Preclinical assessment of a recombinant RBD-Fc fusion protein as SARS-CoV-2 candidate vaccine.

Background: Waning immunity and emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlight the need for further research in vaccine development. Methods: A recombinant fusion protein containing the receptor-binding domain (RBD) fused to the human IgG1 Fc (RBD-Fc) was produced in CHO-K1 cells. RBD-Fc was emulsified with four adjuvants to evaluate its immunogenicity. The RBD-specific humoral and cellular immune responses were assessed by ELISA. The virus neutralizing potency of the vaccine was investigated using four neutralization methods. Safety was studied in mice and rabbits, and Antibody-Dependent Enhancement (ADE) effects were investigated by flow cytometry. Results: RBD-Fc emulsified in Alum induced a high titer of anti-RBD antibodies with remarkable efficacy in neutralizing both pseudotyped and live SARS-CoV-2 Delta variant. The neutralization potency dropped significantly in response to the Omicron variant. RBD-Fc induced both TH2 and particularly TH1 immune responses. Histopathologic examinations demonstrated no substantial pathologic changes in different organs. No changes in serum biochemical and hematologic parameters were observed. ADE effect was not observed following immunization with RBD-Fc. Conclusion: RBD-Fc elicits highly robust neutralizing antibodies and cellular immune responses, with no adverse effects. Therefore, it could be considered a promising and safe subunit vaccine against SARS-CoV-2.

High purity and recovery of native filamentous hemagglutinin (FHA) from Bordetella pertussis using affinity chromatography.

Filamentous hemagglutinin (FHA) is a critical adhesion molecule produced by Bordetella pertussis (BP), the causative agent of highly contagious respiratory infection known as whooping cough. FHA plays a pivotal role in the pathogenesis of whooping cough and is a key component of acellular pertussis vaccines (aPV). However, conventional purification methods for FHA often involve labor-intensive processes and result in low purity and recovery rates. Therefore, this study explores the use of monoclonal and polyclonal antibodies as specific tools to achieve highly pure and efficient FHA purification. To generate FHA-specific antibodies, polyclonal antibodies were produced by immunizing sheep and monoclonal antibodies (MAbs) were generated by immunizing mice with recombinant and native FHA. The MAbs were selected based on affinity, isotypes, and specificity, which were assessed through ELISA and Western blot assays. Two immunoaffinity columns, one monoclonal and one polyclonal, were prepared for FHA antigen purification. The purity and recovery rates of these purifications were determined using ELISA, SDS-PAGE, and immunoblotting. Furthermore, the MAbs were employed to develop an ELISA assay for FHA antigen concentration determination. The study's findings revealed that immunoaffinity column-based purification of FHA resulted in a highly pure antigen with recovery rates of approximately 57% ± 6.5% and 59% ± 7.9% for monoclonal and polyclonal columns, respectively. Additionally, the developed ELISA exhibited appropriate reactivity for determining FHA antigen concentration. This research demonstrates that affinity chromatography is a viable and advantageous method for purifying FHA, offering superior purity and recovery rates compared to traditional techniques. This approach provides a practical alternative for FHA purification in the context of aPV development.

Effect of Statins on Serum Levels of TNF-alpha and Interleukin-6 in Patients with Kidney Disease: A Meta-analysis of Randomized Clinical Trials.

