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Gene Nov 2022The COVID-19 pandemic has spawned global health crisis of unprecedented magnitude, claiming millions of lives and pushing healthcare systems in many countries to the... (Meta-Analysis)
Meta-Analysis Review
The COVID-19 pandemic has spawned global health crisis of unprecedented magnitude, claiming millions of lives and pushing healthcare systems in many countries to the brink. Among several factors that contribute to an increased risk of COVID-19 and progression to exacerbated manifestations, host genetic landscape is increasingly being recognized as a critical determinant of susceptibility/resistance to infection and a prognosticator of clinical outcomes in infected individuals. Recently, several case-control association studies investigated the influence of human gene variants on COVID-19 susceptibility and severity to identify the culpable mutations. However, a comprehensive synthesis of the recent advances in COVID-19 host genetics research was lacking, and the inconsistent findings of the association studies required reliable evaluation of the strength of association with greater statistical power. In this study, we embarked on a systematic search of all possible reports of genetic association with COVID-19 till April 07, 2022, and performed meta-analyses of all the genetic polymorphisms that were examined in at least three studies. After identifying a total of 84 studies that investigated the association of 130 polymorphisms in 61 genes, we performed meta-analyses of all the eligible studies. Seven genetic polymorphisms involving 15,550 cases and 444,007 controls were explored for association with COVID-19 susceptibility, of which, ACE1 I/D rs4646994/rs1799752, APOE rs429358, CCR5 rs333, and IFITM3 rs12252 showed increased risk of infection. Meta-analyses of 11 gene variants involving 6702 patients with severe COVID-19 and 8640 infected individuals with non-severe manifestations revealed statistically significant association of ACE2 rs2285666, ACE2 rs2106809, ACE2 rs2074192, AGTR1 rs5186, and TNFA rs1800629 with COVID-19 severity. Overall, our study presents a synthesis of evidence on all the genetic determinants implicated in COVID-19 to date, and provides evidence of correlation between the above polymorphisms with COVID-19 susceptibility and severity.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Genetic Predisposition to Disease; Human Genetics; Humans; Membrane Proteins; Pandemics; RNA-Binding Proteins; SARS-CoV-2
PubMed: 35987511
DOI: 10.1016/j.gene.2022.146790 -
Medicina (Kaunas, Lithuania) Jul 2022: Starting in early December 2019, the novel Coronavirus Disease (COVID-19) from infection with COVID-19 has caused a global pandemic. Many aspects of its pathogenesis... (Review)
Review
: Starting in early December 2019, the novel Coronavirus Disease (COVID-19) from infection with COVID-19 has caused a global pandemic. Many aspects of its pathogenesis and related clinical consequences are still unclear. Early diagnosis and dynamic monitoring of prognostic factors are essential to improve the ability to manage COVID-19 infection. This study aimed to provide an account of the role played by vitamins C and D on the onset, progression and severity of COVID-19. Clinical features and infection-related risk factors are also briefly discussed. : In March 2022, the main online databases were accessed. All the articles that investigate the possible role of vitamins C and D on COVID-19 susceptibility, severity and progression were considered. : The current evidence on vitamin C and D supplementation in patients with COVID-19 infection is inconsistent and controversial. In some studies, vitamins were used as coadjuvant of a formal experimental therapy, while in others as main treatment. Ethnicity and hospital setting (inpatient/outpatient) were also variable. Moreover, there was no consensus between studies in administration protocol: high heterogeneity in dosage, administration, and duration of the treatment were evident. Finally, some studies administered vitamins pre- and/or during COVID infection, in patients with different risk factors and infection severity. : While waiting to develop a targeted, safe and effective therapy, it is important to investigate individual predisposition and proper disease management. Concluding, available data on the use of nutraceuticals in COVID-19 are inconsistent. However, there is a lack of evidence-based guidelines which recommend vitamin C and D supplementation in patients with COVID-19, and results from high quality randomised controlled trials (RCTs) are inconsistent. Current investigations so far are mostly observational, and include a relatively small sample size which can lead to biased results. Large-scale multicentre studies are therefore needed.
