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Arquivos de Gastroenterologia May 2019There is increasing evidence to show that TNF-α -308G>A polymorphism may be a risk factor for celiac disease, but the results are inconsistent. (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is increasing evidence to show that TNF-α -308G>A polymorphism may be a risk factor for celiac disease, but the results are inconsistent.
OBJECTIVE
Thus, we aimed to perform a meta-analysis involving published studies up to January 2019 to elucidate the association.
METHODS
To assess the effect of TNF-α -308G>A polymorphism on celiac disease susceptibility, we searched PubMed, ISI Web of Knowledge, Chinese National Knowledge Infrastructure (CNKI) databases to identify eligible studies, without restriction. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to celiac disease.
RESULTS
A total of 11 studies with 1147 cases and 1774 controls were selected for this meta-analysis. The pooled results indicated that TNF-α -308G>A polymorphism was associated with increased risk of celiac disease (A vs G: OR=2.077, 95% CI=1.468-2.939, P=≤0.001; AA vs GG: OR=8.512, 95% CI=3.740-19.373, P=≤0.001; AA+AG vs GG: OR=1.869, 95% CI=1.161-3.008, P=0.010; and AA+AG vs GG: OR=4.773, 95% CI=3.181-7.162, P≤0.001). Subgroup analysis by ethnicity also revealed significant association in Caucasians. In addition, there was a significant association between TNF-α -308G>A polymorphism and celiac disease risk in Italy, Spain and PCR-FRLP group studies.
CONCLUSION
Our meta-analysis suggests that the TNF-α -308G>A polymorphism plays an important role in celiac disease susceptibility. However, our results are still needed to strengthen by further studies in different ethnicities and larger sample sizes.
Topics: Celiac Disease; Genetic Predisposition to Disease; Humans; Polymorphism, Single Nucleotide; Risk Factors; Tumor Necrosis Factor-alpha
PubMed: 31141070
DOI: 10.1590/S0004-2803.201900000-20 -
BMC Medical Genetics Feb 2020The goal of this study was to review relevant case-control studies to determine the association of tumor necrosis factor-α (TNF-α) gene polymorphisms and coronary... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The goal of this study was to review relevant case-control studies to determine the association of tumor necrosis factor-α (TNF-α) gene polymorphisms and coronary artery disease (CAD) susceptibility.
METHODS
Using appropriate keywords, we identified relevant studies using PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP. Key pertinent sources in the literature were also reviewed, and all articles published through April 2019 were considered for inclusion. Based on eligible studies, we performed a meta-analysis of association between 308G/A, 238G/A, 857C/T, 863C/A and 1031 T/C polymorphisms in TNF-α and risk of CAD.
RESULTS
We found 25 studies that were consistent with this meta-analysis, including 7697 patients in the CAD group and 9655 control patients. TNF-α 308G/A locus A showed no significant association with CAD susceptibility by the five models in the analysis of the overall population, European, African, South Asian, and North Asian patients. TNF-α 863C/A locus A and 1031 T/C locus C exhibited no significant association with CAD susceptibility. TNF-α 238G/A locus A had no significant association with CAD susceptibility in the overall population. However, TNF-α 238G/A locus A showed significant association with higher CAD susceptibility in the subgroup of Europeans and north Asians. TNF-α 857C/T locus T had no significant association with CAD susceptibility in the analysis of the overall population and Europeans. In the north Asian population, TNF-α 857C/T locus T was associated with lower CAD susceptibility by the heterozygote model.
CONCLUSION
TNF-α 308G/A, 857C/T, 863C/A, and 1031 T/C has no significant association with CAD susceptibility. TNF-α 238G/A locus A has significant association with CAD susceptibility in Europeans and north Asians, but has no significant association in the overall population. Studies with a larger sample size are required to confirm the association between TNF-α 238G/A and CAD susceptibility.
