Venice Criteria Research Articles

Genetic variations in immune mediators and prostate cancer risk: A field synopsis with Bayesian calculations

ObjectiveOur study aimed to revaluate the significant data from meta-analyses on genetic variations in immune mediators and the risk of prostate cancer (PCa) by Bayesian approaches. MethodsWe performed a search on the literature before September 5th, 2023, for meta-analytic studies on polymorphisms in immune mediator genes and the risk of PCa. Two Bayesian approaches were used to assess the level of noteworthiness in the meta-analytic data: the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10−3 and 10−6. The quality evaluation of studies was performed with the Venice criteria. Gene-gene and protein–protein networks were designed for the genes and products enrolled in the results. ResultsAs results, 18 meta-analyses on 17 polymorphisms in several immune mediator genes were included (IL1B rs16944/rs1143627, IL4 rs2243250/rs2227284/rs2070874, IL6 1800795/rs1800796/rs1800797, IL8 rs4073, IL10 rs1800896/rs1800871/rs1800872, IL18 rs1946518, COX2 rs2745557, TNFA rs361525 and PTGS2 rs20417/689470). The Bayesian calculations showed the rs1143627 and the rs1946518 polymorphisms in IL1B and IL18 genes, respectively, were noteworthy. The Venice criteria showed that only four studies received the highest level of evidence. The gene-gene and protein–protein networks reinforced the findings on IL1B and IL18 genes. ConclusionIn conclusion, this current Bayesian revaluation showed that the rs1143627 and the rs1946518 polymorphisms in the IL1B and IL18 genes, respectively, were noteworthy biomarker candidates for PCa risk.

Genetic Variants Associated With Response to Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer Patients: A Field Synopsis and Meta-Analysis.

Background: Publications on the associations of genetic variants with the response to platinum-based chemotherapy (PBC) in NSCLC patients have surged over the years, but the results have been inconsistent. Here, a comprehensive meta-analysis was conducted to combine eligible studies for a more accurate assessment of the pharmacogenetics of PBC in NSCLC patients. Methods: Relevant publications were searched in PubMed, Scopus, and Web of Science databases through 15 May 2021. Inclusion criteria for eligible publications include studies that reported genotype and allele frequencies of NSCLC patients treated with PBC, delineated by their treatment response (sensitive vs. resistant). Publications on cell lines or animal models, duplicate reports, and non-primary research were excluded. Epidemiological credibility of cumulative evidence was assessed using the Newcastle-Ottawa Scale (NOS) and Venice criteria. Begg's and Egger's tests were used to assess publication bias. Cochran's Q-test and I2 test were used to calculate the odds ratio and heterogeneity value to proceed with the random effects or fixed-effects method. Venice criteria were used to assess the strength of evidence, replication methods and protection against bias in the studies. Results: A total of 121 publications comprising 29,478 subjects were included in this study, and meta-analyses were performed on 184 genetic variants. Twelve genetic variants from 10 candidate genes showed significant associations with PBC response in NSCLC patients with strong or moderate cumulative epidemiological evidence (increased risk: ERCC1 rs3212986, ERCC2 rs1799793, ERCC2 rs1052555, and CYP1A1 rs1048943; decreased risk: GSTM1 rs36631, XRCC1 rs1799782 and rs25487, XRCC3 rs861539, XPC rs77907221, ABCC2 rs717620, ABCG2 rs2231142, and CDA rs1048977). Bioinformatics analysis predicted possible damaging or deleterious effects for XRCC1 rs1799782 and possible low or medium functional impact for CYP1A1 rs1048943. Conclusion: Our results provide an up-to-date summary of the association between genetic variants and response to PBC in NSCLC patients.

Discovering the link between IL12RB1 gene polymorphisms and tuberculosis susceptibility: a comprehensive meta-analysis.

Numerous studies suggest that the risk of tuberculosis (TB) is linked to gene polymorphisms of the interleukin-12 receptor b subunit 1 (IL12RB1), but the association between IL12RB1 polymorphisms and TB susceptibility has not been thoroughly investigated. A meta-analysis was conducted based on eight case-control studies with 10,112 individuals to further explore this topic. A systematic search of PubMed, Web of Science, Excerpt Medica Database, and Google Scholar up until April 6th, 2023 was performed. ORs and 95% CIs were pooled using the random-effect model. The epidemiological credibility of all significant associations was assessed using the Venice criteria and false-positive report probability (FPRP) analyses. The IL12RB1 rs11575934 and rs401502 showed solid evidence of no significant association with TB susceptibility. However, a weak association was observed between the IL12RB1 rs375947 biomarker and pulmonary tuberculosis (PTB) susceptibility (OR = 1.64, 95% CI: 1.22, 2.21). These findings should be confirmed through larger, better-designed studies to clarify the relationship between biomarkers in IL12RB1 gene and different types of TB susceptibility.