BACKGROUND AND OBJECTIVES: Some clinical trials have indicated the beneficial effects of statins in patients with kidney disease, while others have reported no positive effect of statins in these patients. We conducted this meta-analysis to identify the effects of statins on serum levels of interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α) in patients with kidney disease. DESIGNS AND METHODS: A systematic literature search was performed using PubMed, Scopus, and Web of Science databases to identify all studies published from inception to August, 2022. The major outcome variable was the Weighted Mean Difference (WMD). Eligible studies were stratified based on target population, intervention duration, dosage and type of statins, and solubility of statins. RESULTS: Meta-analysis performed on seven publications (8 studies), including 213 patients with kidney disease and 188 control individuals, indicated that the concentration of IL-6 was marginally decreased in patients with kidney disease following statin therapy disease (WMD = -1.15 pg/mL; 95% CI = -2.33 to 0.04, P = 0.05, 2 =68.5%)). The findings of subgroup analysis based on the dosage of statins showed that neither highintensity nor moderate/low-intensity statin treatment could significantly influence the serum level of IL-6. Lipophilic statins were more effective than hydrophilic statins, and they marginally decreased the levels of IL6 (WMD = -1.21 pg/mL; 95% CI = -2.43 to 0, P = 0.05, I2 = 55.7%)). Meta-analysis of four publications (five studies) with 157 patients with kidney disease and 132 control subjects showed that statins reduced the serum levels of TNF-α in patients with kidney disease when compared with control individuals (WMD= -2.66 pg/mL; 95% CI = -4.26 to -1.06, P < 0.001, I2 = 63%). CONCLUSION: Statins only marginally decreased the concentration of IL-6 in patients with kidney disease, but neither high-intensity nor moderate/low-intensity statin treatment could significantly influence the level of IL6. However, statins reduced serum levels of TNF-α in patients with kidney disease.

Statin Therapy and Lipid Indices in Chronic Kidney Disease: A Systematic Review and Meta-analysis of Randomized Control Trials.

BACKGROUND: Several studies have demonstrated the improvement in serum lipoproteins by statins in patients with Chronic Kidney Diseases (CKDs), including End-Stage Renal Disease (ESRD). However, the results of these studies are inconclusive. AIM: We aimed to systematically investigate the effect of statins on lipid profiles of patients with CKD by performing a meta-analysis of Randomized Controlled Trials (RCTs). METHODS: Major electronic databases (Scopus, MEDLINE/PubMed, and ISI Web of Science) were searched from inception to August, 2023, to find randomized controlled trials (RCTs) evaluating the effect of different statins on serum lipoproteins in CKD patients. Weighted Mean Difference (WMD) with 95% Confidence Intervals (CI) was used to estimate the effect size. Trial Sequential Analysis (TSA) was performed to confirm the robustness of the evidence. RESULTS: A total of 18 publications were identified. It was found that statins reduced serum levels of Low-Density Lipoprotein (LDL)-C (WMD = -27.81 mg/dl, 95% CI = -34.47 to -21.15, P < 0.001) and total cholesterol (WMD = -25.44 mg/dl, 95% CI = -34.71 to -16.18, P < 0.001) in patients with CKD compared to the control group. Nonetheless, the effect of statins on High-Density Lipoprotein (HDL)-C (WMD = 0.57 mg/dl, 95% CI = -0.71 to 1.85, P = 0.38) and Triglyceride (TG) (WMD = -9.08 mg/dl, 95% CI = -22.22 to 2.06, P = 0.11) was not statistically significant. The results of TSA confirmed the robustness of the evidence and were consistent with the pooled effect size. The findings of subgroup analysis and time response analysis were also significant. CONCLUSION: It was found that statin therapy reduced the levels of LDL-C and total cholesterol in patients with CKD.

MTHFR gene polymorphisms and susceptibility to myocardial infarction: Evidence from meta-analysis and trial sequential analysis.

Background: This meta-analysis aimed to provide a comprehensive assessment of the association between Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, specifically C677T and A1298C, and the susceptibility to myocardial infarction (MI). Methods: A systematic literature search was conducted in MEDLINE, Web of Science, and Scopus until April 2023 to identify studies investigating the relationship between MTHFR gene polymorphisms (C677T and A1298C) and the risk of MI. Results: The analysis included 66 studies involving 16,860 cases and 20,403 controls for the C677T polymorphism and 18 studies comprising 3162 cases and 3632 controls for the A1298C polymorphism. Significant associations were observed between the C677T polymorphism and MI risk in various genetic models: dominant (OR = 1.16, 95 % CI = 1.06-1.28, P = 0.008), recessive (OR = 1.20, 95 % CI = 1.12-1.28, P < 0.001), allelic (OR = 1.13, 95 % CI = 1.06-1.21, P < 0.001), TT vs. CC (OR = 1.19, 95 % CI = 1.05-1.36, P < 0.001), and CT vs. CC (OR = 1.11, 95 % CI = 1.02-1.21, P = 0.01). Furthermore, an overall analysis indicated a marginally significant association between the A1298C polymorphism and MI risk in the recessive model (OR = 1.27, 95 % CI = 1.06-1.51, P = 0.008), allelic model (OR = 1.18, 95 % CI = 1.01-1.39, P = 0.03), and CC vs. AA model (OR = 1.22, 95 % CI = 1.01-1.47, P = 0.04). Meta-regression analysis revealed that none of the potential factors contributed to the observed heterogeneity. Conclusions: This meta-analysis revealed an association between MTHFR gene C677T and A1298C polymorphisms and the risk of MI.