Topics: Coronary Artery Disease; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Tumor Necrosis Factor-alpha
PubMed: 32046680
DOI: 10.1186/s12881-020-0952-2 -
Alimentary Pharmacology & Therapeutics Dec 2011The use of proton pump inhibitors (PPIs) is increasing worldwide. Suppression of gastric acid alters the susceptibility to enteric bacterial pathogens. AIM This... (Review)
Review
The use of proton pump inhibitors (PPIs) is increasing worldwide. Suppression of gastric acid alters the susceptibility to enteric bacterial pathogens. AIM This systematic review was undertaken to examine the relationship between PPI use and susceptibility to enteric infections by a specific pathogen based on published literature and to discuss the potential mechanisms of PPI enhanced pathogenesis of enteric infections. METHODS PubMed, OVID Medline Databases were searched. Search terms included proton pump inhibitors and mechanisms of, actions of, gastric acid, enteric infections, diarrhoea, Clostridium difficile, Salmonella, Shigella and Campylobacter. RESULTS The use of PPIs increases gastric pH, encourages growth of the gut microflora, increases bacterial translocation and alters various immunomodulatory and anti-inflammatory effects. Enteric pathogens show variable gastric acid pH susceptibility and acid tolerance levels. By multiple mechanisms, PPIs appear to increase susceptibility to the following bacterial enteropathogens: Salmonella, Campylobacter jejuni, invasive strains of Escherichia coli, vegetative cells of Clostridium difficile, Vibrio cholerae and Listeria. We describe the available evidence for enhanced susceptibility to enteric infection caused by Salmonella, Campylobacter and C. difficile by PPI use, with adjusted relative risk ranges of 4.2-8.3 (two studies); 3.5-11.7 (four studies); and 1.2-5.0 (17 of 27 studies) for the three respective organisms. CONCLUSIONS Severe hypochlorhydria generated by PPI use leads to bacterial colonisation and increased susceptibility to enteric bacterial infection. The clinical implication of chronic PPI use among hospitalized patients placed on antibiotics and travellers departing for areas with high incidence of diarrhoea should be considered by their physicians.
Topics: Anti-Ulcer Agents; Bacterial Infections; Disease Susceptibility; Gastric Acid; Gastrointestinal Diseases; Humans; Hydrogen-Ion Concentration; Proton Pump Inhibitors; Risk Factors; Time Factors
PubMed: 21999643
DOI: 10.1111/j.1365-2036.2011.04874.x -
Fetal and Pediatric Pathology Apr 2021This meta-analysis was carried out to evaluate the associations between IL-10 polymorphisms and Kawasaki disease (KD) risk. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis was carried out to evaluate the associations between IL-10 polymorphisms and Kawasaki disease (KD) risk.
METHODS
A comprehensive literature search was performed using PubMed, EMBASE, China National Knowledge Infrastructure and SciELO for all relevant studies evaluating IL-10 polymorphism and susceptibility to KD. The associations were measured by odds ratios (ORs) and its corresponding 95% confidence intervals (CIs).
RESULTS
A total of 13 studies including four studies on -1082 A > G, four studies on -819 T > C and five studies on -592 A > C polymorphism were selected. Pooled data revealed that IL-10 -592 A > C polymorphism was significantly associated with an increased risk of KD (C vs. A: OR = 0.402, 95% CI 0.194-0.832, = 0.014). However, IL-10 -1082 A > G and -819 T > C polymorphisms were not significantly associated with risk of KD under all five genetic models.
CONCLUSIONS
Our results revealed that IL-10 -592 A > C polymorphism was associated with risk of KD, while IL-10 -1082 A > G and -819 T > C polymorphisms were not involved in the development of KD.
Topics: China; Genetic Predisposition to Disease; Humans; Interleukin-10; Mucocutaneous Lymph Node Syndrome; Polymorphism, Single Nucleotide
PubMed: 31738634
DOI: 10.1080/15513815.2019.1686789 -
Medicine Jul 2018BCL-2 Associated X (BAX) is an important modulator of apoptosis. The associations between BAX gene polymorphism and cancer susceptibility and prognosis in different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
BCL-2 Associated X (BAX) is an important modulator of apoptosis. The associations between BAX gene polymorphism and cancer susceptibility and prognosis in different ethnic groups and types of cancer have yielded controversial results. To reconcile the results, a systematic review followed by meta-analysis was performed to assess the associations.
