scholarly journals Association Between MTHFR Polymorphisms and the Risk of Essential Hypertension: An Updated Meta-analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Meng ◽  
Shaoyan Huang ◽  
Yali Yang ◽  
Xiaofeng He ◽  
Liping Fei ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Essential Hypertension ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Cochrane Library ◽  
Mthfr Polymorphisms ◽  
Southeast Asians ◽  
Increased Risk ◽  
Meta Analyses

Background: Since the 1990s, there have been a lot of research on single-nucleotide polymorphism (SNP) and different diseases, including many studies on 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and essential hypertension (EH). Nevertheless, their conclusions were controversial. So far, six previous meta-analyses discussed the internal relationship between the MTHFR polymorphism and EH, respectively. However, they did not evaluate the credibility of the positive associations. To build on previous meta-analyses, we updated the literature by including previously included papers as well as nine new articles, improved the inclusion criteria by also considering the quality of the papers, and applied new statistical techniques to assess the observed associations. Objectives: This study aims to explore the degree of risk correlation between two MTHFR polymorphisms and EH. Methods: PubMed, EMBASE, the Cochrane Library, CNKI, and Wan Fang electronic databases were searched to identify relevant studies. We evaluated the relation between the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms and EH by calculating the odds ratios (OR) as well as 95% confidence intervals (CI). Here we used subgroup analysis, sensitivity analysis, cumulative meta-analysis, assessment of publication bias, meta-regression meta, False-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and Venice criterion. Results: Overall, harboring the variant of MTHFR C677T was associated with an increased risk of EH in the overall populations, East Asians, Southeast Asians, South Asians, Caucasians/Europeans, and Africans. After the sensitivity analysis, positive results were found only in the overall population (TT vs. CC: OR = 1.14, 95% CI: 1.00–1.30, Ph = 0.032, I2 = 39.8%; TT + TC vs. CC: OR = 1.15, 95% CI: 1.01–1.29, Ph = 0.040, I2 = 38.1%; T vs. C: OR = 1.14, 95% CI: 1.04–1.25, Ph = 0.005, I2 = 50.2%) and Asian population (TC vs. CC: OR = 1.14, 95% CI: 1.01–1.28, Ph = 0.265, I2 = 16.8%; TT + TC vs. CC: OR = 1.17, 95% CI: 1.04–1.30, Ph = 0.105, I2 = 32.9%; T vs. C: OR = 1.10, 95% CI: 1.02–1.19, Ph = 0.018, I2 = 48.6%). However, after further statistical assessment by FPRP, BFDP, and Venice criteria, the positive associations reported here could be deemed to be false-positives and present only weak evidence for a causal relationship. In addition, when we performed pooled analysis and sensitivity analysis on MTHFR A1298C; all the results were negative. Conclusion: The positive relationships between MTHFR C677T and A1298C polymorphisms with the susceptibility to present with hypertension were not robust enough to withstand statistical interrogation by FPRP, BFDP, and Venice criteria. Therefore, these SNPs are probably not important in EH etiology.

scholarly journals The association of MTHFR C677T variant with increased risk of ischemic stroke in the elderly population: a meta-analysis of observational studies

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Guilin Chang ◽  
Zheng Kuai ◽  
Jia Wang ◽  
Jiayu Wu ◽  
Kan Xu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Elderly Population ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
The Elderly ◽  
Cochrane Library ◽  
Case Control Studies ◽  
Eligibility Criteria ◽  
Increased Risk