Topics: Ascorbic Acid; COVID-19; Disease Susceptibility; Humans; Pandemics; SARS-CoV-2; Vitamin D; Vitamins
PubMed: 35888660
DOI: 10.3390/medicina58070941 -
Rheumatology (Oxford, England) Sep 2014Vitamin D appears to have significant effects on both innate and acquired immunity and deficiency may be associated with both susceptibility and disease severity in some... (Review)
Review
OBJECTIVES
Vitamin D appears to have significant effects on both innate and acquired immunity and deficiency may be associated with both susceptibility and disease severity in some autoimmune conditions. There has been little focus on the potential immunomodulatory role of vitamin D in AS. This study systematically reviews the evidence for an association between vitamin D deficiency and disease susceptibility and severity in AS.
METHODS
A systematic review was conducted using Medline, EMBASE, Web of Science and conference abstracts of the European League Against Rheumatism (2002-13), British Society for Rheumatology (1993-2013) and ACR (2006-13).
RESULTS
Fifteen original articles and five conference abstracts met the criteria for inclusion. All were cross-sectional in design. Seven of 11 studies identified lower concentrations of 25-hydroxyvitamin D (25OHD) in AS patients compared with healthy controls. A significant inverse correlation between 25OHD and disease activity was observed in 5 of 11 studies. The majority of studies that failed to demonstrate significant findings used inappropriate statistical methods.
CONCLUSION
Cross-sectional studies using appropriate statistical analyses have highlighted that AS is associated with lower vitamin D concentrations. Within groups of AS patients there is some evidence that low vitamin D concentrations are associated with higher disease activity. However, there are insufficient published data to support an immunomodulatory role for vitamin D in AS. Further study with a longitudinal design is required to understand whether optimizing vitamin D in AS has potential as a disease-modifying intervention.
Topics: Cross-Sectional Studies; Disease Susceptibility; Humans; Spondylitis, Ankylosing; Vitamin D; Vitamin D Deficiency
PubMed: 24706990
DOI: 10.1093/rheumatology/keu042 -
Frontiers in Immunology 2022Kawasaki disease (KD) is an acute autoimmune vascular disease featured with a long stage of febrile. It predominantly afflicts children under 5 years old and causes an... (Review)
Review
Kawasaki disease (KD) is an acute autoimmune vascular disease featured with a long stage of febrile. It predominantly afflicts children under 5 years old and causes an increased risk of cardiovascular combinations. The onset and progression of KD are impacted by many aspects, including genetic susceptibility, infection, and immunity. In recent years, many studies revealed that miRNAs, a novel class of small non-coding RNAs, may play an indispensable role in the development of KD differential expression and participation in the central pathogenesis of KD comprise of the modulation of immunity, inflammatory response and vascular dysregulation. Although specific diagnose criteria remains unclear up to date, accumulating clinical evidence indicated that miRNAs, as small molecules, could serve as potential diagnostic biomarkers and exhibit extraordinary specificity and sensitivity. Besides, miRNAs have gained attention in affecting therapies for Kawasaki disease and providing new insights into personalized treatment. Through consanguineous coordination with classical therapies, miRNAs could overcome the inevitable drug-resistance and poor prognosis problem in a novel point of view. In this review, we systematically reviewed the existing literature and summarized those findings to analyze the latest mechanism to explore the role of miRNAs in the treatment of KD from basic and clinical aspects retrospectively. Our discussion helps to better understand the pathogenesis of KD and may offer profound inspiration on KD diagnosis, treatment, and prognosis.
