ATP2B1 gene polymorphisms rs2681472 and rs17249754 are associated with susceptibility to hypertension and blood pressure levels: A systematic review and meta-analysis

Objective:The present study aimed to conduct a systematic review and meta-analysis to evaluate the relationships between ATP2B1 gene polymorphisms with blood pressure (BP) level and susceptibility to hypertension.Methods:PubMed, Web of Science, Embase and China National Knowledge Infrastructure (CNKI) Databases were systematically searched by 2 independent researchers to screen studies on ATP2B1 gene polymorphisms and BP related phenotypes. The records retrieval period was limited from the formation of the database to March 4, 2021. Pooled odds rations (ORs) or β and their 95% confidence intervals (95%CI) were calculated to assess the association between ATP2B1 gene polymorphisms and the risk of hypertension or BP levels. Publication bias and sensitivity analysis were conducted to find potential bias. All the statistical analysis were conducted with Stata version 11.0 software.Results:A total of 15 articles were ultimately included in the present study, including 15 polymorphisms of ATP2B1 gene. Nine articles (N = 65,362) reported the polymorphism rs17249754, and 7 articles(N = 91,997) reported rs2681472 (both loci were reported in 1 article). Meta-analysis showed that rs17249754 (G/A) and rs2681472 (A/G) were associated with the susceptibility to hypertension (rs17249754: OR = 1.19, 95%CI: 1.10–1.28; rs2681472: OR = 1.15, 95%CI: 1.12–1.17), and were positively associated with systolic BP (SBP) and diastolic blood pressure (DBP) (rs17249754: SBP, β=1.01, 95%CI: 0.86–1.16, DBP, β=0.48, 95%CI: 0.30–0.66; rs2681472: SBP, β=0.92, 95%CI: 0.77–1.07, DBP, β=0.50, 95%CI: 0.42–0.58) in the additive genetic model. Subgroup analysis stratified by race, population, sample size, and BP measurement method revealed that the association between A allele in rs2681472 polymorphism and risk of hypertension was slightly stronger in European (EUR) populations (OR = 1.16, 95%CI: 1.13–1.20) than in East Asians (OR = 1.14, 95%CI: 1.10–1.17). While in East Asians, relation between rs17249754 with risk of hypertension (OR = 1.19, 95%CI: 1.10–1.28) is stronger than rs2681472 (OR = 1.14, 95%CI: 1.10–1.17).Conclusions:Our study demonstrated that ATP2B1 gene polymorphism rs2681472 and rs17249754 were associated with BP levels and the susceptibility to hypertension.     

Association between MMP-2 gene polymorphism and cataract susceptibility: A protocol for systematic review and meta-analysis

Background:Matrix metalloproteinase-2 (MMP-2) polymorphisms have been considered as risk factors of cataracts, but the results still remain controversial. In this study, we have performed a systematic meta-analysis to evaluate the association between MMP-2 polymorphisms and cataract risks.Methods:Published literature was retrieved from Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases. The case–control studies that explored the association between MMP-2 polymorphisms and cataract risks were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model.Results:This study could provide high-quality and evidence-based medical evidence for the correlation between MMP-2 polymorphisms and cataract risksConclusion:The study could provide updated evidence for the evaluation of the relationship between MMP-2 polymorphism and cataract risk.Ethics and dissemination:The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.OSF Registration Number:DOI 10.17605/OSF.IO/KU9NE.     

Relationship between thrombomodulin gene polymorphism and susceptibility to venous thromboembolism: A protocol for systematic review and meta-analysis

Background:Previous studies displayed that thrombomodulin gene polymorphisms are closely associated with venous thromboembolism (VTE), while the results are inconsistent. Therefore, we conducted a meta-analysis to accurately determine the association between thrombomodulin gene polymorphism and the risk of VTE.Methods:Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, EmBase, and Web of Science databases were searched, and the time to build the database was set until January 2021. The association between thrombomodulin gene polymorphism and the risk of VTE was evaluated. Meta-analysis was performed with STATA 16.0 software, and the odds ratio and its 95% confidence interval were applied to estimate the relationship between thrombomodulin gene polym‘orphism and the risk of VTE.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion:This meta-analysis will summarize the relationship between thrombomodulin genepolymorphism and VTE risk.Ethics and dissemination:Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations.OSF REGISTRATION NUMBER:DOI 10.17605/OSF.IO/UEHJP.     