Novel mouse monoclonal antibodies against Bordetella pertussis pertactin antigen with versatile applications.

BACKGROUND: Pertussis, or whooping cough, is a highly contagious respiratory disease caused by Bordetella pertussis (BP). Pertactin (PRN) is one of the main immunogenic components of BP and is employed in many commercialized acellular pertussis vaccines (aPVs). Purification of this protein by conventional chromatography methods is challenging and commonly requires multiple laborious processes with low recovery. Using specific monoclonal antibodies (mAbs) for the purification of PRN antigen is expected to yield high purity and recovery of the target molecule. METHODS: Recombinant PRN antigen was used to produce mouse mAbs using hybridoma technology. Structural and functional characteristics of the mAbs were assessed by ELISA, immunoblotting, and flow cytometry. Selected mAbs were employed to purify PRN by affinity chromatography, and the purity and recovery of the purified protein were analyzed by ELISA, SDS-PAGE, and immunoblotting. Moreover, ELISA and flow cytometry techniques were designed using these mAbs to detect PRN in different strains of BP. RESULTS: Five mAbs were produced and selected based on their reactivity with native PRN. Our results demonstrate that purification of PRN by affinity chromatography resulted in a highly pure antigen with 75-85 percent recovery. In addition, ELISA and flow cytometry results indicated that these mAbs could recognize PRN in the bacterial cell walls of different BP strains. CONCLUSION: We successfully produced PRN-specific mAbs and designed an affinity chromatography method to purify PRN antigen with higher purity and recovery than conventional methods. These mAbs could be employed as valuable tools for the detection and purification of PRN for vaccine manufacturing.

Effect of Statins on the Blood Lipid Profile in Patients with Different Cardiovascular Diseases: A Systematic Review with Meta-analysis of Randomized Clinical Trials.

BACKGROUND: Statins are the main lipid-lowering drugs and are used in the prevention of cardiovascular diseases (CVDs). Since the results have been, to some extent, inconsistent in the clinical trials concerning different types of CVDs, a systematic review and meta-analysis was performed to prove the effect of statins on decreasing elevated levels of total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with CVDs. METHODS: Literature search was performed on major electronic databases (MEDLINE/ PubMed, Scopus, and ISI Web of Science) from inception up to July 2021 to find randomized controlled trials (RCTs) evaluating the effect of different statins on different types of CVDs. The effect size was determined using weighted mean difference (WMD) and corresponding 95% confidence interval (CI). RESULTS: Statin therapy significantly decreased levels of total cholesterol (WMD = -33.37 mg/dl, 95% CI: -45.98 to -20.76, P<0.001), LDL-C (WMD = -29.42 mg/dl, 95% CI: -36.81 to -22.03, P<0.001), and TG (WMD = -15.19 mg/dl, 95% CI = -26.41 to -3.97, P<0.001), and increased levels of HDL-C (WMD = 1.55 mg/dl, 95% CI: 0.20, to 2.90, P=0.02) in patients with different CVDs. CONCLUSION: Statin therapy was found effective in lowering levels of total cholesterol, LDL-C, and TG, and increasing levels of HDL-C in patients with different CVDs.

Notch signaling pathway: a comprehensive prognostic and gene expression profile analysis in breast cancer.

