Synergistic effect of MTHFR C677T and F2 G20210A polymorphisms on ischemic stroke.
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ABSTRACT:
SUBMITTER: They-They TP
PROVIDER: S-EPMC5562548 | biostudies-other | 2013 Dec
REPOSITORIES: biostudies-other
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Project description:The aim of this study was to investigate the relationship between the combined effect of MTHFR C677T (rs1801133) and EPHX2 G860A (rs751141) polymorphism and ischemic stroke in Chinese T2DM patients. This case-control study included a total of 626 Chinese T2DM patients (236 T2DM patients with ischemic stroke and 390 T2DM patients without ischemic stroke). The rs1801133 and rs751141 were genotyped using real-time polymerase chain reaction. Statistical analysis was performed with SPSS 17.0. Results showed that the combined effect of MTHFR TT and EPHX2 GG or GA + AA genotype has a higher risk of ischemic stroke compared with the control group (combined effect of MTHFR CC and EPHX2 GA + AA genotypes; OR = 3.46 and OR = 3.42, resp.; P = .001 and P = .002, resp.). The A allele showed marked association with a lower risk of ischemic stroke in patients with the lowest Hcy levels under additive, recessive, and dominant genetic models (OR = 0.45, OR = 0.11, and OR = 0.44, resp.; P = .002, P = .035, and P = .008, resp.), which was not observed in medium or high Hcy level groups. In conclusion, the T allele of rs1801133 and the G allele of rs751141 may be risk factors of ischemic stroke in the Chinese T2DM population.
| S-EPMC5376931 | biostudies-literature
Project description:Methylene Tetrahydrofolate Reductase (MTHFR) catalyzes the conversion of methylene tetrahydrofolate to methylte trahydrofolate. The 677th nucleotide of the MTHFR gene is often regarded as a risk factor of cardiovascular disease. Previous studies demonstrated an elevated risk of ischemic stroke with the MTHFR677TT genotype. In this study, we employed a plasma proteomics method to investigate the connection between the polymorphism of the target nucleotide and stroke. In total, 28 protein spots were differentially expressed between the two groups, and of which, 25 protein spots were up-regulated and 3 were down-regulated. Five randomly selected spots were successfully identified as Haptoglobin (HPT) and Transferrin (TRFE). A functional analysis indicated that most of the differential expressed proteins (DEPs) were related to the inflammatory immune response. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEPs were involved in the complement cascade reaction. Meanwhile, protein-protein interactions (PPIs) analysis highlighted the novel association between the C677T MTHFR genotype and Vitamin D binding protein (DBP), which was confirmed by a molecular genetic analysis. The results suggested that the phenotype of the MTHFR might be associated with multiple proteins that have a synergistic effect, which might be related to the mechanism of ischemic stroke.
| S-EPMC5645471 | biostudies-literature
Project description:Background and purposeElevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels-associated genetic variant MTHFR C677T for association with magnetic resonance imaging-confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes.MethodsWe included 1359 magnetic resonance imaging-confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status.ResultsMTHFR C677T was associated with lacunar stroke (P=0.0003) and white matter hyperintensity volume (P=0.04), but not with the other stroke subtypes. Stratifying the lacunar stroke cases for hypertension status confirmed this association in hypertensive individuals (P=0.0002), but not in normotensive individuals (P=0.30).ConclusionsMTHFR C677T was associated with magnetic resonance imaging-confirmed lacunar stroke, but not large artery or cardioembolic stroke. The association may act through increased susceptibility to, or interaction with, high blood pressure. This heterogeneity of association might explain the lack of effect of lowering homocysteine in secondary prevention trials which included all strokes.