Calcineurin regulates the stability and activity of estrogen receptor α

Estrogen receptor α (ER-α) mediates estrogen-dependent cancer progression and is expressed in most breast cancer cells. However, the molecular mechanisms underlying the regulation of the cellular abundance and activity of ER-α remain unclear. We here show that the protein phosphatase calcineurin regulates both ER-α stability and activity in human breast cancer cells. Calcineurin depletion or inhibition down-regulated the abundance of ER-α by promoting its polyubiquitination and degradation. Calcineurin inhibition also promoted the binding of ER-α to the E3 ubiquitin ligase E6AP, and calcineurin mediated the dephosphorylation of ER-α at Ser²⁹⁴ in vitro. Moreover, the ER-α (S294A) mutant was more stable and activated the expression of ER-α target genes to a greater extent compared with the wild-type protein, whereas the extents of its interaction with E6AP and polyubiquitination were attenuated. These results suggest that the phosphorylation of ER-α at Ser²⁹⁴ promotes its binding to E6AP and consequent degradation. Calcineurin was also found to be required for the phosphorylation of ER-α at Ser¹¹⁸ by mechanistic target of rapamycin complex 1 and the consequent activation of ER-α in response to β-estradiol treatment. Our study thus indicates that calcineurin controls both the stability and activity of ER-α by regulating its phosphorylation at Ser²⁹⁴ and Ser¹¹⁸. Finally, the expression of the calcineurin A–α gene (PPP3CA) was associated with poor prognosis in ER-α–positive breast cancer patients treated with tamoxifen or other endocrine therapeutic agents. Calcineurin is thus a promising target for the development of therapies for ER-α–positive breast cancer.

Estrogen receptor α (ER-α) plays a central role in the proliferation of breast cancer cells by increasing the expression of oncogenes, such as those encoding cyclin D1 and c-Myc (1). The expression and activity of ER-α are increased in >70% of breast cancer cases, and the receptor is targeted by drugs such as tamoxifen (2, 3). A substantial proportion of ER-α–positive breast cancer cells become resistant to anti‐estrogens, however, resulting in the progression of the disease. The mechanisms by which the cancer cells acquire resistance to these agents include the generation of splice variants of ER-α, the mutation of the ER-α gene (ESR1), and changes in stability of the ER-α protein (4).Increased protein stability appears to be a key contributor to the up-regulation of ER-α in breast cancer. The ubiquitination of ER-α is one mechanism responsible for ER-α degradation. Several E3 ligases that mediate the degradation of ER-α have been identified and include E6-associated protein (E6AP) (5), carboxyl terminus of Hsp70-interacting protein (CHIP) (6), breast cancer type 1 (BRCA1) (7), BRCA1-associated RING domain 1 (8), S phase kinase–associated protein 2 (SKP2) (9), and mouse double minute 2 homolog (10). On the other hand, other E3 ligases—such as RING finger protein (RNF) 31, shank-associated RH domain–interacting protein, and RNF8 (11–13)—have been shown to promote ER-α signaling by stabilizing ER-α protein.The residues Lys³⁰² and Lys³⁰³ of ER-α are targeted for ubiquitination (14). The ubiquitination of ER-α is associated with its phosphorylation, with several kinases such as cyclin-dependent kinase (CDK) 11 (15), Src (5), protein kinase C (16), p38 mitogen-activated protein kinase (9), and extracellular signal–regulated kinase 7 (17) having been shown to phosphorylate the protein. The phosphorylation of ER-α at Ser²⁹⁴ has thus been related to its ubiquitination by SKP2 (9), with the Ser²⁹⁴-phosphorylated form of ER-α being a preferred substrate for ubiquitination by SKP2 in vitro. However, the expression level of ER-α was found to be unaltered in cells depleted of SKP2, suggesting that other E3 ligases may contribute to the degradation of ER-α subsequent to its phosphorylation at Ser²⁹⁴.Calcium is an important regulator of signaling pathways that control oncogenesis and cancer progression, and Ca²⁺ signaling has been linked to signaling by ER-α. β-estradiol (E2) has been shown to induce rapid Ca²⁺ influx in cells, and the Ca²⁺-binding protein calmodulin interacts with ER-α, increases its stability, and modulates E2-regulated gene expression (18). Calcineurin is a Ca²⁺/calmodulin-activated serine–threonine phosphatase that plays a major role in the regulation of immediate cellular responses and gene expression by Ca²⁺ signaling (19). It is also a target of immunosuppressive drugs administered in clinical practice, such as cyclosporine A and FK506. Calcineurin is composed of two subunits: a catalytic subunit, designated calcineurin A, that is encoded by three genes (PPP3CA, PPP3CB, and PPP3CC), and a regulatory subunit, designated calcineurin B, that is encoded by two genes (PPP3R1 and PPP3R2).In the present study, we found that calcineurin plays a previously unrecognized role as a positive regulator of the stability and activity of ER-α in breast cancer cells by mediating its dephosphorylation at Ser²⁹⁴, as well as the activation of mechanistic target of rapamycin complex 1 (mTORC1) and the consequent phosphorylation of ER-α at Ser¹¹⁸, respectively. Furthermore, a high-expression level of PPP3CA was associated with poor prognosis in a subset of breast cancer patients, suggesting that the selective inhibition of calcineurin might be an effective approach to the treatment of ER-α–positive breast cancer.     