Breast cancer is a complex disease exhibiting a great degree of heterogeneity due to different molecular subtypes. Notch signaling regulates the differentiation of breast epithelial cells during normal development and plays a crucial role in breast cancer progression through the abnormal expression of the Notch up-and down-stream effectors. To date, there are only a few patient-centered clinical studies using datasets characterizing the role of Notch signaling pathway regulators in breast cancer; thus, we investigate the role and functionality of these factors in different subtypes using publicly available databases containing records from large studies. High-throughput genomic data and clinical information extracted from TCGA were analyzed. We performed Kaplan-Meier survival and differential gene expression analyses using the HALLMARK_NOTCH_SIGNALING gene set. To determine if epigenetic regulation of the Notch regulators contributes to their expression, we analyzed methylation levels of these factors using the TCGA HumanMethylation450 Array data. Notch receptors and ligands expression is generally associated with the tumor subtype, grade, and stage. Furthermore, we showed gene expression levels of most Notch factors were associated with DNA methylation rate. Modulating the expression levels of Notch receptors and effectors can be a potential therapeutic approach for breast cancer. As we outline herein, elucidating the novel prognostic and regulatory roles of Notch implicate this pathway as an essential mediator controlling breast cancer progression.

Effect of Statins on Serum level of hs-CRP and CRP in Patients with Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Several studies have reported that statins have anti-inflammatory effects. Nevertheless, results of clinical trials concerning the effect of statins on the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) have been inconsistent. Therefore, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the effect of statins on CRP and hs-CRP levels in patients with cardiovascular diseases (CVDs). METHODS: Literature search of the major databases was performed to find eligible RCTs assessing the effect of statins on serum levels of CRP and hs-CRP from the inception until the last week of April 2021. The effect sizes were determined for weighted mean difference (WMD) and 95% confidence intervals (CI). RESULTS: 26 studies were identified (3010 patients and 2968 controls) for hs-CRP and 20 studies (3026 patients and 2968 controls) for CRP. Statins reduced the serum levels of hs-CRP (WMD = -0.97 mg/L; 95% CI: -1.26 to -0.68 mg/L; P < 0.001) and CRP (WMD = -3.05 mg/L; 95% CI: -4.86 to -1.25 mg/L; P < 0.001) in patients with CVDs. Statins decreased the serum levels of hs-CRP in patients receiving both high-intensity and moderate/low-intensity treatments with these drugs. In addition, the duration of treatment longer than 10 weeks decreased hs-CRP levels. Only high-intensity statin treatment could marginally decrease serum levels of CRP in CVDs patients. CONCLUSIONS: This meta-analysis showed the efficacy of statins to reduce the concentrations of CRP and hs-CRP in patients with different types of CVDs.

Effect of statins on the plasma/serum levels of inflammatory markers in patients with cardiovascular disease; a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The anti-inflammatory properties of statins have been suggested by several researches. However, clinical trials have reported incongruous findings regarding the effect of statins on the levels of inflammatory markers other than high-sensitive C-reactive protein. Therefore, a systematic review and meta-analysis of randomized clinical trials were conducted to illuminate the effect of statins on serum levels of TNF-α, MCP-1, VCAM1, and IL-6 in patients with cardiovascular diseases (CVDs). METHODS: To find eligible studies, a systematic literature search of the main databases were conducted up to July 2021. The calculation of the effect sizes was conducted by standardized mean difference (SMD) and 95% confidence intervals (CI). RESULTS: The pooled analyses revealed that statins significantly reduced the TNF-α concentration (SMD = - 0.99 pg/mL; 95% CI - 1.43 to - 0.55 pg/mL; P < 0.001). Regarding dosage, high intensity (SMD = - 0.65 pg/mL; 95% CI - 1.19 to - 0.10, P = 0.02) and moderate/low (SMD = - 1.16 pg/mL; 95% CI - 1.84 to - 0.47, P = 0.001) intensity statins significantly decreased TNF-α levels. Moderate/low intensity statins administration in < 10 weeks treatment duration decreased serum level of TNF-α (SMD = - 0.91 pg/mL; 95% CI - 1.38 to - 0.44, P < 0.001). Lipophilic statins with high intensity dosage significantly decreased level of TNF-α (SMD = - 0.73 pg/mL; 95% CI - 1.43 to - 0.03, P = 0.04). Statins did not change serum levels of MCP-1, VCAM1, and IL-6 in CVD patients. CONCLUSIONS: The analyses indicated that statins have beneficial effects in decreasing serum levels of TNF-α in patients with CVDs.