Abstract Background C677T point mutation in methylenetetrahydrofolate reductase (MTHFR) gene have been found to be associated with ischemic stroke in general population, while the results seem inconsistent. We aim to assess the association between variant MTHFR C677T variant and increased risk of ischemic stroke and focus on the elderly population. Methods We searched PubMed, Embase, Cochrane Library, and Web of Science for eligible studies. Odds ratios (ORs) were calculated with the two-tailed 95% confidence intervals (CIs) by using a random effects model to evaluate any possible association. Among the Chinese and non-Chinese populations, we conducted a subgroup analysis. Results The electronic database search yielded 1,358 citations as of December 2017; finally, nine case-control studies involving 3,337 subjects fulfilled our eligibility criteria for inclusion in the study. The pooled results showed that MTHFR C677T variant increased the risk of ischemic stroke (OR = 1.23, 95%CI 1.06–1.43, P = 0.0067 for CT + TT vs. CC; OR = 1.18, 95%CI 1.01–1.38, P = 0.0333 for CT vs. CC; OR = 1.41, 95%CI 1.14–1.75, P = 0.0016 for TT vs. CC; OR = 1.27, 95%CI 1.05–1.54, P = 0.0145 for TT vs. CC + CT; OR = 1.18, 95%CI 1.06–1.31, P = 0.0023 for T-allele vs. C-allele). Further subgroup analyses in the Chinese population indicated that MTHFR C677T variant was associated with a higher risk of ischemic stroke. Conclusion Our findings showed that T-allele increases risk for stroke in the pooled sample. This association was statistically significant in the Chinese cohorts and showed a similar trend in the non-Chinese cohorts. (Word count: 237).

scholarly journals Assessing the Association between the Methylenetetrahydrofolate Reductase (MTHFR) 677C->T Polymorphism on Blood Folate Concentrations: A Systematic Review and Meta-analysis of Trials and Observational Studies

2015 ◽  
pp. 650-651
Author(s):  
Becky Tsang ◽  
Amy Cordero ◽  
Claire Marchetta ◽  
Joseph Mulinare ◽  
Patricia Mersereau ◽  
...  
Keyword(s):  
Systematic Review ◽  
Protein Binding ◽  
Observational Studies ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Review Of Literature ◽  
Binding Assays ◽  
Lower Blood ◽  
Meta Analyses

Objectives: The methylenetetrahydrofolate reductase (MTHFR) 677C->T polymorphism is a risk factor for neural tube birth defects (NTDs). The T allele produces an enzyme with reduced folate processing capacity, which has been shown to produce lower blood folate concentrations in some studies. Our objective was to assess the association between MTHFR C677T genotypes (CC, CT, TT) and blood folate concentrations among women aged 12-49 years. Methods: We conducted a systematic review of literature published between 1/1992-7/2013 to identify controlled trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We applied a Bayesian random-effects model to predict differences in blood folate concentrations between MTHFR C677T genotypes, stratified by folate assay. Results: Thirty-eight studies met criteria for inclusion. Serum/plasma folate concentrations showed a consistent genotype trend with the highest concentrations for CC (CC > CT > TT) regardless of assay type. RBC folate concentrations measured by microbiologic assay also demonstrated this trend; however, this trend was reversed (CC < CT < TT) in studies using protein-binding assays. Conclusions: Meta-analyses results showed blood folate concentrations differed by assay type and genotype. Previous evidence has shown that RBC folate concentrations measured with a radioimmunoassay requires adjustment for genotype-dependent folate recovery; our results suggest that other protein-binding assays could have similar limitations. Compared to CC individuals, TT individuals have lower blood folate concentrations, which may increase a woman's risk for an NTD-affected pregnancy.

scholarly journals Does Internet-based guided-self-help for depression cause harm? An individual participant data meta-analysis on deterioration rates and its moderators in randomized controlled trials

2016 ◽  
Vol 46 (13) ◽  
pp. 2679-2693 ◽  
Author(s):  
D. D. Ebert ◽  
L. Donkin ◽  
G. Andersson ◽  
G. Andrews ◽  
T. Berger ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Reliable Change Index ◽  
Cochrane Library ◽  
Pool Data ◽  
Negative Effects ◽  
Self Help ◽  
Increased Risk ◽  
Low Education ◽  
Individual Participant ◽  
Meta Analyses