Mapping the genetic architecture of idiopathic pulmonary fibrosis: Meta-analysis and epidemiological evidence of case-control studies

BackgroundIdiopathic pulmonary fibrosis (IPF) is a rare and devastating fibrotic lung disorder with unknown etiology. Although it is believed that genetic component is an important risk factor for IPF, a comprehensive understanding of its genetic landscape is lacking. Hence, we aimed to highlight the susceptibility genes and pathways implicated in IPF pathogenesis through a two-staged systematic literature search of genetic association studies on IPF, followed by meta-analysis and pathway enrichment analysis. MethodsThis study was performed based on PRISMA guidelines (PROSPERO, registration number: CRD42022297970). The first search was performed (using PubMed and Web of Science) retrieving a total of 5642 articles, of which 52 were eligible for inclusion in the first stage. The second search was performed (using PubMed, Web of Science and Scopus) for ten polymorphisms, identified from the first search, with 2 or more studies. Finally, seven polymorphisms, [rs35705950/MUC5B, rs2736100/TERT, rs2609255/FAM13A, rs2076295/DSP, rs12610495/DPP9, rs111521887/TOLLIP and rs1800470/TGF-β1] qualified for meta-analyses. The epidemiological credibility was evaluated using Venice criteria. ResultsFrom the systematic review, 222 polymorphisms in 118 genes showed a significant association with IPF susceptibility. Meta-analyses findings revealed significant association of rs35705950/T [OR = 3.92(3.26–4.57)], rs2609255/G [OR = 1.50(1.18–1.82)], rs2076295/G [OR = 1.19(0.82–1.756)], rs12610495/G [OR = 1.28(1.12–1.44)], rs2736100/C [OR = 0.68(0.54–0.82), rs111521887/G [OR = 1.34(1.06–1.61)] and suggestive evidence for rs1800470/T [OR = 1.08(0.82–1.34)] with IPF susceptibility. Four polymorphisms- rs35705950/MUC5B, rs2736100/TERT, rs2076295/DSP and rs111521887/TOLLIP, exhibited substantial epidemiological evidence supporting their association with IPF risk. Gene ontology and pathway enrichment analysis performed on IPF risk-associated genes identified a critical role of genes in mucin production, immune response and inflammation, host defence, cell–cell adhesion and telomere maintenance. ConclusionsOur findings present the most prominent IPF-associated genetic risk variants involved in alveolar epithelial injuries (MUC5B, TERT, FAM13A, DSP, DPP9) and epithelial-mesenchymal transition (TOLLIP, TGF-β1), providing genetic and biological insights into IPF pathogenesis. However, further experimental research and human studies with larger sample sizes, diverse ethnic representation, and rigorous design are warranted.

Association between the oxidative stress gene polymorphism and chronic obstructive pulmonary disease risk: a meta-analysis

