showed that, MTHFR C6877T (OR: 8.89, 95% CI: 2.01–39.40) and MTR A2756G (OR: 1.48, 95% CI: 1.09–2.00) polymorphisms associated with higher risk of CVD. ConclusionThe present study reveals significant differences in nongenetic variables among patients and control as well as association of gene polymorphisms with CVD risk.

Geographical and Ethnic Distributions of the MTHFR C677T, A1298C and MTRR A66G Gene Polymorphisms in Chinese Populations: A Meta-Analysis.

BackgroundThe geographical and ethnic distributions of the polymorphic methylenetetrahydrofolate reductase (MTHFR) mutations (C677T and A1298C) and methionine synthase reductase (MTRR) mutation (A66G) remain heterogeneous in China. The goal of this study was to estimate the pooled frequencies of the alleles and associated genotypes of these gene polymorphisms among healthy populations in Mainland China.Objective and MethodsWe systematically reviewed published epidemiological studies on the distributions of 3 genetic variants in Chinese healthy populations living in Mainland China through a meta-analysis. The relevant electronic databases were searched. All of the raw data of the eligible citations were extracted. The frequency estimates were stratified by geography, ethnicity and sex.ResultsSixty-six studies were identified with a total of 92277 study participants. The meta-analysis revealed that the frequencies of the MTHFR C677T, A1298C, and MTRR A66G gene polymorphisms varied significantly between different ethnic groups and along geographical gradients. The frequencies of the 677T allele and 677TT genotype increased along the southern-central-northern direction across Mainland China (all Pvalues≤0.001). The frequencies of the 1298C, 1298CC, 66G and 66GG genotypes decreased along the south-central-north direction across the country (all Pvalues≤0.001).ConclusionsOur meta-analysis strongly indicates significant geographical and ethnic variations in the frequencies of the C677T, A1298C, and A66G gene polymorphisms in the folate metabolism pathway among Chinese populations.

Relationship between MTHFR C677T and A1298C gene polymorphisms and complications of type 2 diabetes mellitus in an Emirati population

PurposeType 2 diabetes mellitus (T2DM) is the most common form of diabetes with clinical consequences giving rise to chronic multiple organ complications. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms are genetic variations that have been linked to T2DM, and micro/macrovascular complications. The link between MTHFR and T2DM however is strongly dependent on the ethnic group studied. The objective of this study was to investigate the possible association between two MTHFR polymorphisms (C677T and A1298C) and T2DM and specifically examine if there are any associations with clinical and demographic characteristics among patients in the United Arab Emirates (UAE). MethodsThe study included 169 T2DM patients and 209 healthy controls. Genomic DNA was isolated and genotyped using TaqMan real-Time PCR assays for the MTHFR C677T and A1298C polymorphisms. ResultsThere were no significant differences in genotype and haplotype distributions observed between groups. A significant association was observed between the C677T polymorphism and history of cerebrovascular accident (CVA) (p=0.0330), history of nephropathy (p=0.0280) and levels of LDL cholesterol (p=0.0409). Also, the A1298C polymorphism was associated with hypertriglyceridemia (p=0.0305) in T2DM patients. ConclusionThese findings demonstrate that the MTHFR gene polymorphisms are not related to T2DM in the Emirati population. However, these polymorphisms can be used as risk markers for CVA, nephropathy, high LDL cholesterol and triglycerides in T2DM patients and allow timely treatment.

Correlation between homocysteine level and MTHFR C677T polymorphism in cerebral infarction patients with or without diabetes mellitus

