The Relevance of the OPRM1 118A>G Genetic
Variant for Opioid Requirement in Pain
Treatment: A Meta-Analysis

Background: There is obvious difference in individual response to opioids. Many studies have examined the correlation between the μ-opioid receptor 1 (OPRM1) 118A>G genetic variation and opioid requirement in pain treatment, but the conclusion remains elusive. Objectives: To investigate whether the OPRM1 118A>G genetic variation is associated with the opioid requirement. Study Design: Systematic review and meta-analysis. Methods: PubMed, Cochrane library, and EMBASE databases were systematically searched up to May 5, 2018, using the keywords “OPRM1,” “genetic variant,” “opioid,” and “pain” to identify reviews or meta-analyses on this topic. Two independent reviewers performed the data extraction and assessed study quality. The authors investigated the standardized mean difference (SMD) of opioid requirement between AA homozygotes and G allele carriers. The authors also examined the association between the OPRM1 118A>G genetic variation and adverse effects such as nausea and vomiting. Potential bias was assessed using the Egger’s test and the Begg’s test. Results: A total of 530 articles were retrieved from the databases searched, and 36 studies involving 8,609 patients were included in the final analysis. G allele carriers required a higher mean opioid dose (SMD: 0.17; 95% confidence interval [CI]: [0.12, 0.22]; P < 0.001) and displayed less nausea risk difference (RD): –0.04; 95% CI: [–0.06, –0.01]), but the incident rate of vomiting has no relationship with the genetic variant than AA homozygotes in a random-effects meta-analysis. Although there was no evidence of publication bias (Begg’s test: P = 0.333; Egger’s: P = 0.561), heterogeneity was present among studies (I2 = 54.3%). In the subgroup meta-analyses, there was also significance observed in the postoperative pain setting. Limitations: In all of the articles reviewed, postoperative pain and cancer pain were mostly discussed except for one in other pain setting. Conclusions: In this meta-analysis, the results indicate the OPRM1 A118G polymorphism was associated with the opioid requirement and the adverse effects in pain treatment especially in postoperative pain. This may provide valuable information for clinicians to adopt personalized pain management by properly using the opioids in individual patients. Key words: OPRM1, genetic variation, opioid, pain, side effect, review, meta-analysis

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Gallbladder Retrieval From Epigastric Versus Umbilical Port in Laparoscopic Cholecystectomy: A PRISMA-Compliant Meta-Analysis

Surgical Innovation ◽

10.1177/1553350619890719 ◽

2019 ◽

Vol 27 (2) ◽

pp. 150-159

Author(s):

Francesco Mongelli ◽

Davide La Regina ◽

Irin Zschokke ◽

Marcello Ceppi ◽

Antonjacopo Ferrario di Tor Vajana ◽

...

Keyword(s):

Postoperative Pain ◽

Literature Search ◽

Operative Time ◽

Meta Analysis ◽

Cochrane Library ◽

Trocar Site ◽

First Choice ◽

Significant Difference ◽

Meta Analyses ◽

Adequate Data

Purpose. To date, no evidence supports the retrieval of the gallbladder through a specific trocar site, and this choice is left to surgeons’ preference. The aim of this meta-analysis was to investigate the influence of the trocar site used to extract the gallbladder on postoperative outcomes. Methods. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search of PubMed, Google Scholar, Cochrane Library, and EMBASE databases was performed. Terms used were: (“gallbladder” OR “cholecystectomy”) AND “umbilical” AND (“epigastric” OR “subxiphoid”). Randomized trials comparing the gallbladder retrieval from different trocar sites were considered for further analysis. Results. Literature search revealed 145 articles, of which 7 matched inclusion criteria and reported adequate data about postoperative pain, operative time, port-site infections, and hernias. A total of 876 patients were included, and the gallbladder was extracted through epigastric or umbilical trocar site in 441 and in 435 patients, respectively. A statistically significant difference among groups was noted in terms of postoperative pain at 1, 6, 12, and 24 hours in favor of the umbilical trocar site ( P < .001). No significant differences were noted in postoperative hernia and infection rate, nor in terms of operative time. Conclusions. This meta-analysis shows a statistically significant reduction in terms of postoperative pain at 1, 6, 12, and 24 hours after surgery when the gallbladder is extracted through the umbilical port. Retrieval time, infections, and hernias rate implicate no contraindication for the choice of a specific trocar site to extract specimens. Despite limitations of this study, the umbilical trocar should be favored as the first choice to retrieve the gallbladder.