BackgroundThe association between the oxidative stress gene polymorphism and chronic obstructive pulmonary disease (COPD) risk has been extensively studied but the results have been controversial. This study aimed to investigate the overall association between the oxidative stress gene including glutathione S-transferase (GST), epoxide hydrolase exon (EPHX), superoxide dismutase (SOD), catalase (CAT), cytochrome P450 system (CYP) and heme oxygenase (HO-1) polymorphism and the risk of COPD.MethodsWe searched the PubMed and EMBASE database to identify studies that investigated the association between the oxidative stress gene polymorphism and risk of COPD. The relevant data were extracted and statistical analyses were performed using the Revman 5.4 and STATA 12 software. Dominant genetic model, recessive model, co-dominant model, heterozygote model, and allele model were analyzed. Venice criteria and publication bias were conducted to access the credibility and reliability.ResultsIn total, 63 publications including 14,733 patients and 50,570 controls were included in the meta-analysis.15 genetic variants of 6 genes were analyzed, and 7 SNPs in GSTP1, CAT, CYP, SOD were first analyses until now. In our study, EPHX T113C C allele, GSTM1 null, GSTT1 null, GSTP1 A313G G and C341T T allele, CYP1A1 MspI C allele, SOD3 A213G G allele and L type in Ho-1 showed increased COPD risk, especially in Asians. T allele in CAT C262T and C allele in SOD2 Val 9 Ala were associated with decreased COPD risk. To avoid high heterogeneity and publications bias, subgroups analysis was performed in accord with HWE and ethnicity. Publication bias was assessed by Begg’s funnel plots and Egger’s test, and no publication bias were found for recessive models. 4 variants were identified with strong levels of epidemiological evidence of associations with the COPD risk.ConclusionsOur results confirm that oxidative stress gene polymorphism was associated with COPD risk. These finding can improve human understanding of this disease gene molecular level and enable early intervention and prevention of COPD. Well-designed studies with large sample sizes are essential to clarify the association of these significant variants with the susceptibility to COPD.

Relationship between esophageal squamous cell carcinoma risk and alcohol-related ALDH2 and ADH1B polymorphisms: Evidence from a meta-analysis and Mendelian randomization analysis.

Previous studies have shown that ALDH2 and ADH1B genes may be associated with alcohol metabolism and the risk of esophageal squamous cell carcinoma (ESCC), with inconsistent results. This meta-analysis aimed at comprehensively assessing the associations between ALDH2 and ADH1B polymorphisms and the risk of ESCC to synthesize and clarify the evidence. We calculated summary estimates of the associations between four genetic variants (rs671 and rs674 in ALDH2, and rs1229984 and rs1042026 in ADH1B) and the ESCC risk across 23 publications in the additive model and allelic model. Venice criteria, Bayesian false discovery probability (BFDP), and false-positive reporting probability (FPRP) were used to assess the strength of epidemiological evidence. Heterogeneity among studies was evaluated by using the Higgin's I2 statistic, and publication bias was assessed by using funnel plots and Begg's test. A Mendelian randomization (MR) analysis was performed to determine the causal association between alcohol intake and esophageal cancer risk. Data from the HaploReg v4.1 and PolyPhen-2 were analyzed for functional annotations. Of the four genetic variants, rs671 of ALDH2 was associated with a significantly reduced risk of ESCC (OR: 0.60, 95% CI: 0.50-0.73), whereas rs1229984 of ADH1B was associated with a significantly increased risk (2.50, 95% CI: 1.70-3.69) in the additive model. In the allelic model, the variant rs1229984 of ADH1B also increased the risk of ESCC (OR: 1.50; 95% CI: 1.21-1.87). The result for the variant rs671 was considered as strong epidemiological evidence. Functional annotations identified that the four variants were related to the enhancer histone marks and motif changes. The other two variants were not associated with the ESCC risk (rs674 of ALDH2 OR: 1.22, 95% CI: 0.71-2.12; rs1042026 of ADH1B OR: 1.28, 95% CI: 0.52-3.14) in the additive model. The MR analysis did not find a causal effect of alcohol on the esophageal cancer risk. The results showed that ADH1B rs1229984 was significantly associated with an increased the risk of ESCC.

Genetic association of beta-lactams-induced hypersensitivity reactions: A systematic review of genome-wide evidence and meta-analysis of candidate genes