METHODS
A systematic search of Medline database (PubMed), EMBASE, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang databases for publications on BAX polymorphisms, and susceptibility and prognosis was carried out until July 2017. Retrieved 14 articles met the inclusions. Summary odds ratios (ORs) and hazard ratios (HRs) with their 95% confidence intervals (CIs) were harnessed to determine the strength of correlation between BAX polymorphisms and cancer susceptibility and prognosis, which were combined using fixed- or random-effects models as appropriate.
RESULTS
A total of 12 trials involving 3321 cases and 3209 controls were included in our pooled analysis regarding the polymorphisms and the susceptibility of cancers. Overall, results of the present meta-analysis demonstrated that there was no significant association between BAX polymorphisms and susceptibility of cancers (OR = 1.052, 95% CI: 0.827-1.339, P = .679, A vs G). Even in a stratified analysis by ethnicity and the sources of control groups, the results were consistent. Four retrospective studies of 549 cases qualified for meta-analysis were identified to set forth the associations of the polymorphisms with cancer prognosis. Our results suggested that BAX gene polymorphisms were significantly associated with unfavorable prognosis (HR = 1.735, 95% CI: 1.368-2.202, P = .000, GG vs GA/AA).
CONCLUSION
There is no significant association between BAX gene polymorphism and cancer susceptibility, but it probably contributes to increased adverse prognosis to cancer.
Topics: Genetic Predisposition to Disease; Humans; Neoplasms; Polymorphism, Genetic; Prognosis; bcl-2-Associated X Protein
PubMed: 30024563
DOI: 10.1097/MD.0000000000011591 -
Cell Biochemistry and Biophysics Sep 2014Accumulating studies have evaluated the association of Alpha-2-Macroglobulin gene (A2M) 5 bp insertion/deletion (5 bp I/D, rs3832852) and Ile1000Val (rs669)... (Meta-Analysis)
Meta-Analysis Review
Influence of Alpha-2-Macroglobulin 5 bp I/D and Ile1000Val polymorphisms on the susceptibility of Alzheimer's disease: a systematic review and meta-analysis of 52 studies.
Accumulating studies have evaluated the association of Alpha-2-Macroglobulin gene (A2M) 5 bp insertion/deletion (5 bp I/D, rs3832852) and Ile1000Val (rs669) polymorphisms with Alzheimer's disease (AD) risk, but the results remain inconclusive. To investigate whether these two polymorphisms facilitate the susceptibility to AD, we conducted a comprehensive systematic review and meta-analysis. Databases of PubMed, Embase, Web of Science, Medline, CNKI, and Google Scholar were searched to get the genetic association studies. All statistical analyses were conducted with Review Manager 5.2 and STATA11.0. Fifty-two articles were included in the final meta-analysis. We performed meta-analysis of 39 studies involving 8,267 cases and 7,932 controls for the 5 bp I/D polymorphism and 27 studies involving 6,585 cases and 6,637 controls for the Ile/Val polymorphism. Overall results did not show significant association between these two polymorphisms and AD risk in dominant, recessive, and multiplicative genetic models. On the stratification analyses by ethnicity and APOE ε4 status with genotypes of polymorphism sites, similar negative associations were found. The meta-analysis suggests that there is no enough evidence for associations of A2M gene polymorphisms (5 bp I/D, Ile1000Val) with AD risk at present, even after stratification by ethnicity and APOE ε4 with genotypes of polymorphism sites. However, due to the heterogeneity in the meta-analysis, the results should be interpreted with caution.