Effect of curcumin on C-reactive protein as a biomarker of systemic inflammation: An updated meta-analysis of randomized controlled trials.

It has been suggested that curcumin is a potential agent for lowering the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP), as markers of inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin supplementation in lowering the concentrations of CRP and hs-CRP in patients with autoinflammatory conditions. Nine studies were found evaluating the effect of curcumin on CRP levels, while 23 studies were identified for hs-CRP. CRP concentration was decreased significantly compared to the placebo (WMD = -3.67 mg/L, 95% CI = -6.96 to -0.38, p = 0.02). There was a significant effect of curcumin at dose ≤1,000 mg/day on the CRP concentration. CRP concentration significantly decreased after >10-week intervention compared with placebo.hs-CRP concentration in the intervention group was significantly lower than that of placebo group. A significant effect of curcumin consumption was detected on the serum level of hs-CRP in studies with prescribing ≤1,000 mg/day, and those with ≤10-week duration of intervention. Curcumin consumption resulted in a reduction of hs-CRP in a non-linear fashion with stronger effects with less than 2000 mg curcumin per day. Curcumin seems to be beneficial in decreasing the hs-CRP and CRP levels in proinflammatory settings.

Effect of resveratrol on C-reactive protein: An updated meta-analysis of randomized controlled trials.

We conducted a meta-analysis on the available randomized clinical trials (RCTs) to assess the role of resveratrol in lowering C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels, as markers of inflammation, in various inflammatory disorders. Literature search through Medline/PubMed, Scopus, ISI Web of Science, and Cochrane Library yielded 35 RCTs (24 studies for hs-CRP and 11 studies for CRP). Pooled results revealed that resveratrol supplementation significantly reduced the hs-CRP (MWD = -0.40 mg/L; 95% CI: -0.70 to -0.09 mg/L; p = .01) and CRP (MWD = -0.31 mg/L; 95% CI: -0.47 to -0.15 mg/L; p < .001) levels in serum. Subgroup analysis revealed that resveratrol in group with ≥10 weeks significantly reduces hs-CRP levels (MWD = -0.48 mg/L; 95% CI: -0.92 to -0.04 mg/L; p = .03) and CRP (WMD = -0.47 mg/L, 95% CI = -0.69 to -0.25, p < .001). A dose of ≥500 mg/day supplementation improves the levels of CRP, but not hs-CRP. This meta-analysis demonstrates that resveratrol consumption is effective in lowering the levels of CRP and hs-CRP in inflammatory conditions, especially if supplementation takes place for ≥10 weeks with ≥500 mg/day.

Vitamin D Receptor gene polymorphisms and susceptibility to type 2 diabetes: evidence from a meta-regression and meta-analysis based on 47 studies.

BACKGROUND: Evidence from various studies suggest that vitamin D receptor (VDR) gene polymorphisms are associated with type 2 diabetes (T2D); However, these results have been disputable. Here we conducted a meta-analysis to comprehensively evaluate the effect of VDR gene polymorphisms and susceptibility to T2D. METHODS: All relevant studies reporting the association between VDR gene polymorphisms and susceptibility to T2D published up to August 2020 were identified by comprehensive systematic database search in web of science, Scopus, and Medline. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure strength of association. The methodological quality of each study was assessed according to the Newcastle-Ottawa Scale. Subgroup and meta-regression analysis were also performed. RESULTS: A total of 47 case-control studies were included in this meta-analysis. The overall population results revealed a significant association between FokI, and BsmI (heterozygote model) polymorphisms and T2D in the overall analysis. However, no association was found with the TaqI and ApaI polymorphisms. Moreover, the pooled results of subgroup analysis by ethnicity suggested significant association between FokI, TaqI, and BsmI polymorphisms and T2D in some subgroups. Meta-regression analyses indicated that none of the publication year, ethnicity, and genotyping method were the source of heterogenicity in all four polymorphisms. CONCLUSIONS: This meta-analysis suggested a significant association between VDR gene FokI, and BsmI (heterozygote model) polymorphisms and T2D susceptibility in overall population and ethnic-specific analysis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-020-00704-z.