ImportanceBeta-lactams (BLs) are the most prescribed antibiotics, being the most frequent cause of drug allergy. However, the association between BL allergy and genetic variations is still unclear. ObjectiveThis systematic review and meta-analysis aimed to summarize the genetic effects of BL-induced hypersensitivity using existing evidence. MethodsWe searched PubMed, Medline, Scopus, EMBASE, CINAHL, and Cochrane Library from inception to September 15, 2022 with no language restriction. Genetic association studies investigating genetic variant/polymorphism and risk of drug-induced hypersensitivity reactions among individuals receiving BL-antibiotics were included. We excluded studies of acute interstitial nephritis, drug-induced liver injury, serum sickness, and isolated drug fever. Data were comprehensively synthesized and quality of study were assessed using STrengthening the Reporting of Genetic Association Studies (STREGA). The record screening, extraction and quality assessment were performed by two reviewers and discussions were made to resolve discrepancies. The effects of each variant were pooled and evaluated by modified Venice criteria. ResultsA total of 9276 records were identified, and 31 studies were eligible for inclusion. Twenty-seven were candidate-gene association studies (5416 cases and 5939 controls), while the others were next-generation sequencing (NGS) or genome-wide association studies (GWASs) (119 838 cases and 1 487 111 controls). Forty-nine polymorphisms were identified and most of them located in allergic reaction pathways. Meta-analyses of 15 candidate variants in a mixture of both immediate and non-immediate reactions revealed weak genetic effects of rs1801275 (8 studies; n = 1,560; odd ratio 0.73; 95%CI: 0.57–0.93) and rs20541 (4 studies; n = 1,482; odd ratio 1.34; 95%CI: 1.07–1.68) in IL4R and IL13, respectively. Results from GWASs and NGS identified, and confirmed associations in HLA regions including HLA-DRA, HLA-B, HLA-DQA, HLA-DRB1, and HLA-DRB3. ConclusionOur study summarized genetic evidence influencing BL-induced hypersensitivity and estimated effects of potential variants. We postulated that the genomic studies provide better insights to the mechanism of reactions and suggest potential effects of HLA Class II variants. However, results were inconsistent and unable to generalize in different settings. Further high-throughput studies with a well-defined function, epigenetic interaction, incorporated with clinical factors, would be beneficial for risk identification in BL-induced hypersensitivity.

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility: an updated meta-analysis.

Widely regarded as one of the most prevalent malignancies worldwide, gastric cancer (GC) is a common clinical condition of the digestive system. Reviewing 14 meta-analyses that evaluated the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and GC risk, we observed inconsistent results, and the credibility of the significant correlation between the statistical results was ignored. With the aim of further exploring the association between MTHFR C677T and A1298C and the risk of GC, we searched electronic databases, pooling 43 relevant studies and calculating odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for each of the five genetic models. Subgroup and regression analyses were performed to look for sources of heterogeneity and publication bias was assessed by funnel plots. To assess the plausibility of statistically significant associations, we used the FPRP test and the Venice criteria. Overall data analysis showed that MTHFR C677T polymorphism was significantly associated with GC risk, especially in Asians, while MTHFR A1298C polymorphism was not associated with GC risk. However, in subgroup analysis by hospital-based controls, we found that MTHFR A1298C might be a protective factor for GC. After credibility assessment, the statistical association between MTHFR C677T and GC susceptibility study was classified as 'less credible positive result', while the result of MTHFR A1298C was considered unreliable. In summary, the present study strongly suggests that MTHFR C677T and A1298C polymorphisms are not significantly associated with the GC risk.

Gene variations related to the hepatocellular carcinoma: Results from a field synopsis and Bayesian revaluation

Hepatocellular carcinoma (HCC) is considered as the second cause of cancer-related deaths worldwide. Genetic variations are associated with HCC risk, an issue that has been the subject of several meta-analyses. However, meta-analyses have an important limitation on the likelihood of false positive data. Henceforth, this study aimed to assess the level of noteworthiness in the meta-analyses by means of a Bayesian approach. A systematic search was performed for meta-analyses with associations between gene polymorphisms and HCC. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10−3 and 10−5. The quality of studies was evaluated by the Venice criteria. As additional analyses, the gene-gene and protein–protein networks were designed for these genes and products. As results, we found 33 meta-analytic studies on 45 polymorphisms occurring in 35 genes. A total of 1,280 values for FPRP and BFDP were obtained. Seventy-five for FPRP (5.86%) and 95 for BFDP (14.79%) were noteworthy. In conclusion, the polymorphisms in CCND1, CTLA4, EGF, IL6, IL12A, KIF1B, MDM2, MICA, miR-499, MTHFR, PNPLA3, STAT4, TM6SF2, and XPD genes were considered as noteworthy biomarkers for HCC risk.