Lack of Association Between Transforming Growth Factor Beta 1 -509C/T and +915G/C Polymorphisms and Chronic Hepatitis B in Iranian Patients

Background:

Chronic hepatitis B is one of the world''s major health concern. The etiological agent of this infection is hepatitis B virus (HBV), which can evade the immune system response. Transforming growth factor beta 1 (TGF-β1) can act against HBV by suppressing the viral replication. The TGF-β1 also plays an important role in preventing liver damage in chronically HBV infected patients.

Objectives:

In this study, the association of TGF-β1 +915G/C and -509C/T gene polymorphisms with chronic hepatitis B was evaluated in Iranian patients.

Materials and Methods:

A population-based case–control study was conducted in Taleghani Hospital, Tehran. A number of 220 patients with chronic hepatitis B and the same number of healthy control subjects were designated the case and the control groups. The PCR-Restriction Fragment Length Polymorphism Method (PCR-RFLP) method was used for genotyping both polymorphisms. Ten percent of the control samples were sequenced to confirm the results.

Results:

No statically significant differences in genotype distribution and allele frequency were observed for both polymorphisms between healthy controls and patients with chronic hepatitis B.

Conclusions:

There was no association between TGF-β1 -509C/T and +915G/C polymorphisms with chronic hepatitis B and it seems that these changes don not play a significant role in increasing the risk of chronic infection in Iranian patients.     

Effect of electroacupuncture on postoperative cognitive dysfunction for patients undergoing total knee arthroplasty: A protocol for systematic review and meta-analysis of randomized controlled trials

Background:Electroacupuncture is increasingly used in rehabilitation for postoperative cognitive dysfunction (POCD), but relevant evidence remains unclear for patients receiving total knee arthroplasty (TKA).Methods:The databases research of PubMed, EMBASE, CINAHL, and China National Knowledge Infrastructure (CNKI) will be conducted from inception to December 31, 2020. The relevant randomized controlled trials (RCTs) from data will be screened one by one. The remaining studies that meet the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software. Paired 2 reviewers will assess quality of the included studies and publication bias by using the Cochrane Collaboration risk of bias tool, and Egger test and Begg test respectively. And grading of recommendations assessment, development and evaluation (GRADE) will be used to estimate the quality of evidence.Results:In this study, we will analyze the effect of electroacupuncture on Mini-Mental State Examination (MMSE), interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), S100-β protein, and adverse events for patients with TKA.Conclusion:Our findings will provide evidence for the effectiveness of electroacupuncture on the treatment and prevention of POCD for TKA patients.Registration number:Available at: https://osf.io/azyt9 (DOI number: 10.17605/OSF.IO/AZYT9).     