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Laser Influence on Dental Sensitivity Compared to Other Light Sources Used During In-office Dental Bleaching: Systematic Review and Meta-analysis

Operative Dentistry ◽

10.2341/19-064-l ◽

2020 ◽

Vol 45 (6) ◽

pp. 589-597

Author(s):

BGS Casado ◽

EP Pellizzer ◽

JR Souto Maior ◽

CAA Lemos ◽

BCE Vasconcelos ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Color Change ◽

Meta Analysis ◽

Present Review ◽

Cochrane Library ◽

Light Sources ◽

Eligibility Criteria ◽

Tooth Color ◽

Significant Difference ◽

Meta Analyses

Clinical Relevance The use of laser light during bleaching will not reduce the incidence or severity of sensitivity and will not increase the degree of color change compared with nonlaser light sources. SUMMARY Objective: To evaluate whether the use of laser during in-office bleaching promotes a reduction in dental sensitivity after bleaching compared with other light sources. Methods: The present review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and is registered with PROSPERO (CDR42018096591). Searches were conducted in the PubMed/Medline, Web of Science, and Cochrane Library databases for relevant articles published up to August 2018. Only randomized clinical trials among adults that compared the use of laser during in-office whitening and other light sources were considered eligible. Results: After analysis of the texts retrieved during the database search, six articles met the eligibility criteria and were selected for the present review. For the outcome dental sensitivity, no significant difference was found favoring any type of light either for intensity (mean difference [MD]: −1.60; confidence interval [CI]: −3.42 to 0.22; p=0.09) or incidence (MD: 1.00; CI: 0.755 to 1.33; p=1.00). Regarding change in tooth color, no significant differences were found between the use of the laser and other light sources (MD: −2.22; CI: −6.36 to 1.93; p=0.29). Conclusions: Within the limitations of the present study, laser exerts no influence on tooth sensitivity compared with other light sources when used during in-office bleaching. The included studies demonstrated that laser use during in-office bleaching may have no influence on tooth color change.

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A systematic review of pharmacist-led audit and feedback interventions to influence prescribing behaviour in general practice settings

International Journal of Pharmacy Practice ◽

10.1093/ijpp/riab015.041 ◽

2021 ◽

Vol 29 (Supplement_1) ◽

pp. i34-i35

Author(s):

M Carter ◽

N Abutheraa ◽

N Ivers ◽

J Grimshaw ◽

S Chapman ◽

...

Keyword(s):