Effect of resveratrol on inflammatory cytokines: A meta-analysis of randomized controlled trials.

The aim of the current study was to perform a meta-analysis of randomized clinical trials regarding the effect of resveratrol in decreasing the levels of inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α in a combination of inflammatory diseases. Literature search was carried out in Scopus, ISI web of science, Medline, and Cochrane Library databases by up to September 2020. The pooled effect size was determined through measuring the weighted mean differences (WMD) and their corresponding 95% confidence intervals (CI) for the difference between the resveratrol-receiving and control groups. Finally, 33 publications, including 3 studies on IL-1, 26 studies on IL-6, 4 studies on IL-8, and 21 studies on TNF-α met our final inclusion criteria and included in the quantitative analysis. Analysis in the overall population showed a significant effect of resveratrol consumption in reducing serum TNF-α levels (WMD = -0.66 pg/ml, 95% CI = -1.05 to -0.27, P = 0.001). A significant reduction of IL-6 concentration was observed only in the patients receiving ≥500 mg/day dose of resveratrol (WMD = -1.89 pg/ml, 95% CI = -3.73 to -0.05, P = 0.04) with inter-study heterogeneity (I2 = 94.4%, P < 0.001). Nonetheless, no significant alteration was observed in IL-1 (WMD = -0.14 pg/ml, 95% CI = -0.31 to 0.03, P = 0.10) and IL-8 (WMD = 0.18 pg/ml, 95% CI = -1.04 to 1.40, P = 0.73) levels following resveratrol consumption. Based on the present findings, resveratrol is able to decrease TNF-α and IL-6 (in ≥500 mg/day dose) levels but not IL-1 and IL-8 levels.

Effect of curcumin on proinflammatory cytokines: A meta-analysis of randomized controlled trials.

It has been suggested that curcumin has the potential for lowering inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin/turmeric supplementation in reducing concentrations of interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α in patients with an inflammatory background. The main databases were searched to identify eligible trials evaluating the effect of curcumin in reducing IL-1, IL-6, IL-8, and TNF-α in serum up to March 2021. The effect sizes for weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated. Overall, 32 randomized controlled trials (RCTs) were included. There was a significant decrease in the serum levels of IL-1 (WMD = -2.33 pg/ml, 95% CI = -3.33 to -1.34, P < 0.001) and TNF-α (WMD = -1.61 pg/ml, 95% CI = -2.72, -0.51, P < 0.001) compared to the placebo group following treatment. Nonetheless, curcumin/turmeric supplementation was non-significantly associated with reduced levels of IL-6 (WMD = -0.33 pg/ml, 95% CI = -0.99-0.34, P = 0.33) and increased levels of IL-8 (WMD = 0.52 pg/ml, 95% CI = -1.13-2.17, P = 0.53). The dose-responses analysis indicated that curcumin/turmeric supplementation resulted in IL-1 and IL-8 alteration in a non-linear model. Subgroup analysis according to duration and dose of treatment and target population revealed diverse outcomes. Curcumin could have a beneficial effect in reducing the proinflammatory cytokines IL-1 and TNF-α, but not IL-6 and IL-8 levels.

Interleukin-10 Gene Promoter Polymorphisms and Susceptibility to Asthma: Systematic Review and Meta-analysis.