| S-EPMC4760380 | biostudies-literature
Project description:ObjectivesTo check for the association of genetic polymorphisms related to the methylenetetrahydrofolate reductase (MTHFR) gene namely C677T and A1298C with hypertension in Saudi affected subjects from Qassim region.Subjects and methodsParticipants included 123 Saudi hypertensive cases (83 males and 40 females) in addition to 250 (142 males and 108 females) unrelated healthy controls from the same locality. Their age mean ±SD was 50.93 ± 15.43 years. For all subjects, DNA was extracted followed by real-time PCR amplifications for characterization of genotypes and alleles related to MTHFR C677T and A1298C gene polymorphismsResultsTotal cases showed significantly higher carriage rate for the mutant allele 677T compared to controls (40.7% vs. 26%, OR=1.9, 95% CI= 1.2-3.1) with a lower frequency of the wild type 677CC genotype (59.3% vs. 74%, p=0.004). The same was observed among cases-subgroups of hypertension associated with obesity with a notably higher odds ratio (OR=2.6, 95% CI=1.3-5.01, p=0.004). Total cases showed also significantly higher frequency of mutant 1298 C allele carriage rate compared to controls (59.3% vs. 42.4%, OR=1.98, 95% CI= 1.3-3.1) with a lower frequency of the normal AA genotype (40.7% vs. 57.6%, p=0.003). The same was observed among cases-subgroups of hypertension associated with both diabetes and obesity and among cases of hypertension with obesity, also with higher odds ratio (OR=2.6 and 2.2 respectively).ConclusionThis work showed that genetic polymorphisms related to the MTHFR gene are associated with the risk of hypertension particularly when accompanied with obesity and diabetes among Saudi subjects.
| S-EPMC3523778 | biostudies-literature
Project description:Navigation skills deteriorate with age, but the mechanisms of the decline are poorly understood. Part of the decrement may be due to age-related vascular risk factors. The T allele in a C677T variant in methylenetetrahydrofolate reductase (MTHFR) gene is associated with elevated plasma homocysteine, which is detrimental to vascular integrity and has been linked to cognitive decline. We inquired if a combination of physiological (hypertension) and genetic (MTHFR 677T) vascular risks has a synergistic negative impact on cognitive performance in otherwise healthy adults. We tested 160 participants (18-80 years old) on a virtual water maze. Advanced age, female sex, and hypertension were associated with poorer performance. However, hypertensive carriers of the T allele performed significantly worse than the rest of the participants at all ages. These findings indicate that hypertension combined with a genetic vascular risk factor may significantly increase risk for cognitive impairment.
| S-EPMC2685204 | biostudies-literature
Project description:PurposeThis study aims to investigate the association between paternal methylenetetrahydrofolate reductase (MTHFR) polymorphisms (C677T) and embryonic development, pregnancy, and neonatal outcomes in intracytoplasmic sperm injection (ICSI) treatment.MethodsA total of 191 infertile men undergoing ICSI treatment at the Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, were recruited between January 2020 and June 2021. The MTHFR C677T polymorphism genotyping was evaluated in these male patients, and they were stratified into three groups according to genotyping results: Control (CC), heterozygote mutated (CT), and mutated homozygote (TT). In addition, we conducted a comparative analysis of embryonic development, pregnancy, and neonatal outcomes among these three groups.ResultsThe embryonic development (including normal fertilization rate (80.14% vs. 83.06% vs. 85.10%; p = 0.37), high-quality embryo rate (45.26% vs. 43.69% vs. 46.04%; p = 0.72), blastocyst formation rate (42.47% vs. 43.18% vs. 39.38%; p = 0.62), implantation rate (42.47% vs. 36.25% vs. 41.22%; p = 0.62), and clinical pregnancy rate (64.71% vs. 58.75% vs. 66.67%; p = 0.59) were not comparable among these three groups. Moreover, no significant difference was observed in terms of pregnancy outcomes (including miscarriage rate (24.24% vs. 12.77% vs. 22.5%; p = 0.35) and live birth rate (49.02% vs. 51.25% vs. 51.66%; p = 0.96)). Additionally, no marked difference was observed in terms of neonatal outcome (including, preterm delivery rate (24% vs. 14.63% vs. 9.67%; p = 0.35), birth height (p = 0.75), birth weight (p = 0.35), neonatal sex (p = 0.48), gestational age at delivery (p = 0.24), Apgar score (p = 0.34), and birth defects (0% vs. 2% vs. 9%; p = 0.23) among the study groups.ConclusionThe paternal MTHFR C677T polymorphism is not associated with embryo quality, pregnancy, or neonatal outcomes in ICSI treatment. Therefore, in our population, MTHFR polymorphisms do not provide helpful information in explaining ICSI failure.