General Practice ◽

Systematic Reviews ◽

Health Professionals ◽

Meta Analysis ◽

Cochrane Review ◽

Audit And Feedback ◽

Cochrane Library ◽

Randomised Trials ◽

Prescribing Behaviour ◽

Meta Analyses

Abstract Introduction Audit and Feedback (A&F) involves measuring data about practice, comparing it with clinical guidelines, professional standards or peer performance, and then feeding back the data to individuals/groups of health professionals to encourage change in practice (if required). A 2012 Cochrane review (1) found A&F was effective in changing health professionals’ behaviour and suggested that the person who delivers the A&F intervention influences its effect. Increasingly, pharmacists work in general practice and often have responsibility for medication review and repeat prescriptions. The effectiveness of pharmacist-led A&F in influencing prescribing behaviour is uncertain. Aim This secondary analysis from an ongoing update of the original Cochrane review aims to identify and describe pharmacist-led A&F interventions and evaluate their impact on prescribing behaviour in general practice compared with no intervention. Methods This sub-review is registered with PROSPERO: CRD42020194355 and complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (2). For the updated Cochrane review, the Cochrane Effective Practice and Organization of Care Group searched MEDLINE (1946 to present), EMBASE, CINAHL and Cochrane Library (March 2019) to identify randomised trials featuring A&F interventions. For this sub-review, authors screened titles and abstracts (May 2020) to identify trials involving pharmacist-led A&F interventions in primary care, extracted data, and assessed risk of bias (RoB) in eligible studies. Review results are summarised descriptively. Heterogeneity will be assessed and a random-effects meta-analysis is planned. Publication bias for selected outcomes and the certainty of the body of evidence will be evaluated and presented. Sub-group analyses will be conducted. Results Titles and abstracts of 295 studies identified for inclusion in the Cochrane A&F review update were screened. Eleven studies (all cluster-randomised trials) conducted in 9 countries (Denmark, Italy, Netherlands, Norway, Republic of Ireland, UK, Australia, Malaysia, USA) were identified for inclusion (Figure 1). Six studies had low RoB, two had high risk due to dissimilarities between trial arms at baseline and/or insufficient detail about randomisation, and three studies had unclear RoB. Studies examined the effect of A&F on prescribing for specific conditions (e.g. hypertension), medications (e.g. antibiotics), populations (e.g. patients >70), and prescribing errors (e.g. inappropriate dose). The pharmacist delivering A&F was a colleague of intervention participants in five studies. Pharmacists’ levels of skill and experience varied; seven studies reported details of pharmacist training undertaken for trial purposes. A&F interventions in nine studies demonstrated changes in prescribing, including reductions in errors or inappropriate prescribing according to the study aims and smaller increases in unwanted prescribing compared with the control group. Data analyses are ongoing (results will be available for the conference). Conclusion The preliminary results demonstrate the effectiveness of pharmacist-led A&F interventions in different countries and health systems with influencing prescribing practice to align more closely with guidance. Studies measured different prescribing behaviours; meta-analysis is unlikely to include all 11 studies. Further detailed analysis including feedback format/content/frequency and pharmacist skill level/experience, work-base (external/internal to recipients), will examine the impact of specific features on intervention effectiveness. References 1. Ivers N, Jamtvedt G, Flottorp S, Young JM, Odgaard-Jensen J, French SD, et al. Audit and feedback: effects on professional practice and healthcare outcomes. Cochrane Database Syst Rev. 2012(6):CD000259. 2. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

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Resting Heart Rate as a Predictor of Cancer Mortality: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10071354 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1354

Author(s):

Diana P. Pozuelo-Carrascosa ◽

Iván Cavero-Redondo ◽

I.M. Lee ◽

Celia Álvarez-Bueno ◽

Sara Reina-Gutierrez ◽

...

Keyword(s):

Heart Rate ◽

Cancer Mortality ◽

Meta Analysis ◽

Positive Association ◽

Cochrane Library ◽

Resting Heart Rate ◽

Potential Marker ◽

Meta Analyses ◽

Risk Of Cancer ◽

The Relationship

This work was aimed to synthetize the evidence available about the relationship between resting heart rate (RHR) and the risk of cancer mortality. A computerized search in the Medline, EMBASE, Web of Science, and Cochrane Library databases from their inception to 24 September 2020 was performed. We performed three meta-analyses: (1) cancer mortality comparing the “less than 60 bpm” and “more than 60 bpm” categories; (2) cancer mortality comparing “less than 60 bpm”, “60 to 80 bpm”, and “more than 80 bpm” categories; and (3) analysis for 10–12 and 20 bpm increase in RHR and risk of cancer mortality. Twenty-two studies were included in the qualitative review, and twelve of them met the inclusion criteria for the meta-analysis. Our results showed a positive association between RHR and the risk of cancer mortality. This association was shown in a meta-analysis comparing studies reporting mean RHR values below and above 60 bpm, when comparing three RHR categories using less than 60 bpm as the reference category and, finally, in dose response analyses estimating the effect of an increase of 10–12 bpm in RHR, both in men and in women. In conclusion, a low RHR is a potential marker of low risk of cancer mortality.