Several studies have previously assessed the association between interleukin (IL)-10 gene polymorphisms and the risk of asthma, leading to conflicting results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis of the IL-10 gene rs1800896, rs1800871, and rs1800872 single-nucleotide polymorphisms (SNPs) and susceptibility to asthma. A systematic literature search performed until April 2020, and the pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated to determine the association strength. Thirty articles comprising 5678 asthmatic patients and 6079 controls met the inclusion criteria. No significant association was found between rs1800872 SNP and susceptibility to asthma across all genetic models in the overall and subgroup analyses. The rs1800871 SNP had only significant association with a decreased risk of asthma in Europeans (OR 0.66, CI 0.53-0.82, P < 0.001). However, rs1800896 SNP was significantly associated with a decreased risk of asthma by dominant (OR 0.67, CI 0.50-0.90, P < 0.001) and heterozygote (OR 0.66, CI 0.49-0.88, P < 0.001) models in the overall analysis. Subgroup analyses indicated significant association of rs1800896 SNP by dominant (OR 0.45, CI 0.28-0.72, P < 0.001) and heterozygote (OR 0.43, CI 0.26-0.70, P < 0.001) models in the African population. The IL-10 rs1800896 SNP confers protection against the risk of asthma, especially in Africans. Additionally, rs1800871 SNP has a protective role against asthma in Europeans.

Association between IL7 Receptor Alpha (Il7ra) gene rs6897932 polymorphism and the risk of Multiple Sclerosis: A meta-regression and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we aimed to find a consistent conclusion for the association between the interleukin 7 receptor alpha (IL7RA) gene rs6897932 single nucleotide polymorphism (SNP) and multiple sclerosis (MS) risk. METHODS: Here, we performed a comprehensive systematic search in PubMed, Scopus, and Web of Science to find relevant studies published before November 2020 investigating the association between rs6897932 SNP and MS risk. In the pooled analysis, we determined the odds ratio (OR) and the corresponding 95% confidence interval (CI) for the association level between rs6897932 SNP and the risk of MS. RESULTS: In the current meta-analysis 33 case-control studies (30 articles) containing 19351 patients and 21005 healthy controls certify the inclusion criteria. According to the pooled analysis, a statistically significant association of IL7RA gene rs6897932 SNP with MS risk was found across recessive model (OR= 0.84, 95% CI= 0.77-0.92, P< 0.001, FEM), allelic model (OR= 0.91, 95% CI= 0.85-0.99, P= 0. 02, REM), TT vs. CC model (OR= 0.79, 95% CI= 0.67-0.93, P= 0.005, REM). Moreover, the subgroup analysis based on the ethnicity indicated a negative significant association in Europeans; dominant model (OR= 0.88, 95% CI= 0.78-1.01, P= 0.06, REM), recessive model (OR= 0.79, 95% CI= 0.71-0.88, P< 0.001, REM), allelic model (OR= 0.88, 95% CI= 0.81-0.96, P= 0.003, REM), TT vs. CC model (OR= 0.74, 95% CI= 0.61-0.88, P<0.001, REM) models. Nonetheless, no significant association was detected in Asians and Americans. CONCLUSIONS: IL7RA gene rs6897932 SNP decreases MS susceptibility in overall population and Europeans.

Vitamin D Receptor Gene Polymorphisms and the Risk of Metabolic Syndrome (MetS): A Meta-Analysis.