Strong Cumulative Evidence of Associations of 6 Single Nucleotide Polymorphisms with Ovarian Cancer Risk: An Umbrella Review

Background: An increasing number of studies have reported associations between single nucleotide polymorphisms (SNPs) and ovarian cancer (OC) risk. However, some of the findings were inconsistent. The objective of this umbrella review was to evaluate the associations comprehensively and quantitatively. Methods: The protocol of this review was registered in PROSPERO (No. CRD42022332222). We searched the PubMed, Web of Science, and Embase databases to identify related systematic reviews and meta-analyses from inception to 15 October 2021. In addition to estimating the summary effect size by using fixed and random effects models and calculating the 95% prediction interval, we evaluated the cumulative evidence for associations with nominally statistical significance based on the Venice criteria and false positive report probability (FPRP). Results: Forty articles were included in this umbrella review, which referred to a total of 54 SNPs. The median number of original studies per meta-analysis was four, while the median number of total subjects was 3455. All included articles had greater than moderate methodological quality. A total of 18 SNPs were nominally statistically associated with OC risk; 6 SNPs (8 genetic models), 5 SNPs (7 genetic models), and 16 SNPs (25 genetic models) were identified as strong, moderate, and weak cumulative evidence, respectively. Conclusion: This umbrella review revealed associations between SNPs and OC risk and suggested strong cumulative evidence of associations of six SNPs (eight genetic models) with OC risk.

Association between the TP53 Arg72Pro Polymorphisms and Gastric Cancer Risk: An Updated Meta-Analysis and Re-Analysis of Systematic Meta-Analyses

Background: A latest Meta-analysis on TP53 Arg72Pro polymorphism with gastric cancer (GC) risk was published in 2015 including 20 literatures, while our study included 43 studies. Moreover, the results of previously published original studies were inconsistent and the credibility of the significant correlation between the statistical results has been ignored. Therefore, an updated Meta-analysis was conducted to further explore these associations. Objective: To explore whether these two gene polymorphisms are related to the risk, clinical manifestations, and pathological features of GC. Methods: We searched several Chinese and English databases. The crude odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the correlation. In addition, false positive reporting probability (FPRP), bayesian false discovery probability (BFDP), and Venice criteria were used to assess the reliability of statistically significant correlation. Results: Overall, the TP53 Arg72Pro polymorphism was related to a significantly increased GC risk (AP vs. AA: OR = 1.12, 95% CI = 1.02 - 1.24; PP + AP vs. AA: OR = 1.12, 95% CI = 1.02 - 1.24; P vs. A: OR = 1.07, 95% CI = 1.00 - 1.15). However, after excluding the low quality and Hardy–Weinberg Disequilibrium (HWD) studies, significant changes were found on the TP53 Arg72Pro polymorphism with GC risk in Caucasians (PP vs. AA: OR = 1.48, 95% CI = 1.01 - 2.16) and non-gastric cancer control groups (PP vs. AP + AA: OR = 1.33, 95% CI = 1.07 - 1.64)). However, the above significant results were considered unreliable after being adjusted with Bayesian error detection probability (BFDP) and false positive reporting probability (FPRP). These unreliable results were confirmed again, and no new reliable results were found in the further sensitivity analysis (only studies that met the quality assessment criteria). Conclusions: After considering the quality of the study and the reliability of the results, this Meta-analysis showed that TP53 codon 72 polymorphisms had no significant correlation with GC risk. Because of various confounding factors, the result that these polymorphisms increase GC risk is more likely to be a false positive result.

Association between OPG polymorphisms and osteoporosis risk: An updated meta-analysis.