Effects of α lipoic acid combined with olmesartan medoxomil on blood glucose and oxidation indicators in patients with diabetic nephropathy: A protocol for a parallel,randomized, double-blind,controlled clinical trial

Background:Diabetic nephropathy (DN) is a common microvascular complication of diabetes, which poses a serious threat to the health and life of patients. There is evidence that both α lipoic acid and olmesartan medoxomil have positive effects in the treatment of DN, but whether the 2 have synergistic effects and the effects on blood glucose and oxidation indicators are controversial.Methods:This is a prospective parallel, randomized, double-blind, placebo-controlled trial to study the effects of α lipoic acid in combination with olmesartan medoxomil on blood glucose and oxidation indicators in patients with DN. Participants will be randomly assigned to a treatment group, which will receive α lipoic acid dispersive tablets combined with olmesartan medoxomil tablets, or a control group, which will receive olmesartan medoxomil tablets combined with placebo for 4 weeks, followed up for 12 weeks. Observation indicators include: glycemic indicators [fasting blood glucose, 2 hours postprandial blood glucose and glycosylated hemoglobin], the oxidation indicators [serum glutathione, superoxide dismutase, malondialdehyde, 8-hydroxydeox-yguanosine], and adverse reactions. Finally, SPASS 22.0 software will be used for statistical analysis of the data.Discussion:This study will evaluate the effects of α lipoic acid combined with olmesartan medoxomil on blood glucose and oxidation indicators in patients with DN. The results of this study will provide a reference for the clinical use of α lipoic acid combined with olmesartan medoxomil in the treatment of DN.Trial registration:OSF Registration number: DOI 10.17605/OSF.IO/VJWXS     

Effects of SCN1A and SCN2A polymorphisms on responsiveness to valproic acid monotherapy in epileptic children: A protocol for systematic review and meta-analysis

Background: The gene mutation of coding sodium channel is one of the most important mechanisms in the pathogenesis of epilepsy. There exists a large inter-individual variation in the efficacy of valproic acid (VPA) against epilepsy. What are the genetic polymorphism influences of sodium channels on VPA response is still under discussion. In this study, a meta-analysis was used to further explore the effects of SCN1A and SCN2A gene polymorphism on VPA response in children with epilepsy.Methods: The PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology Medicine disc, and Wan Fang Database were searched up to April 2021 for appropriate studies regarding the association between SCN1A and SCN2A gene polymorphism on VPA response in children suffering from epilepsy. The meta-analysis was conducted by Review Manager 5.3 software.Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion: This meta-analysis will summarize the effects of SCN1A and SCN2A gene polymorphisms on VPA response in children with epilepsy.OSF Registration Number:DOI 10.17605/OSF.IO/N2786.     

Correlation between epidermal growth factor receptor mutations and nuclear expression of female hormone receptors in non-small cell lung cancer: a meta-analysis

Background

Compared with male, female non-small cell lung cancer (NSCLC) patients have better response when treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), suggesting a potential association between female hormones and EGFR mutation. However, the results provided by previous studies were inconclusive and controversial. We sought to examine the link between the expression of nuclear female hormone receptors and EGFR mutations in NSCLC.

Methods

Electronic databases were used to search the relevant articles. The involved hormone receptors included estrogen receptor (ER) and progesterone receptor (PR). The primary endpoint was the occurrence of ER/PR expression and EGFR mutation in NSCLC patients.

