MTHFR Polymorphism Is Associated With Severe Methotrexate-Induced Toxicity in Osteosarcoma Treatment

BackgroundPrevious studies have revealed the critical role of methylene tetrahydrofolate reductase (MTHFR) polymorphisms in response to high-dose methotrexate (MTX)-induced toxicity in osteosarcoma patients. However, the conclusions remain controversial. In this setting, we performed a meta-analysis to determine their association more precisely.MethodEligible studies were searched and screened in PubMed, Web of Science, Cochrane Library, Clinical-Trials.gov, Embase, and China National Knowledge Infrastructure (CNKI) following specific inclusion and exclusion criteria. The required information was retrieved and collected for subsequent meta-analysis. Association between MTHFR polymorphism and MTX toxicity was evaluated by odds ratios (ORs).ResultsSeven studies containing 585 patients were enrolled and analyzed in this meta-analysis. Overall, the MTX related grade 3-4 liver toxicity was significantly associated with MTHFR rs1801133 allele (T vs. C: OR=1.61, 95%CI=1.07-2.42, P=0.024), homozygote (TT vs. CC: OR=2.11, 95%CI=1.06-4.21, P=0.011), and dominant genetic model (TT/TC vs. CC: OR=3.15, 95%CI=1.30-7.60, P=0.035) in Asian population. Meanwhile, close associations between MTX mediated grade 3-4 mucositis and MTHFR rs1801133 polymorphism were identified in allele contrast (T vs. C: OR=2.28, 95%CI=1.49-3.50, P<0.001), homozygote comparison (TT vs. CC: OR=4.07, 95%CI=1.76-9.38, P=0.001), heterozygote comparison (TC vs. CC: OR=2.55, 95%CI=1.20-5.42, P=0.015), recessive genetic model (TT vs. TC/CC: OR=2.09, 95%CI=1.19-3.67, P=0.010), and dominant genetic model (TT/TC vs. CC: OR=2.97, 95%CI=1.48-5.96, P=0.002). Additionally, kidney toxicity was corelated with the heterozygote comparison (TC vs. CC: OR=2.63, 95%CI=1.31-5.29, P=0.007) of rs1801133 polymorphism.ConclusionThe MTHFR rs1801133 polymorphism was significantly associated with severer liver toxicity induced by high-dose MTX treatment in the Asian population. In the meantime, patients with MTHFR rs1801133 polymorphism were predisposed to MTX- related mucositis.

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MTHFR A1298C gene polymorphism on stroke risk: an updated meta-analysis

Genes and Environment ◽

10.1186/s41021-021-00208-z ◽

2021 ◽

Vol 43 (1) ◽

Author(s):

Xiaobo Dong ◽

Jun Wang ◽

Gesheng Wang ◽

Jiayue Wang ◽

Lei Wang ◽

...

Keyword(s):

Gene Polymorphism ◽

Stroke Risk ◽

Genetic Model ◽

Meta Analysis ◽

Cochrane Library ◽

China National Knowledge Infrastructure ◽

Knowledge Infrastructure ◽

Potential Association ◽

Dominant Genetic Model ◽

Stroke Type

Abstract Background Previous studies have shown the effect of MTHFR A1298C gene polymorphism on stroke risk. But the results of published studies remained inconclusive and controversial. So we conducted a meta-analysis to accurately estimate the potential association between MTHFR A1298C gene polymorphism and stroke susceptibility. Methods A systematic literature search on Embase, Pubmed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) and WanFang electronic database identified 40 articles including 5725 cases and 8655 controls. Strength of association was evaluated by pooled odds ratio (OR), 95% confidence interval (CI) and p value. Funnel plots and Begger’s regression test were applied for testing the publication bias. Statistical analysis of all data was performed by Stata 12.0. Results The meta-analysis results indicated a significant relationship between MTHFR gene A1298C polymorphisms and stoke risk under the C allelic genetic model (OR = 1.19, 95%CI = 1.07–1.32, p = 0.001), dominant genetic model (OR = 1.19, 95%CI = 1.06–1.33, p = 0.004) and recessive genetic model (OR = 1.43, 95%CI =1.15–1.77, p = 0.001). In subgroup analysis, we discovered obvious correlation in three genetic model of Asian, stroke type, adult by ethnicity, population, stroke type, source of control and case size. Additionally, in studies of control from hospital and case size equal 100, obvious correlation was also found in the three genetic model. Conclusions Our meta-analysis results indicated that there was evidence to support the correlation between MTHFR A1298C polymorphism and stroke susceptibility, especially in adults and ischemic stroke.