Objective To study the correlation between serum homocysteine(Hcy) level and C677T polymorphism of methylenetetrahydrofolate reductase(MTHFR) gene C677T polymorphism(rs1801133) in patients with cerebral infarction, and feature of rs1801133 polymorphism and serum Hcy level in cerebral infarction patients with or without diabetes mellitus. Methods Case-control study. Five hundred and fifty six patients with cerebral infarction admitted to China-Japan Friendship Hospital from January 2014 to January 2015 were included as the case group while 275 subjects from medical examination center without cerebral infarction and diabetes mellitus matched with the case group. MTHFR C677T polymorphism was determined by pyrosequencing and serum Hcy was determined by circulating enzymatic. Chi-square test was used to analyze the distribution of genotype in different group; ANVOA was used to analyze the Hcy level with different genotype in patients with cerebral infarction, and LSD-t was used to pairwise comparison. Results Among the 556 patients with cerebral infarction , TT genotype were 202 cases(36.33%), CT genotype were 257 cases(46.22%), CC genotype were 97 cases(17.45%). The T allele frequencies were 59.44%, higher than the control group T allele frequencies 46.91%(χ2=23.385, P 0.05), while the level of serum Hcy in Cerebral infarction patients with diabetes mellitus (18.16±12.90)μmol/L is lower than Cerebral infarction patients without diabetes mellitus(23.47±19.53) μmol/L in TT genotype(F=4.652, P<0.05). Conclusions MTHFR TT genotype was related to serum hyperhomocysteine, and maybe save as the risk of cerebral infarction.The Hcy level in TT genotype cerebral infarction patients with DM is lower than the same genotype patients without DM.(Chin J Lab Med, 2016, 39: 205-209) Key words: Brain infarction; Methylenetetrahydrofolate reductase; Homocysteine; Diabetes mellitus; Polymorphism, genetic

Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility.

Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms - 'MTHFR', 'C677T', in combination with 'Autism'. Pooled OR with its corresponding 95% CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion in the present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (ORTvs.C=1.48; 95% CI: 1.18-1.86; P=0.0007; ORTT + CT vs. CC=1.70, 95% CI=0.96-2.9, p=0.05; ORTT vs. CC=1.84, 95% CI=1.12-3.02, p=0.02; ORCT vs.CC=1.60, 95% CI=1.2-2.1, p=0.003; ORTT vs.CT+CC=1.5, 95% CI=1.02-2.2, p=0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (ORTvs.C=1.43; 95% CI=1.1-1.87; p=0.009) and Asian population (ORTvs.C=1.68; 95% CI=1.02-2.77; p=0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism.

Association between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and risk of ischemic stroke in North Indian population: A hospital based case–control study

ObjectiveThe aim of the present case–control study was to determine the association between methylene tetrahydrofolate reductase (MTHFR) C677T (rs1801133) gene polymorphism and risk of ischemic stroke (IS) in North Indian population. MethodsPatients with IS and age-sex matched controls were recruited from Neurology Outpatient Department and Ward of All India Institute of Medical Sciences, New Delhi, India. Genotyping was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. PCR–RFLP results of nine randomly selected samples were confirmed by DNA sequencing. Genotypic and allelic distributions were compared between cases and controls. Statistical analysis was done by STATA, version 13.0 software. ResultsHypertension, diabetes, dyslipidemia, low socioeconomic status and family history of stroke were found to have an independent association with the risk of IS after adjusting for potential confounding factors. Mean age of cases and controls were 52.83±12.59 and 50.97±12.70years. Multivariate logistic regression analysis showed an independent association between MTHFR C677T gene polymorphism and risk of IS (OR 1.91; 95% CI 1.07–3.41; p=0.028) under dominant model [CT+TT vs. CC]. MTHFR C677T gene polymorphism was found to be independently associated with risk of small vessel disease (SVD) after adjustment for potential confounding factors [OR 2.51; 95% CI 1.30–4.85; p=0.006] under the dominant model. ConclusionFindings of the present study suggest that MTHFR C677T gene polymorphism might be a risk factor of IS mainly for SVD subtypes of IS in North Indian population. Further large prospective studies are required to confirm these findings.

English

Objective: To observe the relationship between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and homocysteine levels in cerebral palsy (CP) children. Methods: This cross-sectional study was conducted in several hospitals, school for children with special needs, and rehabilitation centers in Bandung from March to November 2014, on children with CP aged 4–14 years who met the inclusion criteria. Genotyping was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and direct sequencing. Homocysteine serum level was measured using chemiluminescent microparticle immunoassay (CMIA) method. Statistical analysis was conducted using t test. Results: In this study, 150 CP children had MTHFR C677T gene polymorphism with a frequency of 18%, consisting of TT homozygotes (4%), CT heterozygotes (14%), and T allele (11%. The mean serum level of homocysteine in CP with C677T MTHFR gene polymorphism was 8.22 (±1.89) µmol/L, higher than those without polymorphism (p=0.046). Conclusions: A relationship between MTHFR C677T gene polymorphism and homocysteine level in children with cerebral palsy is found in this study. Keywords: Cerebral palsy, homocysteine, methylenetetrahydrofolate reductase polymorphism DOI: 10.15850/ijihs.v4n1.682

Role of MTHFR C677T gene polymorphism in the susceptibility of schizophrenia: An updated meta-analysis.

Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme of folate/homocysteine metabolic pathway. C677T polymorphism of MTHFR gene was reported as risk factor for congenital defects, metabolic and neuropsychiatric disorders. Numerous case-control studies investigated C677T polymorphism as risk factor for schizophrenia but results of these studies were contradictory. To draw a conclusion, a meta-analysis of all available case-control studies was performed. PubMed, Google Scholar, Springer Link and Elsevier databases were searched for eligible case-control studies. Pooled odds ratio with 95%CI was used as an association measure and all statistical analyses were performed by Open Meta-Analyst and MIX software. Total 38 studies with 10,069 cases and 13,372 controls were included in the present meta-analysis. Results of meta-analysis showed significant associated between C677T polymorphism and risk of schizophrenia (ORTvsC=1.18, 95%CI=1.10-1.27, p=<0.001; ORCTvsCC=1.10, 95%CI=1.04-1.17, p=<0.001; ORTTvsCC=1.40, 95%CI=1.20-1.64, p=<0.001; ORTT+CTvsCC=1.19, 95%CI=1.09-1.30, p=<0.001). We also performed subgroup and sensitivity analyses. Subgroup analysis was done according to ethnicity and significant association was found between C677T polymorphism and risk of schizophrenia in all three ethnic populations-African (OR=2.51; 95%CI=1.86-3.40; p=<0.001), Asian (OR=1.21; 95%CI=1.10-1.33; p=<0.001) and Caucasian (OR=1.07; 95%CI=1.01-1.14; p=0.01). In conclusion the results of the present meta-analysis suggested that the MTHFR C677T polymorphism is a risk factor for schizophrenia.

Association between the MTHFR C677T gene polymorphism and essential hypertension in South West Cameroon.

The association of the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and essential hypertension has been reported but with controversial results in diverse populations in Asia and Europe, thereby suggesting a dependency on ethnicity. The aim of this study was to investigate the association between the MTHFR C677T polymorphism and essential hypertension in a Cameroonian population (Bantu ethnic group) of the South West Region. Analysis of anthropometric and biochemical data in hypertensive and normotensive subjects revealed that age, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol, serum total cholesterol, and triglycerides are independent risk factors for essential hypertension. Substitution of thymine for cytosine at position 667 of the MTHFR gene was determined by polymerase chain reaction-restriction fragment length polymorphism. Genotype frequencies were found to be 7.3% CC, 58.5% CT, and 34.1% TT for hypertensive subjects compared to 90.0% CC, 10.0% CT, and 0.0% TT for normotensives. Allele frequencies were obtained as 36.6% C and 63.4% T for hypertensive subjects and 95.0% C and 5.0% T for normotensive subjects. These results reveal that the T allele predisposes individuals to hypertension. Therefore, there is an association between variants of the MTHFR gene and hypertension in Cameroonian patients from the South West region.

Methylenetetrahydrofolate Reductase Gene C677T Polymorphism and Its Association with Ovary Cancer