Results

Five studies fulfilled the criteria and were included in our analysis. Patients with high ER-β expression had higher positive EGFR mutation than low ER-β patients (44.2% vs. 23.7%), and there was a significant difference between the two groups [odds radio (OR) 3.44, 95% confidence interval (CI): 2.40-4.93, Z=6.72, P<0.001]. However, there is no significant correlation between EGFR mutations and ER-α (when included ER-α3, OR 1.20, 95% CI: 0.62-2.33, Z=0.55, P=0.58; and when included ER-α4, OR 1.18, 95% CI: 0.62-2.25, Z=0.51, P=0.61) or PR (OR 1.29, 95% CI: 0.40-4.10, Z=0.43, P=0.67). No significant publication bias was observed.

Conclusions

High nuclear expression of ER-β, but not ER-α or PR is correlated with EGFR mutations in NSCLC. The underlying mechanism and potential translational relevance warrant further investigation.     

Association between vitamin D receptor polymorphisms and acute pancreatitis: A protocol for systematic review and meta analysis

Background:Several studies have been performed to investigate the association between vitamin D receptor (VDR) gene polymorphism and acute pancreatitis, but the results are inconclusive. We conducted this meta-analysis for a precise estimation of the association between BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and FokI (rs2228570) polymorphisms and acute pancreatitis.Methods:Appropriate studies were retrieved by searching Web of Science, PubMed, Scopus, and Google scholar databases, until January 31, 2021. Two reviewers independently conducted data extraction and literature quality evaluation. Odds ratios and 95% confidence intervals were calculated to evaluate the strength of the association.All of the data were analyzed with Stata 16.0.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusions:This meta-analysis will summarize the association between BsmI, ApaI, TaqI, and FokI polymorphisms and the risk of acute pancreatitis.Ethics and dissemination:Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms.OSF REGISTRATION NUMBER:DOI 10.17605/OSF.IO/83W7R.     

Efficacy and safety of ulinastatin on cognitive dysfunction after general anesthesia in elderly patients: A protocol for systematic review and meta-analysis

Background:With the aging of society, the incidence of diseases increases. And along with the increase of surgery rate, the number of elderly patients with postoperative cognitive dysfunction (POCD) is also increasing. POCD seriously affects the mental state and quality of life of patients and their families. Clinical studies have shown that POCD is closely related to inflammatory reaction, and Ulinastatin can inhibit the inflammatory reaction and reduce the incidence of POCD in elderly patients under general anesthesia. However. the effect of Ulinastatin on POCD in elderly patients under general anesthesia has not been systematically evaluated.Objective:Meta analysis will be used to evaluate the efficacy and safety of Ulinastatin in elderly patients with general anesthesia POCD during perioperative period.Methods:We will search China Science and Technology Journal Database Chinese database, China National Knowledge Infrastructure, Wanfang, China biomedical database, PubMed, EMBASE, Cochrane Library and web of science for randomized controlled trials of the effect of Ulinastatin on POCD of elderly patients with general anesthesia from the establishment of the database to November 2020. The 2 researchers will independently screen the literature and conducted quality assessment and data extraction for the included studies, Revman5.3 software will be used for risk assessment and meta analysis.Results:In this study, the efficacy and safety of Ulinastatin in elderly patients with general anesthesia POCD will be evaluated by the incidence of postoperative cognitive impairment, mini mental state examination (Mini-Mental State Examination [MMSE]), visual regeneration, associative memory score, S100 β protein, tumor necrosis factor α (TNF- α), interleukin 6 (IL-6), IL- 10 inflammatory factors and the incidence of adverse reactions.Conclusion:The use of Ulinastatin in perioperative period can significantly reduce the inflammatory level of elderly patients after general anesthesia, effectively prevent the occurrence of POCD and reduce its incidence.Ethics and dissemination:The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.OSF Registration number:DOI 10.17605/OSF.IO/GY3V7     

Association of chronic rhinosinusitis with bronchial asthma and its severity: A protocol for systematic review and meta-analysis