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Association of Rs13118928 and Rs1828591 Polymorphisms in HHIP Gene with COPD Susceptibility: A Meta-Analysis of Case-Control Studies

10.21203/rs.3.rs-1150373/v1 ◽

2022 ◽

Author(s):

Xue-mei Wei ◽

Xiao-hong Yang

Keyword(s):

Genetic Model ◽

Meta Analysis ◽

Susceptibility Gene ◽

Cochrane Library ◽

Chronic Obstructive ◽

Case Control Studies ◽

Interacting Protein ◽

Online Databases ◽

Dominant Genetic Model ◽

Newcastle Ottawa Scale

Abstract In recent years, investigators have been striving to explore the pathogenesis of chronic obstructive pneumonia disease (COPD). Hedgehog Interacting Protein (HHIP) has been identified as a candidate susceptibility gene. Our aim is to synthesize and include all evidences to get a more comprehensive result. We searched 6 online databases- PubMed, Web of Science, Cochrane Library, Wanfang, EMBASE, CNKI. All included studies were published before October 1, 2021. We used Newcastle-Ottawa scale (NOS) to evaluate the bias of each study. Meta-analysis methods were conducted to evaluate the pooled result. A total of 14 comparative studies were included in this meta-analysis, for rs13118928 polymorphism, significant associations were observed in 5 genetic models, (A vs. G, OR=1.18, 95CI%=[1.07-1.30], P=0.0006; AA vs. GG, OR=1.56, 95CI%=[1.22-2.00], P=0.0004; AG vs. GG, OR=1.28, 95CI%=[1.05-1.55], P=0.01; AA+AG vs. GG, OR=1.36, 95CI%=[1.12-1.65], P=0.002; AA vs. AG+GG, OR=1.18, 95CI%=[1.05-1.33], P=0.006). as for rs1828591, there were also significant associations detected in the overall population, (A vs. G, OR=1.12, 95CI%=[1.05-1.19], P=0.0003; AA vs. GG, OR=1.27, 95CI%=[1.04-1.56], P=0.02; AG vs. GG, OR=1.25, 95CI%=[1.03-1.51], P=0.02; AA+AG vs. GG, OR=1.26, 95CI%=[1.04-1.53], P=0.02; AA vs. AG+GG, OR=1.10, 95CI%=[1.01-1.19], P=0.03). This meta-analysis showed that the A allele in both rs13118928 and rs1828591 was turn out to be the risk allele in developing COPD. The result of Codominant genetic model, Dominant genetic model and Recessive genetic model remain the same.

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Angiotensinogen M235T polymorphism and susceptibility to hypertrophic cardiomyopathy in Asian population: A meta analysis

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320320978100 ◽

2020 ◽

Vol 21 (4) ◽

pp. 147032032097810

Author(s):

Zhen Zhen ◽

Lu Gao ◽

Qin Wang ◽

Xi Chen ◽

Jia Na ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Genetic Model ◽

Meta Analysis ◽

Asian Population ◽

Genetic Models ◽

The Other ◽

Familial Hypertrophic Cardiomyopathy ◽

Cochrane Library ◽

Newcastle Ottawa Scale ◽

M235t Polymorphism

Objective: To explore the relationship between the polymorphism of angiotensinogen gene (AGT) M235T and susceptibility to hypertrophic cardiomyopathy (HCM) in Asian population by meta-analysis. Methods: PubMed, Embase, Web of Science, Cochrane library, CNKI, Wan Fang, and other databases were searched to collect the literature about AGT M235T polymorphism and HCM from the inception to March 1, 2020. The Newcastle-Ottawa Scale (NOS) checklist was uesd to perform independent literature review and study quality assessment. Data was analyzed by Stata 15.0 software. Results: The results showed that, except for the recessive genetic model (TT vs MT+MM: OR = 1.27, 95%CI: 1.05–1.53), in the other four genetic models, the M235T polymorphism had no significant correlation with the risk of HCM (T vs M: OR = 1.17, 95%CI: 0.88–1.57; TT+MT vs MM: OR = 1.13, 95%CI: 0.55–2.33; TT vs MM: OR = 1.25, 95%CI: 0.60–2.59; TM vs MM: OR = 0.95, 95%CI0.5–1.82). The results of subgroup analysis showed that, except for the heterozygous genetic model, in the other four genetic models, M235T polymorphism was significantly associated with sporadic hypertrophic cardiomyopathy (SHCM), but not with familial hypertrophic cardiomyopathy (FHCM) ( p > 0.05). Conclusion: M235T polymorphism in Asians is associated with HCM, especially SHCM. Heterozygotes increase the risk of patients with SHCM.