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Comparative efficacy and safety of oral or transdermal opioids in the treatment of knee or hip osteoarthritis: a systematic review and Bayesian network meta-analysis protocol

BMJ Open ◽

10.1136/bmjopen-2018-022142 ◽

2018 ◽

Vol 8 (10) ◽

pp. e022142

Author(s):

Jun Wang ◽

Yin Wang ◽

Hui Zhang ◽

Ming Lu ◽

Weilu Gao ◽

...

Keyword(s):

Bayesian Network ◽

Meta Analysis ◽

Hip Osteoarthritis ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Efficacy And Safety ◽

Meta Analyses ◽

Transdermal Opioids ◽

And Function

IntroductionOsteoarthritis is a common degenerative joint disease that eventually leads to disability and poor quality of life. The main symptoms are joint pain and mobility disorders. If the patient has severe pain or other analgesics are contraindicated, opioids may be a viable treatment option. To evaluate and compare the efficacy and safety of opioids in the treatment of knee or hip osteoarthritis, we will integrate direct and indirect evidence using a Bayesian network meta-analysis to establish hierarchies of these drugs.Methods and analysisWe will search the Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Web of Science and PsycINFO databases as well as published and unpublished research in international registries and regulatory agency websites for osteoarthritis reports published prior to 5 January 2018. There will be no restrictions on the language. Randomised clinical trials that compare oral or transdermal opioids with other various opioids, placebo or no treatment for patients with knee or hip osteoarthritis will be included. The primary outcomes of efficacy will be pain and function. We will use pain and function scales to evaluate the main outcomes. The secondary outcomes of safety will be defined as the proportion of patients who have stopped treatment due to side effects. Pairwise meta-analyses and Bayesian network meta-analyses will be performed for all related outcome measures. We will conduct subgroup analyses and sensitivity analyses to assess the robustness of our findings. The Grading of Recommendations, Assessment, Development and Evaluations framework will be used to assess the quality of the evidence contributing to each network assessment.Ethics and disseminationThis study does not require formal ethical approval because individual patient data will not be included. The findings will be disseminated through peer-reviewed publications or conference presentations.PROSPERO registration numberCRD42018085503.

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Antibiotic prophylaxis for prevention against Lyme disease following tick bite: an updated systematic review and meta-analysis

BMC Infectious Diseases ◽

10.1186/s12879-021-06837-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Guozhong Zhou ◽

Xin Xu ◽

Yu Zhang ◽

Peng Yue ◽

Shiqi Luo ◽

...

Keyword(s):

Lyme Disease ◽

Antibiotic Prophylaxis ◽

Meta Analysis ◽

Treatment Strategies ◽

Tick Bite ◽

Cochrane Library ◽

Control Group ◽

Sufficient Power ◽

Detailed Assessment ◽

Meta Analyses

Abstract Background In areas where Lyme disease is endemic, bites from ticks are common, but no vaccine is currently available against Lyme disease for humans. Therefore, the feasibility of using antibiotic prophylaxis to prevent Lyme disease after a tick bite is worth further exploration. Previous meta-analyses lack sufficient power to demonstrate the efficacy of about antibiotic prophylaxis for the prevention of Lyme disease following a tick bite. In this study, we explored more precise evidence and attempted to identify and update optimum treatment strategies. Methods We searched PubMed, Embase, and the Cochrane Library for studies until March 23, 2021. We included studies if the enrolled patients were randomly allocated to a treatment or control group within 72 h following a tick bite and had no clinical evidence of Lyme disease at enrolment. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for data abstraction. Two authors (GZZ and XX) independently reviewed the abstracts and identified articles for detailed assessment. We used a random-effects model to calculate the pooled results and reported the 95% confidence interval (CI). Study quality was assessed using a modified Jadad scale, and publication bias was assessed using Egger’s test. We calculated the risk ratio (RR) for the rates of unfavorable events in patients who received intervention versus the control group. This study is registered with PROSPERO, number CRD42021245002. Results Six studies (3,766 individuals) were included. The pooled rate of unfavorable events in persons receiving treatment and the control group were 0.4% (95%CI: 0.1–1.1%) and 2.2% (95%CI: 1.6–3.0%), respectively. The pooled RR was 0.38 (95%CI: 0.22–0.66). Subgroup analysis revealed that the pooled RR was 0.29 (95%CI: 0.14–0.60) in the single-use 200-mg doxycycline group; 0.28 (95%CI: 0.05–1.67) in a 10-day course group (Amoxicillin, Penicillin or tetracycline); and 0.73 (95%CI: 0.25–2.08) in a topical antibiotic treatment group (Azithromycin). Conclusions The available evidence supports the use of antibiotics for the prevention of Lyme disease, and reveals advantages of using single-dose; however, further confirmation is needed.