Methylenetetrahydrofolate reductase (MTHFR) is a vital enzyme involved in folate metabolism; a single nucleotide polymorphism (SNP) C677T has been reported to be linked with altered incidences of several diseases. The association between ovary cancer and the MTHFR gene C677T polymorphism has been investigated in several case-control studies. These studies rendered contradictory results, to shed light on these inconclusive findings, a meta-analysis of all available studies relating the C677T polymorphism to the risk of ovary cancer was conducted. The following electronic databases were searched without language restrictions: Pubmed, Google Scholars, Elsevier and Springer Link up to December, 2014. Odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated. Meta-analysis was performed using Mix version 1.7. Eleven studies were finally included in present meta-analysis, which contained 5922 individuals with ovary cancer and 5235 healthy controls. There was not significant relationship between MTHFR C677T polymorphism and ovary cancer under allele contrast (OR: 1.05, 95% CI: 0.99-1.11), dominant (OR: 1.02, 95% CI: 0.91-1.13), recessive (OR: 0.99, 95% CI: 0.90-1.08), homozygous (OR: 0.99, 95% CI: 0.86-1.14) and co-dominant/heterozygous (OR: 1.02, 95% CI: 0.91-1.14) genetic models. Subgroup analysis also reached similar results. Sensitivity analysis indicated that the overall result were dependable. In conclusion, results of present meta-analysis showed that MTHFR gene C677T polymorphism is not a risk factor for Ovary cancer.

Association between C677T and A1298C polymorphisms of the MTHFR gene and risk of male infertility: a meta-analysis.

Published studies on the association between the C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene and male infertility risk are controversial. To obtain a more precise evaluation, we performed a meta-analysis based on published case-control studies. We conducted an electronic search of PubMed, EMBASE, the Cochrane Library, the Web of Science, and the China Knowledge Resource Integrated Database for papers on MTHFR gene C677T and A1298C polymorphisms and male infertility risk. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were used to assess the strength of association in homozygote, heterozygote, dominant, recessive, and additive models. Statistical heterogeneity, test of publication bias, and sensitivity analysis were carried out using the STATA software (Version 13.0). Overall, 21 studies of C677T (4505 cases and 4024 controls) and 13 studies of A1298C (2785 cases and 3094 controls) were included in this meta-analysis. For C677T, the homozygote comparison results were OR = 1.629, 95%CI (1.215- 2.184), and the recessive model results were OR = 1.462 (1.155- 1.850). For A1298C, the homozygote comparison results were OR = 1.289 (1.029-1.616), and the recessive model results were OR = 1.288 (1.034-1.604). In conclusion, the current meta-analysis showed that the MTHFR C677T polymorphism was associated with a significantly increased male infertility risk in the Asian and overall populations, but not in the Caucasian population, and there was a significant association between the A1298C polymorphism and male infertility risk in the Asian, Caucasian, and overall groups.

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

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

Association of the methylenetetrahydrofolate reductase gene C677T polymorphism with the risk of male infertility: a meta-analysis

Several molecular epidemiological studies have been conducted to examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and male infertility susceptibility, but the results remain inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. In this meta-analysis, a total of 26 case–control studies including 5659 infertility cases and 5528 controls were selected to evaluate the possible association. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of association of C677T polymorphism with male infertility in the additive model, dominant model, recessive model and allele-frequency genetic model. In the overall analysis, the frequency of the 677T allele was significantly associated with male infertility susceptibility (OR = 2.32, 95%CI = 2.04–2.65 for TT vs. CC genotype; OR = 1.09, 95%CI = 1.00–1.19 for CT vs. CC genotype; OR = 1.19, 95%CI = 1.10–1.29 for CT/TT vs. CC genotype; OR = 1.54, 95%CI = 1.36–1.74 for TT vs. CC/TT genotype; OR = 1.22, 95%CI = 1.15–1.30 for T vs. C allele). A subgroup analysis of the subjects showed that significantly strong association between MTHFR C677T polymorphism and male infertility was present only in Asians, but not in Caucasians. Additionally, MTHFR C677T was associated with a significant increase in the risk of azoospermia in all genetic models. Meanwhile, no significantly increased risks of oligoasthenotertozoospermia (OAT) were found in most of the genetic models. In conclusion, this meta-analysis is in favor that the MTHFR C677T polymorphism is capable of causing male infertility susceptibility, especially in Asians and the subgroup of azoospermia.

The association between methylenetetrahydrofolate reductase gene C677T polymorphisms and breast cancer risk in Chinese 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.

Association between maternal, fetal and paternal MTHFR gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss: a comprehensive evaluation.