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The Safety and Efficacy Evaluation of Dexmedetomidine for Procedural Sedation and Postoperative Behaviors in Pediatric Populations: A Systematic Review and Meta-analysis

Annals of Pharmacotherapy ◽

10.1177/10600280211009845 ◽

2021 ◽

pp. 106002802110098

Author(s):

Linguang Gan ◽

Xiaohong Zhao ◽

Xiangjian Chen

Keyword(s):

Pediatric Population ◽

Meta Analysis ◽

Procedural Sedation ◽

Cochrane Library ◽

Control Group ◽

High Dose ◽

Efficacy Evaluation ◽

Safety And Efficacy ◽

Ovid Medline ◽

Pediatric Populations

Background: This study systematically evaluated the safety and efficacy of dexmedetomidine for procedural sedation and postoperative behaviors in a pediatric population as well as whether the results met the information required to draw conclusions. Objective: To evaluate the safety and efficacy evaluation of dexmedetomidine for procedural sedation and postoperative behaviors in a pediatric population. Methods: PubMed, Cochrane library, Web of Science and Ovid MEDLINE were searched to obtain randomized controlled trials (RCTs) comparing dexmedetomidine with control medicine and comparing different doses of dexmedetomidine. Results: There were a total of 16 RCTs for a total of 3240 patients. Dexmedetomidine slowed down the heart rate (HR; mean difference: −13.27; 95% CI: −16.41 to 10.14; P < 0.001) and reduced postoperative delirium (risk ratio [RR]: 0.31; 95% CI: 0.20-0.50; P < 0.001), the number of pain patients (RR: 0.48; 95% CI: 0.30-0.75; P = 0.002), and desaturation (RR: 0.34; 95% CI: 0.13-0.89; P = 0.03) compared with the control group. The limitation was that it was difficult to determine the range of low- and high-dose dexmedetomidine. Conclusion and Relevance: Dexmedetomidine slowed down intraoperative HR within the normal range, which might reduce myocardial oxygen consumption. It reduced postoperative pain and postoperative complications: delirium and desaturation. Dexmedetomidine showed no dose-dependent increase in the procedural sedation time of pediatric patients. Clinically, dexmedetomidine can improve pediatric procedural sedation and postoperative behavior, and it can be considered as a related medicine for safety in pediatric surgery.

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Combination Therapy with an SGLT2 Inhibitor as Initial Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm8010045 ◽

2019 ◽

Vol 8 (1) ◽

pp. 45 ◽

Cited By ~ 17

Author(s):

Tamara Y. Milder ◽

Sophie L. Stocker ◽

Christina Abdel Shaheed ◽

Lucy McGrath-Cadell ◽

Dorit Samocha-Bonet ◽

...

Keyword(s):