Background: Numerous studies have demonstrated an association between osteoprotegerin (OPG) polymorphisms (A163G (rs3102735), T245G (rs3134069), T950C (rs2073617), G1181C (rs2073618)) and osteoporosis risk. However, their conclusions are inconsistent. In addition, some new studies have been updated, and more importantly, previous meta-analyses have not tested for false-positive results. In order to further explore these associations, we recently conducted a meta-analysis. Objectives: To study the relationship between OPG polymorphisms A163G, T245G, T950C, G1181C and the risk of osteoporosis. Methods: PubMed, Medline, International Statistical Institute (ISI), China National Knowledge Infrastructure (CNKI) and China Wanfang Database were used for research searches. Associations were assessed with five genetic models using odds ratios (ORs) with 95% confidence intervals (CIs). In addition, confidence in statistically significant associations was assessed using false-positive report probability (FPRP), Bayesian probability of False discovery (BFDP), and Venice criteria. Results: On the whole, the OPG A163G polymorphism was not significantly associated with risk of osteoporosis. However, in a subgroup analysis, we found that the OPG A163G polymorphism increased the risk of osteoporosis in Caucasians (AG + GG vs AA: OR = 1.35, 95% CI = 1.06-1.73; AA + GG vs AG: OR = 0.64, 95% CI = 0.49-0.82) and the female (G vs A: OR = 1.30, 95% CI = 1.03-1.64; AG + GG vs AA: OR = 1.42, 95% CI = 1.18-1.71). At the same time, the OPG G1181C polymorphism reduces the risk of osteoporosis (C vs G: OR = 0.84, 95% CI = 0.74-0.95; CC vs GG: OR = 0.75, 95% CI = 0.60-0.93; GC + CC vs GG: OR = 0.80, 95% CI = 0.67-0.95; CC vs GG + GC: OR = 0.84, 95% CI = 0.70-1.00). Moreover, a significantly decreased risk of osteoporosis was also discovered in Asian (C vs G: OR = 0.80, 95% CI = 0.66-0.98; CC vs GG: OR = 0.67, 95% CI = 0.47-0.95; GC + CC vs GG: OR = 0.74, 95% CI = 0.58-0.95) and the female (C vs G: OR = 0.85, 95% CI = 0.75-0.97; CC vs GG: OR = 0.77, 95% CI = 0.61-0.96; GC + CC vs GG: OR = 0.79, 95% CI = 0.66-0.95). Finally, we did not find a close association between OPG T245G and T950C polymorphisms and osteoporosis risk. However, when we retained only studies in the control group that was consistent with Hardy-Weinberg equilibrium (HWE) and high-quality scores, we observed that the OPG A163G polymorphism increased the risk of osteoporosis in the overall analysis (G vs A: OR = 1.40, 95% CI = 1.16-1.68; GG vs AA: OR = 1.96, 95% CI = 1.20-3.21; AG + GG vs AA: OR = 1.45, 95% CI = 1.22-1.72). Finally, after the credibility assessment, we concluded that all statistically significant association results in the meta-analysis in this study and those in the previous study were 'positive results with low confidence'. Conclusion: In conclusion, our study concluded that all meaningful results between OPG A163G and G1181C polymorphisms and osteoporosis risk were false-positive results rather than true associations.

Integrative analyses of genes about venous thromboembolism: An umbrella review of systematic reviews and meta-analyses.

In recent years, many studies have found possible links between gene polymorphisms and venous thromboembolism (VTE). By identifying genetic risk factors before facing environmental risk factors such as surgical interventions and COVID-19 vaccination, we could rapidly respond to the risk of VTE. The aim of this study was to perform an umbrella review of genetic variants related to VTE. Integrative gene analysis of VTE was performed to identify critical genetic variations. This study conducted an umbrella review of systematic reviews and meta-analyses. All included studies were selected from the PubMed/MEDLINE database. To select eligible studies, the following variables were extracted: first author name; effect size of each study genetic variant; year of publication; the number of studies included in each article; ethnicity, sample size, P values, and heterogeneity estimates. To assess cumulative evidence in genetic epidemiology about effects of gene polymorphisms on VTE, Human Genome Epidemiology Network's Venice criteria were used. Methodological quality assessment was conducted with JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. Genes provided in the present study with genetic variants associated with VTE were FVL (G1691A), Prothrombin (G20210A), MTHFR (C677T, A1298C), PAI-1 (4G/5G), factor VII activating protease (1601G > A), and endothelial protein C receptor (g.6936A_G, c.4600A_G). Among them, variants in FVL, Prothrombin, MTHFR, and PAI-1 showed high significance. Particularly, variants in Prothrombin (G20210A), MTHFR (C677T), and PAI-1 (4G/5G) had more than 2 types of model significance. The present study performed a systematic review of genetic variants associated with VTE. Our results could lead to a more comprehensive understanding of VTE etiology. These results could give a strategy of prediagnosis about evaluating individual risks of VTE who might be exposed to environmental risk factors.

Cumulative evidence for associations between genetic variants in interleukin 17 family gene and risk of human diseases.