Topics: Alzheimer Disease; Genetic Predisposition to Disease; Humans; INDEL Mutation; Polymorphism, Single Nucleotide; alpha-Macroglobulins
PubMed: 24756728
DOI: 10.1007/s12013-014-9950-3 -
Clinical Reviews in Allergy & Immunology Dec 2020Activated phosphoinositide 3-kinase delta syndrome (APDS) is a novel primary immunodeficiency (PID) caused by heterozygous gain of function mutations in PI3Kδ catalytic... (Meta-Analysis)
Meta-Analysis
Activated phosphoinositide 3-kinase delta syndrome (APDS) is a novel primary immunodeficiency (PID) caused by heterozygous gain of function mutations in PI3Kδ catalytic p110δ (PIK3CD) or regulatory p85α (PIK3R1) subunits leading to APDS1 and APDS2, respectively. Patients with APDS present a spectrum of clinical manifestations, particularly recurrent respiratory infections and lymphoproliferation. We searched PubMed, Web of Science, and Scopus databases for APDS patients and screened for eligibility criteria. A total of 243 APDS patients were identified from 55 articles. For all patients, demographic, clinical, immunologic, and molecular data were collected. Overall, 179 APDS1 and 64 APDS2 patients were identified. The most common clinical manifestations were respiratory tract infections (pneumonia (43.6%), otitis media (28.8%), and sinusitis (25.9%)), lymphoproliferation (70.4%), autoimmunity (28%), enteropathy (26.7%), failure to thrive (20.6%), and malignancy (12.8%). The predominant immunologic phenotype was hyper-IgM syndrome (48.1%). Immunologic profiling showed decreased B cells in 74.8% and CD4 T cells in 64.8% of APDS patients. The c.3061 G>A (p. E1021K) mutation in APDS1 with 85% frequency and c.1425+1 G> (A, C, T) (p.434-475del) mutation in APDS2 with 79% frequency were hotspot mutations. The majority of APDS patients were placed on long-term immunoglobulin replacement therapy. Immunosuppressive agents such as rituximab, tacrolimus, rapamycin, and leniolisib were also administered for autoimmunity and inflammatory complications. In addition, hematopoietic stem cell transplantation (HSCT) was used in 12.8% of patients. APDS has heterogynous clinical manifestations. It should be suspected in patients with history of recurrent respiratory infections, lymphoproliferation, and raised IgM levels. Moreover, HSCT should be considered in patients with severe and complicated clinical manifestations with no or insufficient response to the conventional therapies.
Topics: Adolescent; Adult; Autoimmunity; Biomarkers; Child; Class I Phosphatidylinositol 3-Kinases; Disease Susceptibility; Female; Gain of Function Mutation; Genetic Predisposition to Disease; Humans; Male; Phenotype; Primary Immunodeficiency Diseases; Young Adult
PubMed: 31111319
DOI: 10.1007/s12016-019-08738-9 -
Gene Aug 2022COVID-19 is associated with several risk factors such as distinct ethnicities (genetic ancestry), races, sexes, age, pre-existing comorbidities, smoking, and genetics.... (Review)
Review
BACKGROUND
COVID-19 is associated with several risk factors such as distinct ethnicities (genetic ancestry), races, sexes, age, pre-existing comorbidities, smoking, and genetics. The authors aim to evaluate the correlation between variability in the host genetics and the severity and susceptibility towards COVID-19 in this study.
METHODS
Following the PRISMA guidelines, we retrieved all the relevant articles published until September 15, 2021, from two online databases: PubMed and Scopus.
FINDINGS
High-risk HLA haplotypes, higher expression of ACE polymorphisms, and several genes of cellular proteases such as TMPRSS2, FURIN, TLL-1 increase the risk of susceptibility and severity of COVID-19. In addition, upregulation of several genes encoding for both innate and acquired immune systems proteins, mainly CCR5, IFNs, TLR, DPPs, and TNF, positively correlate with COVID-19 severity. However, reduced expression or polymorphisms in genes affecting TLR and IFNλ increase COVID-19 severity.
CONCLUSION
Higher expression, polymorphisms, mutations, and deletions of several genes are linked with the susceptibility, severity, and clinical outcomes of COVID-19. Early treatment and vaccination of individuals with genetic predisposition could help minimize the severity and mortality associated with COVID-19.