Type 2 Diabetes ◽

Combination Therapy ◽

Low Dose ◽

Meta Analysis ◽

Sglt2 Inhibitor ◽

Cochrane Library ◽

High Dose ◽

Dose Combination ◽

Inhibitor Combination

Background: Guidelines differ with regard to indications for initial combination pharmacotherapy for type 2 diabetes. Aims: To compare the efficacy and safety of (i) sodium-glucose cotransporter 2 (SGLT2) inhibitor combination therapy in treatment-naïve type 2 diabetes adults; (ii) initial high and low dose SGLT2 inhibitor combination therapy. Methods: PubMed, Embase and Cochrane Library were searched for randomised controlled trials (RCTs) of initial SGLT2 combination therapy. Mean difference (MD) for changes from baseline (HbA1c, weight, blood pressure) after 24–26 weeks of treatment and relative risks (RR, safety) were calculated using a random-effects model. Risk of bias and quality of evidence was assessed. Results: In 4 RCTs (n = 3749) there was moderate quality evidence that SGLT2 inhibitor/metformin combination therapy resulted in a greater reduction in HbA1c (MD (95% CI); −0.55% (−0.67, −0.43)) and weight (−2.00 kg (−2.34, −1.66)) compared with metformin monotherapy, and a greater reduction in HbA1c (−0.59% (−0.72, −0.46)) and weight (−0.57 kg (−0.89, −0.25)) compared with SGLT2 inhibitor monotherapy. The high dose SGLT2 inhibitor/metformin combination resulted in a similar HbA1c but greater weight reduction; −0.47 kg (−0.88, −0.06) than the low dose combination therapy. The RR of genital infection with combination therapy was 2.22 (95% CI 1.33, 3.72) and 0.69 (95% CI 0.50, 0.96) compared with metformin and SGLT2 inhibitor monotherapy, respectively. The RR of diarrhoea was 2.23 (95% CI 1.46, 3.40) with combination therapy compared with SGLT2 inhibitor monotherapy. Conclusions: Initial SGLT2 inhibitor/metformin combination therapy has glycaemic and weight benefits compared with either agent alone and appears relatively safe. High dose SGLT2 inhibitor/metformin combination therapy appears to have modest weight, but no glycaemic benefits compared with the low dose combination therapy.

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Association Between Glucocorticoids Treatment and Viral Clearance Delay in Patients with COVID-19: A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-138544/v1 ◽

2021 ◽

Author(s):

Jianbo Li ◽

Xuelian Liao ◽

Yue Zhou ◽

Luping Wang ◽

Hang Yang ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Severity Of Illness ◽

Viral Clearance ◽

Cochrane Library ◽

High Dose ◽

Hazard Ratios ◽

Subgroup Analyses ◽

High Doses ◽

Critical Ill

Abstract BackgroundEvidence of glucocorticoids on viral clearance delay of COVID-19 patients is not clear. MethodsIn this systematic review and meta-analysis, we searched studies on Medline, Embase, EBSCO, ScienceDirect, Web of Science, Cochrane Library, and ClinicalTrials.gov from 2002 to December 2, 2020. We mainly pooled the adjusted hazard ratios (HRs), mean difference (MD) or risk ratios (RRs) of viral clearance delay and did subgroup analyses by doses and the severity of illness.ResultsOne trial and 38 observational studies, with a total of 7119 patients, were identified. Glucocorticoids treatment was associated with delayed viral clearance in COVID-19 (Adjusted HR 1.71, 95% CI 1.51 to 1.94, I2=22%, PI 1.45 to 2.01), based on moderate-quality evidence. In subgroup analyses, risk of viral clearance delay was significantly higher among COVID-19 patients being mild or moderate ill (adjusted HR 1.94, 95% CI 1.39 to 2.70, I2=52%; MD 2.59, 95% CI 1.21 to 3.97, I2=24%), but not in those of being severe or critical ill (adjusted HR 1.85, 95% CI 1.05 to 3.26; MD 0.22, 95% CI -1.85 to 2.29, I2=56%); taking high doses (adjusted HR 1.49, 95% CI 1.03 to 2.15; unadjusted RR 1.47, 95% CI 1.12 to 1.94) rather taking low doses (adjusted HR 1.39, 95% CI 0.93 to 2.08; unadjusted RR 1.33, 95% CI 1.00 to 1.77) or pulse (unadjusted RR 1.85, 95% CI 0.66 to 5.19).ConclusionsGlucocorticoids treatment delayed viral clearance in COVID-19 patients of being mild or moderate ill or taking a high dose, rather in those of being severe or critical ill or taking low dose or pulse.

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Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis

Journal of International Medical Research ◽

10.1177/03000605211038135 ◽

2021 ◽

Vol 49 (8) ◽

pp. 030006052110381

Author(s):

Yin Wang ◽

Yanqing Li ◽

Ye Chai

Keyword(s):

Multiple Myeloma ◽

Meta Analysis ◽

Complete Response ◽

Library Science ◽

Cochrane Library ◽

Control Group ◽

Efficacy And Safety ◽

Risk Patients ◽

Grade 3 ◽

Combination Regimens

Objective To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). Methods A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab. Results A total of seven RCTs were included ( n = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group. Conclusion The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.