BackgroundAlmost nothing is known about the potential negative effects of Internet-based psychological treatments for depression. This study aims at investigating deterioration and its moderators within randomized trials on Internet-based guided self-help for adult depression, using an individual patient data meta-analyses (IPDMA) approach.MethodStudies were identified through systematic searches (PubMed, PsycINFO, EMBASE, Cochrane Library). Deterioration in participants was defined as a significant symptom increase according to the reliable change index (i.e. 7.68 points in the CES-D; 7.63 points in the BDI). Two-step IPDMA procedures, with a random-effects model were used to pool data.ResultsA total of 18 studies (21 comparisons, 2079 participants) contributed data to the analysis. The risk for a reliable deterioration from baseline to post-treatment was significantly lower in the intervention v. control conditions (3.36 v. 7.60; relative risk 0.47, 95% confidence interval 0.29–0.75). Education moderated effects on deterioration, with patients with low education displaying a higher risk for deterioration than patients with higher education. Deterioration rates for patients with low education did not differ statistically significantly between intervention and control groups. The benefit–risk ratio for patients with low education indicated that 9.38 patients achieve a treatment response for each patient experiencing a symptom deterioration.ConclusionsInternet-based guided self-help is associated with a mean reduced risk for a symptom deterioration compared to controls. Treatment and symptom progress of patients with low education should be closely monitored, as some patients might face an increased risk for symptom deterioration. Future studies should examine predictors of deterioration in patients with low education.

scholarly journals Epidural-Related Fever and Maternal and Neonatal Morbidity: A Systematic Review and Meta-Analysis

Neonatology ◽  
2020 ◽  
Vol 117 (3) ◽  
pp. 259-270 ◽  
Author(s):  
Sophie Jansen ◽  
Enrico Lopriore ◽  
Christiana Naaktgeboren ◽  
Marieke Sueters ◽  
Jacqueline Limpens ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cohort Studies ◽  
Antibiotic Treatment ◽  
Assessment Tool ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Increased Risk ◽  
Observational Cohort ◽  
Meta Analyses ◽  
The Impact

<b><i>Background:</i></b> While epidural analgesia (EA) is associated with maternal fever during labor, the impact on the risk for maternal and/or neonatal sepsis is unknown. <b><i>Objectives:</i></b> The aim of this systematic review was to investigate the effect of epidural-related intrapartum fever on maternal and neonatal outcomes. <b><i>Methods:</i></b> OVID MEDLINE, OVID Embase, the Cochrane Library, Cochrane Controlled Register of Trials, and clinical trial registries were searched for randomized controlled trials (RCT) and observational cohort studies from inception to November 2018. A total of 761 studies were identified with 100 eligible for full-text review. Only articles investigating the relationship between EA and maternal fever during labor were eligible for inclusion. Study quality was assessed using the Cochrane’s Risk of Bias tool and National Institute of Health Quality Assessment Tool. Two meta-analyses – one each for the RCT and observational cohort groups – were performed using the random-effects model of Mantel-Haenszel to produce summary risk ratios (RR) with 95% CI. <b><i>Results:</i></b> Twelve RCTs and 16 observational cohort studies involving 579,157 parturients were included. RRs for maternal fever for the RCT and cohort analyses were 3.54 (95% CI 2.61–4.81) and 5.60 (95% CI 4.50–6.97), respectively. Meta-analyses of RR for maternal infection in both groups were infeasible given few occurrences. Meta-analysis of data from observational studies showed an increased risk for maternal antibiotic treatment in the epidural group (RR 2.60; 95% CI 1.31–5.17). For both analyses, neonates born to women with an epidural were not evaluated more often for suspected sepsis. Neither analysis reported an increased rate of neonatal bacteremia or neonatal antibiotic treatment after EA, although data precluded conclusiveness. <b><i>Conclusion:</i></b> EA increases the risk of intrapartum fever and maternal antibiotic treatment. However, a definite conclusion on whether EA increases the risk for a proven maternal and/or neonatal bacteremia cannot be drawn due to the low quality of data. Further research on whether epidural-related intrapartum fever is of infectious origin or not is therefore needed.

scholarly journals Association of MTHFR C677T and A1298C Polymorphisms with Susceptibility to Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Atefeh RAOUFI ◽  
Behdad RAHIMI KELARIJANI ◽  
Hamid Reza AHADI ◽  
Bahareh HASSANI DERAKHSHANDEH ◽  
Zahra NOOROOLLAHZADEH ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Gene Interaction ◽  
Lymphocytic Leukemia ◽  
Mthfr Polymorphism ◽  
Mthfr Polymorphisms ◽  
Comprehensive Search ◽  
Allelic Model

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.  

scholarly journals The methylenetetrahydrofolate reductase C677T genotype and the risk of obesity in three large population-based cohorts.