Topics: COVID-19; Genetic Predisposition to Disease; Haplotypes; Humans; Polymorphism, Genetic; SARS-CoV-2
PubMed: 35714803
DOI: 10.1016/j.gene.2022.146674 -
Clinical Epigenetics Apr 2019Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual differences in their susceptibility to disease and death. Epigenetic mechanisms may play a role in human ageing, and DNA methylation age biomarkers may be good predictors of age-related diseases and mortality risk. The aims of this systematic review were to identify and synthesise the evidence for an association between peripherally measured DNA methylation age and longevity, age-related disease, and mortality risk.
METHODS
A systematic search was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using relevant search terms, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsychINFO databases were searched to identify articles meeting the inclusion criteria. Studies were assessed for bias using Joanna Briggs Institute critical appraisal checklists. Data was extracted from studies measuring age acceleration as a predictor of age-related diseases, mortality or longevity, and the findings for similar outcomes compared. Using Review Manager 5.3 software, two meta-analyses (one per epigenetic clock) were conducted on studies measuring all-cause mortality.
RESULTS
Twenty-three relevant articles were identified, including a total of 41,607 participants. Four studies focused on ageing and longevity, 11 on age-related disease (cancer, cardiovascular disease, and dementia), and 11 on mortality. There was some, although inconsistent, evidence for an association between increased DNA methylation age and risk of disease. Meta-analyses indicated that each 5-year increase in DNA methylation age was associated an 8 to 15% increased risk of mortality.
CONCLUSION
Due to the small number of studies and heterogeneity in study design and outcomes, the association between DNA methylation age and age-related disease and longevity is inconclusive. Increased epigenetic age was associated with mortality risk, but positive publication bias needs to be considered. Further research is needed to determine the extent to which DNA methylation age can be used as a clinical biomarker.
Topics: Aging; DNA Methylation; Epigenesis, Genetic; Genetic Association Studies; Genetic Markers; Genetic Predisposition to Disease; Humans; Mortality
PubMed: 30975202
DOI: 10.1186/s13148-019-0656-7 -
Journal of Nutrigenetics and... 2017ApaI, FokI, TaqI, and BsmI polymorphisms in the vitamin D receptor (VDR) gene have been reported to be associated with the risk of coronary artery disease (CAD),... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
ApaI, FokI, TaqI, and BsmI polymorphisms in the vitamin D receptor (VDR) gene have been reported to be associated with the risk of coronary artery disease (CAD), although the results of previous studies have been inconsistent. The aim of this study was to explore whether these polymorphisms play a role in the genetic susceptibility to CAD.
METHODS
A comprehensive search of Medline and Embase databases was conducted for studies evaluating the association between the VDR polymorphisms and CAD risk. Odds ratios with 95% confidence intervals were calculated to assess the strength of association in the dominant model, recessive model, allelic model, and genotypes contrast.
RESULTS
Nine studies involving a total of 5,259 cases and 1,981 controls were finally included in this meta-analysis. Overall, no significant associations were found between ApaI, FokI, TaqI, and BsmI polymorphisms and the risk of CAD in any of the genetic models (all p ˃ 0.05). Moreover, a subgroup analysis by ethnicity did not reveal a significant relationship between any of the examined polymorphisms and CAD risk in Caucasians and East-Asians for any model (all p ˃ 0.05).
CONCLUSION
Current evidence suggests that the ApaI, FokI, TaqI, and BsmI polymorphisms of the VDR gene might not be associated with genetic susceptibility to CAD. Further well-designed studies with large sample sizes are needed to confirm our results.
Topics: Coronary Artery Disease; Female; Genetic Predisposition to Disease; Humans; Male; Molecular Epidemiology; Nutrigenomics; Polymorphism, Restriction Fragment Length; Receptors, Calcitriol; Risk Factors
PubMed: 28351026
DOI: 10.1159/000455914