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Poly(ADP-Ribose) Polymerase Inhibitors (PARPi) for Patients With Advanced Breast Cancer: a Meta-analysis of Randomized Controlled Trials

10.21203/rs.3.rs-48500/v1 ◽

2020 ◽

Author(s):

YongCheng Su ◽

XiaoGang Zheng

Keyword(s):

Breast Cancer ◽

Randomized Controlled Trials ◽

Fixed Effects ◽

Meta Analysis ◽

Parp Inhibitors ◽

Cochrane Library ◽

Controlled Trials ◽

Randomized Controlled ◽

Increased Risk ◽

Grade 3

Abstract BACKGROUND: Poly(ADP–ribose) polymerase (PARP) inhibitors are new class of drugs that are currently being studied in several malignancies. However, datas about the efficacy and safety of the PARP inhibitors are limited. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) in patients with breast cancer.METHODS: Pubmed/Medline, Embase, Cochrane Library, and abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) were searched for articles published from 2000 to June 2018.Summary incidences and the RR, HR with 95% confidence intervals, were calculated by using a random-effects or fixed-effects model.RESULTS: The summary HR indicated PARPi was not associated with OS (HR=0.83, 95%CI 0.66–1.06, Z=1.49, P=0.14), while it could significantly improve PFS ande time to deterioration (TTD) of global health status/quality of life(GHS/QoL) as compared with traditional standard therapy, the HR was 0.60(95%CI 0.50-0.72; Z=5.52, P＜0.00001) and 0.4 (95%CI 0.29–0.54,z=5.80 ,p=0.000),respectively.The RR of grade 3 or more anemia ,fatigue and headache was 3.02 (95% CI, 0.69–13.17;p = 0.14,,I2=90%),0.77 (95%CI, 0.34–1.73;p=0.52,I2=7%) and 1.13 (95% CI,0.30–4.18;p=0.86,I2=0%),respectively.CONCLUSION: The findings of this meta-analysis showed that PARPi has no significant effect on OS, while it could significantly improve in PFS and TTD of GHS/QoL for patients with advanced or metastatic breast cancer.Furthermore,our findings also demonstrated that the PARPi treatment is connected with an increased risk of grade 3 or more anemia adverse events.

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Association Between Glucocorticoids Treatment and Viral Clearance Delay in Patients with COVID-19: A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-138544/v2 ◽

2021 ◽

Author(s):

Jianbo Li ◽

Xuelian Liao ◽

Yue Zhou ◽

Luping Wang ◽

Hang Yang ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Severity Of Illness ◽

Viral Clearance ◽

Cochrane Library ◽

High Dose ◽

Hazard Ratios ◽

Subgroup Analyses ◽

High Doses ◽

Critical Ill

Abstract Background Evidence of glucocorticoids on viral clearance delay of COVID-19 patients is not clear. Methods In this systematic review and meta-analysis, we searched studies on Medline, Embase, EBSCO, ScienceDirect, Web of Science, Cochrane Library, and ClinicalTrials.gov from 2002 to December 2, 2020. We mainly pooled the adjusted hazard ratios (HRs), mean difference (MD) or risk ratios (RRs) of viral clearance delay and did subgroup analyses by doses and the severity of illness.Results One trial and 38 observational studies, with a total of 7119 patients, were identified. Glucocorticoids treatment was associated with delayed viral clearance in COVID-19 (Adjusted HR 1.71, 95% CI 1.51 to 1.94, I2=22%, PI 1.45 to 2.01), based on moderate-quality evidence. In subgroup analyses, risk of viral clearance delay was significantly higher among COVID-19 patients being mild or moderate ill (adjusted HR 1.94, 95% CI 1.39 to 2.70, I2=52%; MD 2.59, 95% CI 1.21 to 3.97, I2=24%), but not in those of being severe or critical ill (adjusted HR 1.85, 95% CI 1.05 to 3.26; MD 0.22, 95% CI -1.85 to 2.29, I2=56%); taking high doses (adjusted HR 1.49, 95% CI 1.03 to 2.15; unadjusted RR 1.47, 95% CI 1.12 to 1.94) rather taking low doses (adjusted HR 1.39, 95% CI 0.93 to 2.08; unadjusted RR 1.33, 95% CI 1.00 to 1.77) or pulse (unadjusted RR 1.85, 95% CI 0.66 to 5.19).Conclusions Glucocorticoids treatment delayed viral clearance in COVID-19 patients of being mild or moderate ill or taking a high dose, rather in those of being severe or critical ill or taking low dose or pulse.

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

Frontiers in Genetics ◽

10.3389/fgene.2021.698590 ◽

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.

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