Numerous studies have investigated the associations between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss (RPL); however, the results remain controversial. The aim of this study is to drive a more precise estimation of association between MTHFR gene polymorphisms and risk of RPL. We searched PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated Database for papers on MTHFR gene C677T and A1298C polymorphisms and RPL risk. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygous model, heterozygous model, dominant model, recessive model and an additive model. The software STATA (Version 13.0) was used for statistical analysis. Overall, 57 articles were included in the final meta-analysis. In maternal group the MTHFR C677T polymorphism showed pooled odds ratios for the homozygous comparison [OR=2.285, 95% CI (1.702, 3.067)] and the MTHFR A1298C polymorphism showed pooled odds ratios for recessive model [OR=1.594, 95% CI (1.136, 2.238)]. In fetal group the MTHFR C677T polymorphism showed pooled odds ratios for dominant model [OR=1.037, 95% CI (0.567, 1.894)] and the MTHFR A1298C polymorphism showed pooled odds ratios for dominant model [OR=1.495, 95% CI (1.102, 2.026)]. In summary, the results of our meta-analysis indicate that maternal and paternal MTHFR gene C677T and A1298C polymorphisms are associated with RPL. We also observed a significant association between fetal MTHFR A1298C polymorphism and RPL but not C677T.

Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms in oral squamous cell carcinoma insouth-east Iran.

Methylenetetrahydrofolate reductase (MTHFR) gene encodes an essential enzyme involving in folate metabolism. Due to the role of folate in DNA integrity, polymorphisms of MTHFR are interesting targets for cancer risk studies. Our goal was to evaluate the prevalence of MTHFR C677T and A1298T single nucleotide polymorphisms in oral squamous cell carcinoma (OSCC). The study was conducted on 57 OSCC patients diagnosed within 2004-2013 along with 62 non-OSCC subjects. DNA was extracted by standard kit protocol. Subsequently, tetra-ARMS (amplification refractory mutation system)-PCR was applied to identify the selected polymorphisms. Data showed that CT and TT genotypes of C677T polymorphisms significantly increased the risk of OSCC [odds ratio (OR)=2.2, 95% CI: 1-5, P=0.04]. Although allelic distribution was not significantly different between patients and controls, T allele of C677T polymorphism was closely associated with the risk of OSCC (OR=2.5; 95% CI: 0.9-6.9; P=0.07). Results indicated that C677T/A1298C: CC/AC and C677T/A1298C: CC/AA haplotypes were the most common combinations in OSCC patient and control groups, respectively. (OR=1.5, 95% CI: 0.6-3.8, P>0.05). Our results highlight the possible impact of C677T polymorphism in increasing the risk of OSCC development.

Association of methylenetetrahydrofolate reductase gene polymorphisms with polycystic ovary syndrome

To assess the association of C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene with the susceptibility to polycystic ovary syndrome (PCOS). Blood samples of 115 PCOS patients and 58 fertile women (for whom PCOS has been excluded) were collected for DNA extraction. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for determining the C677T and A1298C polymorphisms. A database has been set up with Epidata and a significance test was performed with a statistical analysis system. A significant difference has been found in the allele frequencies of MTHFR gene 677 C and T polymorphisms between the two groups (P<0.01), for which T allele has increased the risk for PCOS by 2.06 times. Heterozygous and homozygous genotypes at position 677 (CT and TT) were more common among PCOS cases than controls, with an OR of 3.91 (95%CI: 1.70-8.97) and 4.39 (95%CI: 1.77-10.89), respectively. There was no statistical difference in genotypic distribution of MTHFR gene A1298C polymorphism (P>0.05). In the PCOS group, there was a significant difference with an OR of 6.40 (95%CI: 1.71-23.95) for an increased risk of insulin resistance in homozygous C677T mutations (TT) compared with the wild genotype (CC, P<0.01). The PCOS group and the control group also differed significantly in their red blood cell folate levels (P<0.01), but not in serum vitamin B12 and homocysteine levels (P>0.05). MTHFR gene C677T polymorphism is associated with PCOS, for which CT and TT genotypes can increase the risk of PCOS. The TT genotype can also increase the risk of insulin resistance in PCOS patients. The A1298C polymorphism of the MTHFR gene is not associated with the occurrence of PCOS. The folate level in red blood cells of PCOS patients is lower, for whom folate should be supplemented.