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The Optimal Time of Applying Enteral Immunonutrition in Esophageal Cancer Patients Receiving Esophagectomy: A Network Meta-Analysis of Randomized Clinical Trials

10.21203/rs.3.rs-235527/v1 ◽

2021 ◽

Author(s):

Xu Tian ◽

Yan-Fei Jin ◽

Zhao-Li Zhang ◽

Hui Chen ◽

Wei-Qing Chen ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Patients ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Infectious Complications ◽

Cochrane Library ◽

Optimal Time ◽

Registration Number ◽

Meta Analyses ◽

The Impact

Abstract Background: Enteral immunonutrition (EIN) has been extensively applied in cancer patients, however its role in esophageal cancer (EC) patients receiving esophagectomy remains unclear. We performed this network meta-analysis to investigate the impact of EIN on patients undergoing surgery for EC and further determine the optimal time of applying EIN.Methods: We searched PubMed, EMBASE, Cochrane library, and China National Knowledgement Infrastructure (CNKI) to identify eligible studies. Categorical data was expressed as the odds ratio with 95% confidence interval (CI), and continuous data was expressed as mean difference (MD) with 95% CI. Pair-wise and network meta-analysis was performed to evaluate the impact of EIN on clinical outcomes using RevMan 5.3 and ADDIS V.1.16.8 softwares. The surface under the cumulative ranking curve (SUCRA) was calculated to rank all nutritional regimes.Results: Total 14 studies involving 1071 patients were included. Pair-wise meta-analysis indicated no difference between EIN regardless of the application time and standard EN (SEN), however subgroup analyses found that postoperative EIN was associated with decreased incidence of total infectious complications (OR=0.47; 95%CI=0.26 to 0.84; p=0.01) and pneumonia (OR=0.47; 95%CI=0.25 to 0.90; p=0.02) and shortened LOH (MD=-1.01; 95%CI=-1.44 to -0.57; p<0.001) compared to SEN, which were all supported by network meta-analyses. Ranking probability analysis further indicated that postoperative EIN has the highest probability of being the optimal option in terms of these three outcomes.Conclusions: Postoperative EIN should be preferentially utilized in EC patients undergoing esophagectomy because it has optimal potential of decreasing the risk of total infectious complications and pneumonia and shortening LOH.OSF registration number: 10.17605/OSF.IO/KJ9UY.

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Movement-Evoked Pain Versus Pain at Rest in Postsurgical Clinical Trials and Meta-Analyses: Protocol for a Follow-Up Systematic Review

JMIR Research Protocols ◽

10.2196/15309 ◽

2020 ◽

Vol 9 (1) ◽

pp. e15309

Author(s):