BackgroundGenetic association studies have elucidated the link of variants in the interleukin 17 (IL-17) family genes with susceptibility to human diseases, yet have obtained controversial outcomes. Therefore, we sought to update comprehensive synopsis of variants in the IL-17 family genes with susceptibility to human diseases.MethodsOur study screened the Pubmed and Web of Science to enroll eligible articles and performed a meta-analysis, then graded the cumulative evidence of significant association using Venice criteria and false-positive report probability test, and finally assessed the function of variants with strong evidence.ResultsSeven variants in IL-17 family genes had significant relationships with susceptibility to 18 human diseases identified by meta-analyses. Strong evidence was assigned to 4 variants (IL-17A rs2275913, IL-17A rs8193037, IL-17F rs1889570, IL-17F rs763780) with susceptibility to 6 human diseases (lung and cervical cancer, spondyloarthritis, asthma, multiple sclerosis, rheumatoid arthritis), moderate to 2 variants with risk of 5 diseases, weak to 5 variants with risk of 10 diseases. Bioinformatics analysis suggested that the variants with strong evidence might fall in putative functional regions. Additionally, positive relationships for 5 variants with risk of 4 diseases (based on two datasets) and 14 variants with risk of 21 diseases (based on one dataset) were considered noteworthy.ConclusionsThis study offers updated and comprehensive clues that variants in the IL-17 family genes are significantly linked with susceptibility to cervical, lung cancer, asthma, multiple sclerosis, rheumatoid arthritis and spondyloarthritis, and elucidates the crucial role of the IL-17 regions in the genetic predisposition to cancer or noncancerous diseases.

Freedom of Political Party in The European Convention on Human Rights: EU Practice and The Case of Turkey

Bu çalışmada, Avrupa İnsan Hakları Sözleşmesi’nde (AİHS) siyasi parti özgürlüğünün AB ülke uygulamaları ve Türkiye örneği bakımından araştırılması amaçlanmıştır. Çalışma kapsamında AİHS hükümleri, Avrupa İnsan Hakları Mahkemesi (AİHM) içtihadı, Venedik Kriterleri, Avrupa Konseyi Parlamenterler Meclisi tarafından getirilen standartlar, bazı AB ülkelerindeki uygulamalar ve Türkiye pratiği incelenmiştir. Bu kapsamda iç hukukta siyasi parti özgürlüğüne ilişkin mevzuat ve içtihadın AİHS hükümlerine ve AİHM içtihadına uygunluk yönünden birtakım sorunlar barındırdığı tespiti yapılmıştır. Çalışmada anayasada ve mevzuatta yer alan hükümlerin AİHS hükümleri ve AİHM içtihadı paralelinde yeniden gözden geçirilerek değiştirilmesi gerektiği belirtilmiştir. Ayrıca siyasi parti kapatma davalarında Anayasa Mahkemesinin mer’i mevzuatı AİHM içtihadı ile uyumlu bir yaklaşımla yorumlayarak karar vermesi gerektiği değerlendirmesi yapılmıştır.

Polymorphisms in immune-mediator genes and the risk of dengue virus infection: Lights from a systematic revaluation by Bayesian approaches

Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10-3 and 10-6 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF, MICB, PLCE1, VDR, CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV.

Genetic Variants Associated with Chronic Obstructive Pulmonary Disease Risk: Cumulative Epidemiological Evidence from Meta-Analyses and Genome-Wide Association Studies.

Background Last two decades, many association studies on genetic variants and chronic obstructive pulmonary disease (COPD) risk have been published. But results from different studies are inconsistent. Therefore, we performed this article to systematically evaluate results from previous meta-analyses and genome-wide association studies (GWASs). Material and Methods. Firstly, we retrieved meta-analyses in PubMed, Embase, and China National Knowledge Infrastructure and GWASs in PubMed and GWAS catalog on or before April 7th, 2022. Then, data were extracted and screened. Finally, two main methods—Venice criteria and false-positive report probability test—were used to evaluate significant associations. Results As a result, eighty-eight meta-analyses and 5 GWASs were deemed eligible for inclusion. Fifty variants in 26 genes obtained from meta-analyses were significantly associated with COPD risk. Cumulative epidemiological evidence of an association was graded as strong for 10 variants in 8 genes (GSTM1, CHRNA, ADAM33, SP-D, TNF-α, VDBP, HMOX1, and HHIP), moderate for 6 variants in 5 genes (PI, GSTM1, ADAM33, TNF-α, and VDBP), and weak for 40 variants in 23 genes. Five variants in 4 genes showed convincing evidence of no association with COPD risk in meta-analyses. Additionally, 29 SNPs identified in GWASs were proved to be noteworthy based on the FPRP test. Conclusion In summary, more than half (52.38%) of genetic variants reported in previous meta-analyses showed no association with COPD risk. However, 13 variants in 9 genes had moderate to strong evidence for an association. This article can serve as a useful reference for further studies.