BACKGROUND: Several studies have assessed the association between the vitamin D receptor (VDR) polymorphism and the risk of metabolic syndrome (MetS). However, the results were inconsistent and inconclusive. Therefore, we conducted a meta-analysis to clarify the exact association between the vitamin D receptor (VDR) polymorphisms and the risk of MetS. METHODS: All accessible studies reporting the association between the FokI (rs2228570) or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232 polymorphisms of the Vitamin D Receptor and susceptibility to MetS published prior to February 2019 were systematically searched in Web of Science, Scopus, and PubMed. After that, Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to evaluate the strength of the association in five genetic models. RESULTS: A total of 9 articles based on four gene variations, and comprising 3348 participants with 1779 metabolic syndrome patients were included. The overall results suggested a significant association between BsmI (rs1544410) polymorphism and MetS susceptibility in recessive model (OR, 0.72, 95% CI, 0.55-0.95, fixed effect model), allelic model (OR, 0.83, 95% CI, 0.72-0.95, fixed effect model), and bb vs BB (OR, 0.65, 95% CI, 0.46-0.93, fixed effect). However, no significant association was identified between TaqI (rs731236) polymorphism, ApaI (rs7975232) polymorphism, and FokI (rs2228570) polymorphism and MetS. CONCLUSION: This meta-analysis suggested an association between the BsmI (rs1544410) polymorphism and MetS. Indeed, BsmI (rs1544410) acts as a protective factor in the MetS. As a result, the VDR gene could be regarded as a promising pharmacological and physiological target in the prevention or treatment of the MetS.

Interleukin-4 gene polymorphism (C33T) and the risk of the asthma: a meta-analysis based on 24 publications.

BACKGROUND: Previous studies evaluated the association of IL-4 C33T polymorphism and risk of bronchial asthma but failed to establish a consistent conclusive association. In the present meta-analysis, we intend to define a more reliable estimate of the association in the presence of filling published literature. METHODS: An exhaustive search in Web of Science, Scopus, and PubMed databases was performed to identify all relevant publications before September 2020, and 24 publications (28 studies) with 6587 cases and 8408 controls were included in final analysis. The association between polymorphism and risk of asthma were measured by Odd ratios (ORs) and 95% confidence intervals (CIs). Moreover, Cochran's Q and the I2 statistics were used to evaluate the degree of heterogeneity between studies. RESULTS: In the overall study populations, a significant positive association was detected under all genotype models and announced the IL-4 C33T polymorphism as a potential risk factor in the pathogenesis of asthma. In the subgroup analysis by age, a significant association between IL-4 C33T polymorphism and risk of asthma in different age groups was identified in allelic model, which highlighted the predisposing role of the T allele for the asthma risk in all three age groups. Furthermore, the results of subgroup analysis by continent were heterogenous. Accordingly, IL-4 C33T polymorphism was a risk factor in Europeans (all models except heterozygote comparison), Americans (all models except recessive and homozygote comparison) and Asians (just recessive and allelic model). Finally, the ethnicity-specific analysis disclosed a significant association between IL-4 C33T polymorphism and asthma risk in Caucasians (all genotype models except heterozygote comparison), while this association was not significant in African-Americans. CONCLUSIONS: This study suggests that IL-4 C33T polymorphism potentially acts as a risk factor for asthma in different ethnicities and age groups.

Interleukin 4 gene polymorphism (-589C/T) and the risk of asthma: a meta-analysis and met-regression based on 55 studies.

BACKGROUND: Numerous investigations have previously evaluated the association of interleukin (IL) 4 gene polymorphisms and the risk of asthma, conferring inconsistent results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis of IL4 gene -589C/T (rs2243250) polymorphism and susceptibility to asthma. METHODS: A systematic literature search was performed in ISI web of science, Scopus, Medline/PubMed databases prior to September 2020, and the pooled odds ratio (OR) and their corresponding 95% CI were calculated to determine the association strength. RESULTS: Literature search led to retrieving of 49 publications (55 case-control studies) containing 9572 cases and 9881 controls. It was revealed that IL4 gene -589C/T polymorphism increased the risk of asthma across all genetic models, including dominant model (OR = 1.22), recessive model (OR = 1.17), allelic model (OR = 1.21), and TT vs. CC model (OR = 1.34), but not the CT vs. TT model. The subgroup analysis by age indicated that IL4 gene -589C/T polymorphism was significantly associated with asthma risk in both pediatrics and adults. Additionally, the subgroup analysis by ethnicity revealed significant association in Asian, American, and Europeans. Finally, subgroup analysis by East Asian and non-East Asian populations indicated significant associations. CONCLUSIONS: The current meta-analysis revealed that IL4 gene -589C/T polymorphism was a susceptibility risk in both pediatrics and adults in the whole and different ethnic groups.