Background:To explore the association of chronic rhinosinusitis (CRS) with bronchial asthma (BA) as well as its severity.Methods:A comprehensive database search will be performed from PubMed, Embase, Cochrane Library, and Web of science for related literatures. Heterogeneity test will be used to assess each outcome indicator. If heterogeneity statistics I² ≥ 50%, the random effects model will be applied; if I² < 50%, the fixed effects model will be performed. Sensitivity analysis will be performed in all models. STATA 15.0 software (Stata Corporation, College Station, TX) will be used for statistical analysis. Risk ratio (RR) will be used as the effect size for enumeration data. P < .05 is considered statistically significant.Conclusion:This study will evaluate the association of CRS with the prevalence of BA as well as its severity.OSF registration number:10.17605/OSF.IO/GCTM9.     

Association of cytochrome P450 2C19 polymorphisms with coronary heart disease risk: A protocol for systematic review and meta analysis

Background:Polymorphisms in the cytochrome P450 2C19 (CYP2C19) gene have been reported to be associated with coronary heart disease (CHD), but the results were not consistently analyzed among different patient groups. To derive a more precise estimation of these associations, we will conduct a meta-analysis to investigate the polymorphisms of CYP2C19 in all published studies.Methods:Electronic databases (Google Scholar, ISI Web of Science, Pubmed, Embase, China National Knowledge Infrastructure, Wanfang, and China Biological Medicine) will be used to search clinical case-control or cohort studies about CYP2C19 polymorphism and CHD published until November 2020. Two reviewers will independently select the study, extract the data, and evaluate the quality of the study. Odds ratios with 95% confidence interval will be used to evaluate the strength of the association between the CYP2C19 polymorphism and CHD susceptibility under 4 genetic models. Subgroup analysis will be conducted by different ethnicity and genotyping method. Sensitivity analysis will be performed via sequentially omitting each of the included studies 1 at a time. Begg funnel plots and Egger test will be used to examine the potential publication bias. All the statistical analyses will be performed using Review Manager 5.3 and Stata 12.0.Results:This study will provide a better understanding of the association between CYP2C19 polymorphisms and coronary heart disease risk.Conclusion:The publication of this protocol will minimize the possibility of bias due to post hoc changes to the analysis protocol, thus helping to obtain reliable evidence.OSF registration number:DOI 10.17605/OSF.IO/R7U93     

The association of OPG polymorphisms with risk of osteoporotic fractures: A systematic review and meta-analysis

Background:Subjects with low bone mineral density and osteoporosis are more likely to suffer osteoporotic fractures during their lifetime. Polymorphisms in osteoprotegerin (OPG) gene are found to be associated with low bone mineral density and osteoporosis risk but their association with fracture risk is inconclusive. Here, we performed a meta-analysis to investigate the relationship between OPG polymorphisms with susceptibility to osteoporotic fractures.Methods:Eligible studies investigating the association between common OPG polymorphisms (A164G, T245G, T950C, and G1181C) and risk of osteoporotic fracture were retrieved from PubMed, EMBASE, Web of Science, and the Cochrane Library. Odds ratio (OR) and the 95% confidence interval (CI) were calculated in the allelic, dominant, recessive, and homozygous model. Subgroup analyses of vertebral fractures, Caucasians, and postmenopausal women were also performed.Results:A total of 14 studies comprising 5459 fracture cases and 9860 non-fracture controls were included. A163G was associated with fracture risk in dominant (OR = 1.29, 95%CI 1.11–1.50), recessive (OR = 1.64, 95%CI 1.10–2.44), and homozygous model (OR = 1.73, 95%CI 1.16–2.59). T245G was significantly correlated with susceptibility to fractures in all genetic models. Subjects with CC genotype of T950C had a reduced risk of fracture compared to those with CT or TT genotypes (OR = 0.81, 95%CI 0.70–0.94, P = .004). Subgroup analysis showed that A163G and T245G but not T950C and G1181C were associated with vertebral fracture risk.Conclusion:OPG A163G and T245G polymorphisms were risk factors of osteoporotic fractures while T950C had a protective role. These polymorphisms can be used as predictive markers of fractures.     