| S-EPMC9816894 | biostudies-literature
Project description:Previous studies have shown that the single nucleotide polymorphisms (SNPs) in Methylenetetrahydrofolate reductase (MTHFR) and Glutathione S-transferases (GSTs, including GSTM1, GSTT1) genes play an important role in determining the response of an individual to environmental pathogenesis and significantly relate to incidences of various human tumors, including brain tumors. However, these genes' polymorphisms on meningioma risk remains poorly understood. The relevant inferences from previous studies are hindered by their limited statistical power and conflicting results. The aim of this meta-analysis is to provide a relatively comprehensive account of the association between these polymorphisms and human meningioma risk. A literature search for eligible studies published before January 1, 2014 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CNKI databases. Pooled odds ratios (OR) with their corresponding 95% confidence intervals (95% CI) were used to evaluate the strength of the association under a fixed or random effect model according to heterogeneity test results. Heterogeneity and publication bias were evaluated. All statistical analyses were conducted by using the software of STATA 12.0 (STATA Corporation, College Station, TX, USA). For MTHFR C677T (dbSNP: rs1801133) (C T) polymorphism, 9 individual case-control studies from six publications with 1,615 cases and 1,909 controls were obtained. For GSTM1 null polymorphism, there were 4 studies with 417 cases and 1,735 controls. For GSTT1 null polymorphism, there were 4 studies with 405 cases and 1,622 controls. The combined results for the MTHFR C677T show that carriers of the CT genotype may be associated with a higher meningioma risk (OR = 1.20, 95% CI 1.05-1.38, P = 0.009). Stratified analyses show that Caucasians have significantly higher risk if they carry the CT genotype of MTHFR (OR = 1.31, 95% CI 1.05-1.63, P = 0.02). Risk of Caucasians carrying TT + CT genotype is also significantly higher (OR = 1.27, 95% CI 1.02-1.58, P = 0.03). Risk of Caucasians carrying TT genotype is not significantly different compared to control population (OR = 0.96, 95% CI 0.69-1.34, P = 0.82). All of the enrolled studies about GSTM1/GSTT1 are on Caucasians. The pooled ORGSTM1 and ORGSTT1 were not significant in Caucasian population. These results indicate SNPs of MTHFR C677T are related to meningioma risk with ethnic differences. Caucasians carrying CT genotype of MTHFR C677T have significantly higher meningioma susceptibility. SNPs of GSTM1/GSTT1 are not related to meningioma risk.
| S-EPMC4276156 | biostudies-literature
Project description: Not available
| S-EPMC9828550 | biostudies-literature
Project description:ObjectiveTo examine the relationship between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and susceptibility to lung cancer in a female Chinese population.MethodA hospital-based case-control study of 388 cases and 388 controls was conducted. Two polymorphisms in MTHFR were detected using TaqMan methods.ResultsThe MTHFR C677T polymorphism was associated with the risk of lung cancer and lung adenocarcinoma. Carriers with the TT genotype of C677T were observed to have an increased risk of lung cancer and lung adenocarcinoma (the ORs were 1.550 and 1.588, respectively). By contrast, the A1298C polymorphism had a negative relationship with the risk of lung cancer and lung adenocarcinoma; compared with the AA genotype carriers, the CC genotype carriers had a lower risk of lung cancer and adenocarcinoma in the female Chinese population (ORs were 0.302 and 0.215, respectively). In the stratified analyses, we observed only the A1298C polymorphism in the CC genotype carriers with a statistically significant reduction in the risk of non-small-cell lung cancer, compared to the AA genotype carriers. No significant statistical association was found between the MTHFR gene polymorphisms and risk of the residual subtype of lung cancer.ConclusionThis study provides evidence that the MTHFR C677T polymorphism may contribute to the development of lung cancer and lung adenocarcinoma in a female Chinese population. However, the MTHFR A1298C polymorphism may be associated with the decreasing risk of lung cancer.
| S-EPMC6175546 | biostudies-literature
Project description:Fluoropyrimidines are the backbone of chemotherapy regimes used to treat metastatic colorectal cancer (CRC). These drugs act in different pathways of folate metabolism altering DNA synthesis mainly by inhibition of the tymidylate synthase. For this reaction the 5,10-methylenetetrahydrofolate acts as cofactor. It has been demonstrated that A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene result in reduced enzyme activity that leads to reduced availability of this important cofactor. Hence, we hypothesized that the presence of these polymorphisms are related to the efficacy and toxicity of fluoropyrimidines in patients with CRC.
| 2298058 | ecrin-mdr-crc