Daenis Camiré ◽

Jason Erb ◽

Henrik Kehlet ◽

Timothy Brennan ◽

Ian Gilron

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Postoperative Pain ◽

Primary Outcome ◽

Outcome Measure ◽

Pain Treatment ◽

Pain Outcome ◽

Meta Analyses ◽

Pain At Rest

Background Postoperative pain is one of the most prevalent and disabling complications of surgery that is associated with personal suffering, delayed functional recovery, prolonged hospital stay, perioperative complications, and chronic postsurgical pain. Accumulating evidence has pointed to the important distinction between pain at rest (PAR) and movement-evoked pain (MEP) after surgery. In most studies including both measures, MEP has been shown to be substantially more severe than PAR. Furthermore, as MEP is commonly experienced during normal activities (eg, breathing, coughing, and walking), it has a greater adverse functional impact than PAR. In a previous systematic review conducted in 2011, only 39% of reviewed trials included MEP as a trial outcome and 52% failed to identify the pain outcome as either PAR or MEP. Given the recent observations of postsurgical pain trials that continue to neglect the distinction between PAR and MEP, this updated review seeks to evaluate the degree of progress in this area. Objective This updated review will include postsurgical clinical trials and meta-analyses in which the primary outcome was early postoperative pain intensity. The primary outcome for this review is the reporting of MEP (vs PAR) as an outcome measure for each trial and meta-analysis. Secondary outcomes include whether trials and meta-analyses distinguished between PAR and MEP. Methods To be consistent with the 2011 review that we are updating, this review will again focus on randomized controlled trials and meta-analyses, from Medical Literature Analysis and Retrieval System Online and EMBASE databases, focusing on pain treatment after thoracotomy, knee arthroplasty, and hysterectomy in humans. Trials and meta-analyses will be characterized as to whether or not they assessed PAR and MEP; whether their pain outcome acknowledged the distinction between PAR and MEP; and, for trials assessing MEP, which pain-evoking maneuver(s) were used. Results Scoping review and pilot data extraction are under way, and the results are expected by March 2020. Conclusions It is our belief that every postsurgical analgesic trial should include MEP as an outcome measure. The previous 2011 review was expected to have an impact on more widespread assessment of MEP in subsequent postoperative pain treatment trials. Thus, the purpose of this follow-up review is to reevaluate the frequency of use of MEP as a trial outcome, compared with PAR, in more recently published postoperative pain trials. Trial Registration PROSPERO CRD42019125855; https://tinyurl.com/qw9dty8 International Registered Report Identifier (IRRID) DERR1-10.2196/15309

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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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Association of genetic variants in enamel-formation genes with dental caries: A meta- and gene-cluster analysis

10.1101/2020.09.19.20198044 ◽

2020 ◽

Author(s):

Xueyan Li ◽

DI LIU ◽

Sun Yang ◽

Jingyun Yang ◽

Youcheng Yu

Keyword(s):

Cluster Analysis ◽

Dental Caries ◽

Gene Cluster ◽

Genetic Variants ◽

Literature Search ◽

Genetic Variant ◽

Meta Analysis ◽

Cochrane Library ◽

Systematic Literature Search ◽

Enamel Formation

Previous studies have reported the association between multiple genetic variants in enamel formation-related genes and the risk of dental caries with inconsistent results. We performed a systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases for studies published before March 21, 2020 and conducted meta-, gene-based and gene-cluster analysis on the association between genetic variants in enamel- formation-related genes and the risk of dental caries. Our systematic literature search identified 21 relevant publications including a total of 24 studies for analysis. The genetic variant rs17878486 in AMELX was significantly associated with dental caries risk (OR=1.40, 95% CI: 1.02-1.93, P=0.037). We found no significant association between the risk of dental caries with rs12640848 in ENAM (OR=1.15, 95% CI: 0.88-1.52, P=0.310), rs1784418 in MMP20 (OR=1.07, 95% CI: 0.76-1.49, P=0.702) and rs3796704 in ENAM (OR=1.06, 95% CI: 0.96-1.17, P=0.228). Gene-based analysis indicated that multiple genetic variants in AMELX showed joint association with the risk of dental caries (6 variants; P<10-5), so did genetic variants in MMP13 (3 variants; P=0.004), MMP2 (3 variants; P<10-5), MMP20 (2 variants; P<10-5) and MMP3 (2 variants; P<10-5). The gene-cluster analysis indicated a significant association between the genetic variants in this enamel-formation gene cluster and the risk of dental caries (P<10-5). The present meta-analysis revealed that genetic variant rs17878486 in AMELX were associated with dental caries, and multiple genetic variants in enamel-formation-related genes jointly contribute to the risk of dental caries, supporting the role of genetic variants in the enamel-formation genes in the etiology of dental caries.

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