Association of vitamin D receptor gene polymorphism with type 1 diabetes mellitus risk in children: A protocol for systematic review and meta-analysis

Background:Recent genetic association studies showed that there are contradictory results on the relationship between vitamin D receptor (VDR) gene polymorphisms and type 1 diabetes mellitus (T1DM) risk in children. The purpose of this systematic review is to collect the currently available evidence to evaluate the relationship between VDR gene polymorphisms and the risk of T1DM in children.Methods:Such medical databases as Wanfang Data, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science were extensively searched for relevant literatures published before June 2021 with the focus on the relationship between VDR gene polymorphisms and the risk of T1DM in children. The risk of bias was evaluated as per the Newcastle-Ottawa Scale by 2 independent researchers. Meta-analysis was performed to quantify the relationship between VDR gene polymorphisms and T1DM risk in children.Results:The results of this meta-analysis would be submitted to a peer-reviewed journal for publication.Conclusion:The relationship between VDR gene polymorphisms and T1DM risk in children is explored via this meta-analysis.Ethics and dissemination:Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms.Osf Registration Number:DOI 10.17605/OSF.IO/Q8XA5.     

Association of transferrin G258A and transferrin receptor A82G polymorphisms with the risk of Parkinson disease in certain area

Background:It has been reported that polymorphisms of transferrin (TF) G258A and transferrin receptor (TFR) A82G might be associated with susceptibility to Parkinson disease (PD).Objective:Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association.Methods:By searching PubMed, Embase, Chinese National Knowledge Infrastructure, China Biological Medicine Database, and Wanfang Databases, the published articles about studies of the association of the TF G258A, TFR A82G gene polymorphisms with the risk of PD were collected. Q-statistics and I² statistics were calculated to examine heterogeneity and summary odds ratios (ORs) and 95% confidence intervals (95%CI) were evaluated the association.Results:Five studies assessed the relationship between TF G258A and risk of PD. A significant increased protective of A allele and AA genotype was observed in allele model and recessive model (the allele model A vs G: OR = 0.54, 95%CI 0.40–0.72, P < .001; the recessive model AA vs GA + GG: OR = 0.32, 95%CI 0.20–0.52, P < .001). The remaining models of the TF G258A genotype showed no significant association with PD risk, while the protective tendency were increased (the heterozygote model GA vs GG: OR = 0.93, 95%CI 0.61–1.43, P = .75; the homozygous model AA vs GG: OR = 0.47, 95%CI 0.21–1.04, P = .06; the dominant model GA + AA vs GG: OR = 0.75, 95%CI 0.50–1.11, P = .15). There was also a lack of association between TFR A82G polymorphism and PD (the allele model G vs A: OR = 0.92, 95%CI 0.75–1.13, P = .43; the heterozygote model AG vs AA: OR = 1.17, 95%CI 0.79–1.71, P = .43; the homozygous model GG vs AA: OR = 0.91, 95%CI 0.60–139, P = .66; the dominant model AG + GG vs AA: OR = 1.05, 95%CI 0.73–1.49, P = .81; the recessive model GG vs AG +AA: OR = 0.80, 95%CI 0.59–1.09, P = .16).Conclusion:Our study suggests that TF G258A polymorphism may be associated with PD, while TFR A82G polymorphism may not contribute to PD based on the current evidence.     

Association between MTHFR C677T and A1298C gene polymorphisms and maternal risk for Down syndrome: A protocol for systematic review and/or meta-analysis