2008 ◽  
Vol 159 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Sarah J Lewis ◽  
Debbie A Lawlor ◽  
Børge G Nordestgaard ◽  
Anne Tybjærg-Hansen ◽  
Shah Ebrahim ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Causal Effect ◽  
Meta Analysis ◽  
Large Population ◽  
High Body Mass Index ◽  
Mthfr C677t ◽  
Health Study ◽  
Positive Finding ◽  
Central Adiposity ◽  
Increased Risk

ObjectiveEpidemiological studies have shown that low folate levels are associated with a high body mass index (BMI). These findings have potentially important health implications and warrant further investigation to determine whether a causal relationship exists and the direction of this relationship. The methylenetetrahydrofolate reductase (MTHFR)C677T TTgenotype is associated with reduced folate availability and may be a surrogate for measuring folate levels. We sought to determine whetherMTHFR C677Tgenotype was associated with obesity.DesignWe carried out our study on four populations from three longitudinal studies based in the UK and Denmark in which DNA for genotyping was obtained along with measures of obesity.MethodsOur subjects were taken from the British Women's Heart and Health Study (BWHHS), the Avon Longitudinal Study of Parents and Children (two populations: mothers and children) and the Copenhagen City Heart Study. We performed analyses separately by population, and then carried out a meta-analysis, combining similar populations.ResultsInitial findings in the BWHHS suggested that theTTgenotype may be associated with an increased risk of obesity BMI≥30, however, no association was found with BMI or central adiposity in this cohort. This genotype was not associated with obesity in our other cohorts.ConclusionsOur results suggest that the initial positive finding with obesity in the BWHHS was a chance finding. Our findings do not support a causal effect of low folate on obesity.

scholarly journals Associations between TLR4 Polymorphisms and Open Angle Glaucoma: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Zhongjing Lin ◽  
Shouyue Huang ◽  
Jun Sun ◽  
Bing Xie ◽  
Yisheng Zhong
Keyword(s):  
Genetic Model ◽  
Open Angle Glaucoma ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Recessive Model ◽  
Cochrane Library ◽  
Open Angle ◽  
Increased Risk ◽  
Meta Analyses ◽  
The Cochrane Library

Background. Previous studies exploring the association between toll-like receptor 4 (TLR4) polymorphisms and open angle glaucoma (OAG) presented inconsistent results. We aimed to investigate the association between TLR4 polymorphisms and OAG. Methods. A systematic literature search was conducted in PubMed, EMBASE, ISI Web of Knowledge, and the Cochrane Library up to 31 December 2018. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated, followed by stratification analyses according to ethnicity and glaucoma subtype. Results. TLR4 rs7037117 polymorphism had significant associations with increased risk of OAG in allelic model (OR=1.25; 95%CI: 1.09-1.44; P=0.002) and recessive model (OR=1.49; 95%CI: 1.08-2.04; P=0.01). With regard to rs10759930, rs12377632, and rs2149356, the results showed significant increased risks in all genetic models (all P<0.05), whereas, for rs1927914, rs11536889, and rs7045953, no significant associations were identified in any genetic model (all P>0.05). Furthermore, the association of rs1927911 with OAG risk was found to be significant in recessive model (OR=1.34; 95%CI: 1.06-1.71; P=0.02). As for rs4986790 and rs4986791, meta-analyses were not performed due to the limited number of studies and the ethnic differences. Subgroup analysis indicated that the above polymorphisms with significant differences might increase the susceptibility in POAG patients. As for the ethnicity, rs7037117, rs10759930, and rs1927911 might increase the risk in Asians, while rs12377632 and rs2149356 might increase the risk in Asians and Mexicans. Conclusion. The meta-analysis highlighted that certain mutations of some TLR4 polymorphisms might increase the susceptibility of OAG. However, TLR4 polymorphisms are still far from being candidate genetic biomarkers for OAG. Additional researches involving larger scale epidemiological studies are warranted to validate our results.