The association between single nucleotide polymorphisms and ovarian cancer risk: A systematic review and network meta-analysis.

The relationship between single nucleotide polymorphisms (SNPs) and ovarian cancer (OC) risk remains controversial. This systematic review and network meta-analysis was aimed to determine the association between SNPs and OC risk. Several databases (PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang databases, China Science and Technology Journal Database, and China Biology Medicine disc) were searched to summarize the association between SNPs and OC published throughout April 2021. Direct meta-analysis was used to identify SNPs that could predict the incidence of OC. Ranking probability resulting from network meta-analysis and the Thakkinstian's algorithm was used to select the most appropriate gene model. The false positive report probability (FPRP) and Venice criteria were further tested for credible relationships. Subgroup analysis was also carried out to explore whether there are racial differences. A total of 63 genes and 92 SNPs were included in our study after careful consideration. Fok1 rs2228570 is likely a dominant risk factor for the development of OC compared to other selected genes. The dominant gene model of Fok1 rs2228570 (pooled OR=1.158, 95% CI: 1.068-1.256) was determined to be the most suitable model with a FPRP <0.2 and moderate credibility. Fok1 rs2228570 is closely linked to OC risk, and the dominant gene model is likely the most appropriate model for estimating OC susceptibility.

Epidemiological evidence for associations between variants in microRNA and cancer risk.

Numerous papers have reported variants in microRNAs (miRNAs) associated with cancer risk; these results, however, are controversial. We seek to offer an updated, comprehensive synopsis of genetic associations between single nucleotide polymorphisms (SNPs) in miRNAs and cancer risk. We did a systematic field synopsis and meta-analysis to investigate 29 SNPs in 24 miRNAs associated with risk of 18 different kinds of cancer based on data from 247 eligible articles. We graded levels of cumulative epidemiological evidence of significant association using Venice criteria and a false-positive report probability (FPRP) test. We constructed functional annotations for these variants using data from the Encyclopedia of DNA Elements Project. We used FPRP to find additional noteworthy associations between 278 SNPs in 117 miRNAs and risk of 26 cancers based on each SNP with one data source. Sixteen SNPs were statistically associated with risk of 17 cancers. We graded the cumulative epidemiological evidence as strong for statistical associations between 10 SNPs in 8 miRNAs and risk of 11 cancers, moderate for 9 SNPs with 12 cancers and weak for 11 SNPs with 11 cancers. Bioinformatics analysis suggested that the SNPs with strong evidence might fall in putative functional regions. In addition, 38 significant associations were observed in 38 SNPs and risk of 13 cancers. This study offered a comprehensive research on miRNA gene variants and cancer risk and provided referenced information for the genetic predisposition to cancer risk in future research.

Evaluation of Association Studies and an Updated Meta-Analysis of VDR Polymorphisms in Osteoporotic Fracture Risk.

Background: Several studies have examined the association between vitamin D receptor (VDR) polymorphisms and osteoporotic fracture risk; however, the results are not uniform. Furthermore, many new articles have been published, and therefore, an updated meta-analysis was performed to further explore these issues. Objectives: The aim of the study was to investigate the association between VDR, BsmI, ApaI, TaqI, FokI, and Cdx2 polymorphisms and osteoporotic fracture risk. Methods: The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between VDR BsmI, ApaI, TaqI, FokI, and Cdx2 polymorphisms and the risk of osteoporotic fracture. We also used the false-positive reporting probability (FPRP) test and the Venice criteria to evaluate the credibility of the statistically significant associations. Results: Overall, this study found that the VDR ApaI and BsmI polymorphisms significantly increased the risk of osteoporotic fracture in European countries and America, respectively. However, when sensitivity analysis was performed after excluding low-quality and Hardy–Weinberg disequilibrium (HWD) studies, it was found that only individuals with the double-mutated genotype have an increased risk of osteoporotic fracture in European countries. In addition, when the credibility of the positive results was assessed, it was found that the positive results were not credible. Conclusion: This meta-analysis indicates that there may be no significant association among the polymorphisms of VDR BsmI, ApaI, TaqI, FokI, and Cdx2 and the risk of osteoporotic fracture. The increased risk of osteoporotic fracture is most likely due to false-positive results.