Background:Down syndrome (DS) is one of the most common chromosomal abnormalities among live-born babies and one of the best-known intellectual disability disorders in humans. Errors leading to trisomy 21 are primarily arising from defects in chromosomal segregation during maternal meiosis (about 88% of cases), and the focus of many investigations has been to identify maternal risk factors favoring chromosome 21 malsegregation during oogenesis. Maternal polymorphisms of genes required for folate metabolism are the most investigated risk factors for the birth of children with DS. Through this review, we sought to investigate the association of the polymorphisms “C677T” and “A1298C” of the MTHFR gene with maternal risk for DS.Methods:We will use the databases PubMed, Embase, Scopus and Web of Science to search for case-control studies published from 1999 up to September 2021 without language restriction. Results will be presented as relative risks and 95% confidence intervals for dichotomous outcomes and mean differences, or standardized mean differences along with 95% confidence intervals, for continuous outcomes. The all data synthesis will be analyzed on the Review Manager 5.2 version software.Results:This study will be able to clarify all the doubts we seek and that it will be able to provide accurate data that will be able to describe how these polymorphisms can act to increase the predisposition for the birth of children with DS in different populations and under different dietary conditions.Conclusions:This study will clarify the relationship between C677T and A1298C polymorphisms MTHFR gene with increased the maternal risk for Down syndrome.Registration:This systematic review and meta-analysis protocol has been registered on the Prospective Registry of International Systematic Review and Meta-analyses: CRD42021269338.     

Efficacy of combined angiotensin II receptor blocker with tripterygium glycosides on diabetic nephropathy: A protocol for meta-analysis

Background:Several studies have reported good results for angiotensin II receptor blockers (ARB) combined with tripterygium glycosides (TGs) in the treatment of diabetic nephropathy (DN). However, because a small number of cases were included in each study, the statistical power was limited. Therefore, we performed a protocol for meta-analysis to further evaluate the clinical efficacy and safety of combined ARB and TGs in treatment of DN.Methods:The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, Science Direct up to April 2021. Outcome measures were 24-h urinary total protein, urinary albumin excretion rate, serum creatinine, blood urea nitrogen, albumin, hemoglobin A1c, β2-microglobulin and serum glutamic pyruvic transaminase. The risk of bias assessment of the included studies was performed by two authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). We performed meta-analysis using STATA 11.0.Results:The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.Conclusion:The findings will provide helpful evidence for the application of combined ARB and TGs in the treatment of DN.OSF registration number:10.17605/OSF.IO/ARGE3     

Noradrenergic genes polymorphisms and response to methylphenidate in children with ADHD: A systematic review and meta-analysis

Background:Attention-deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, and methylphenidate (MPH) is considered one of the first-line medicine for ADHD. Unfortunately, this medication is only effective for some children with ADHD. This meta-analysis was conducted to evaluate whether noradrenergic gene polymorphisms impact the efficacy of MPH in children with ADHD.Methods:Candidate gene studies published in English until March 1, 2020, were identified through literature searches on PubMed, Web of Science, and Embase. Data were pooled from individual clinical trials considering MPH pharmacogenomics. According to the heterogeneity, the odds ratio and mean differences were calculated by applying fixed-effects or random-effects models.Results:This meta-analysis includes 15 studies and 1382 patients. Four polymorphisms of the NET gene (rs5569, rs28386840, rs2242446, rs3785143) and 2 polymorphisms of the α2A-adrenergic receptor gene (ADRA2A) gene (MspI and DraI) were selected for the analysis. In the pooled data from all studies, T allele carriers of the rs28386840 polymorphism were significantly more likely to respond to MPH (P < .001, OR_Tcarriers = 2.051, 95% confidence interval [CI]:1.316, 3.197) and showed a relationship with significantly greater hyperactive-impulsive symptoms improvement (P < .001, mean difference:1.70, 95% CI:0.24, 3.16). None of the ADRA2A polymorphisms correlated significantly with MPH response as a whole. However, G allele carriers of the MspI polymorphism showed a relationship with significantly inattention symptoms improvement (P < .001, mean difference:0.31, 95% CI: 0.15, 0.47).Conclusion:Our meta-analysis results indicate that the noradrenergic gene polymorphisms may impact MPH response. The NET rs28386840 is linked to improved MPH response in ADHD children. And the ADRA2A MspI is associated with inattention symptom improvements. Further investigations with larger samples will be needed to confirm these results.Registration: PROSPERO (no. CRD42021265830).