scholarly journals Meta-analysis of the relationship between methylenetetrahydrofolate reductase C677T and A1298C polymorphism and venous thromboembolism in the Caucasian and Asian

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Miao Gao ◽  
Na Feng ◽  
Meixia Zhang ◽  
Xinyu Ti ◽  
Xiuping Zuo
Keyword(s):  
Venous Thromboembolism ◽  
Methylenetetrahydrofolate Reductase ◽  
Genetic Model ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Cochrane Library ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Mthfr A1298c ◽  
A1298c Polymorphism

Abstract Recent years, it is a highly debated topic that whether methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and A1298C polymorphism could increase susceptibility to venous thromboembolism (VTE) in the Asian and Caucasian. Therefore, we expect to settle that controversy evidentially. Basic methods: Electronic databases (Pubmed, embase, Cochrane library, scopus, OvidSP, Wiley Online library, Springer link, EBSCO, Elsevier Science Direct, Google scholar) without date limitation were searched. Crude odds ratio (OR) along with 95% confidence interval (95% CI) was calculated to assess the association quantitatively. Finally, a total of 37 eligible studies were included, containing 31 for MTHFR C677T polymorphism and 6 for MTHFR A1298C polymorphism. The pooled results suggested that MTHFR C677T mutation may increase susceptibility to VTE in reverse recessive model (CC+CT vs TT): OR = 0.68 (0.56, 0.83), reverse dominant model (CC vs CT +TT): OR = 0.82 (0.72, 0.94), heterozygote model (CT vs TT): OR = 0.65 (0.52, 0.81), homozygote model (CC vs TT): OR = 0.73 (0.60, 0.89) and allele model (C vs T): OR = 0.80 (0.71, 0.90). Subgroup analysis about Asian also support that results, but Caucasian group not. In addition, MTHFR A1298C polymorphism may be not related to VTE in all genetic model. The results of meta-analysis indicated that MTHFR C677T polymorphism might increase the risk of VTE, especially in Asian population.

scholarly journals Does chronotherapy for essential hypertension matter by class? A systematic review and meta-analysis

2021 ◽  
Author(s):  
Hongyu Kuang ◽  
Yunlin Chen
Keyword(s):  
Essential Hypertension ◽  
Antihypertensive Drugs ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Great Decrease ◽  
Quantitative Review ◽  
Receptor Blockers ◽  
Meta Analyses ◽  
The Cochrane Library ◽  
Review Manager

Objectives The study was performed to evaluate the efficacy and safety of chronotherapy of hypertension with different medications monotherapy or a combination compared with traditional regimens Methods Three databases including PubMed, EMBASE and the Cochrane Library were searched, from the inception of each database to 10 April 2020. The Review Manager 5.4 was adopted for meta-analyses and subgroup analyses. The blood pressure delta (Δ) was used as mean of differences (MD) with 95% confidence intervals (CIs), and the estimated effect for events estimates the 95% CIs for frequency of events. The adults with essential hypertension were treated with chronotherapy and traditional regimens. Results Twenty-eight RCTs, recruiting 1865 patients in bedtime/evening dosing and 1867 in awakening/morning dosing, were enrolled in this quantitative review. Meta-analysis showed no significant differences for overall drug-related AEs (RR=0.81, P=0.17; I2=41%), but an obvious reduction of risk for overall withdrawals (RR=0.52, P=0.005; I2=0.0%) with bedtime dosing. No statistically significant differences were noted for clinic BP and diurnal BP, but 24-hour (48-hour) BP, nocturnal BP, morning BP, and non-dippers (%) showed obvious reductions, statistically. By class, there existed different efficacy between 2 administrations, with great decrease in nocturnal BP control and changes in circadian rhythm with RAAS blockers monotherapy, but an all-day control of BP for CCBs and diuretics. With regard to a combination, no significant differences in BP management were detected and the data about beta-receptor blockers were limited. Conclusions The safety and efficacy of chronotherapy in antihypertensive drugs might be based on the classes.

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