Topics: Child; Humans; Child, Preschool; Mucocutaneous Lymph Node Syndrome; MicroRNAs; Retrospective Studies; Genetic Predisposition to Disease
PubMed: 36353615
DOI: 10.3389/fimmu.2022.1016575 -
Cytokine Nov 2023Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease with high morbidity and mortality rates worldwide. Cytokines, which are the main... (Meta-Analysis)
Meta-Analysis Review
Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease with high morbidity and mortality rates worldwide. Cytokines, which are the main regulators of immune responses, play crucial roles in inflammatory diseases such as COPD. Moreover, certain genetic variations can alter cytokine expression, and changes in cytokine level or function can affect disease susceptibility. Therefore, investigating the association between genetic variations and disease progression can be useful for prevention and treatment. Several studies have explored the association between common genetic variations in cytokine genes and COPD susceptibility. In this study, we summarized the reported studies and, where possible, conducted a systematic review and meta-analysis to evaluate the genetic association between various cytokines and COPD pathogenesis. We extracted relevant articles from PubMed and Google Scholar databases using a standard systematic search strategy. We included a total of 183 studies from 78 separate articles that evaluated 50 polymorphisms in 12 cytokine genes in this study. Our analysis showed that among all reported cytokine polymorphisms (including TNF-α, TGF-β, IL1, IL1RN, IL4, IL4R, IL6, IL10, IL12, IL13, IL17, IL18, IL27, and IL33), only four variants, including TNF-α-rs1800629, TGF-β1-rs6957, IL13-rs1800925, and IL6-rs1800796, were associated with the risk of COPD development. This updated meta-analysis strongly supports the association of TNF-α-rs1800629, TGF-β1-rs6957, IL13-rs1800925, and IL6-rs1800796 variants with a high risk of COPD.
Topics: Humans; Polymorphism, Single Nucleotide; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Genetic Predisposition to Disease; Interleukin-13; Interleukin-6; Cytokines; Pulmonary Disease, Chronic Obstructive
PubMed: 37703677
DOI: 10.1016/j.cyto.2023.156352 -
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 -
Journal of Psychiatric Research Aug 2023Gene-environment interaction (G × E) refers to the change of genetic effects under the participation of environmental factors resulting in differences in genetic... (Review)
Review
BACKGROUND
Gene-environment interaction (G × E) refers to the change of genetic effects under the participation of environmental factors resulting in differences in genetic expression. G × E has been studied in the occurrence and development of many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD).
AIM
A systematic review was conducted to investigate the role of G × E plays in OCD. This review explored the relationship between G × E and the susceptibility to OCD occurrence, disease progression, and treatment response.
METHODS
This systematic literature search was performed using Web of Science, PubMed, Cochrane Library, and CNKI. Seven studies were selected, which included seven genes (BDNF, COMT, MAO, 5-HTT, SMAD4, PGRN, and SLC1A1) polymorphisms, polygenic risk score (PRS), and two environmental factors (childhood trauma and stressful life events).
RESULTS
Information from this systematic review indicated that G × E increased the susceptibility to OCD, played a crucial role in the clinical characteristics, and had an inconsistent impact on treatment response of OCD.
FUTURE DIRECTIONS
The multi-omics studies and the inclusion of G × E in future GWAS studies of OCD should be drawn more attention, which may contribute to a deeper understanding of the etiology of OCD as well as guide therapeutic interventions for the disease.
Topics: Humans; Gene-Environment Interaction; Genotype; Genetic Predisposition to Disease; Obsessive-Compulsive Disorder; Polymorphism, Genetic
PubMed: 37390623
DOI: 10.1016/j.jpsychires.2023.06.004 -
International Archives of Occupational... Jan 2023Pneumoconiosis, encompassing coal workers' pneumoconiosis (CWP), silicosis and asbestosis, is one of the most common occupational diseases in China. Previous studies... (Review)
Review
OBJECTIVE
Pneumoconiosis, encompassing coal workers' pneumoconiosis (CWP), silicosis and asbestosis, is one of the most common occupational diseases in China. Previous studies revealed significant associations between genetic variations and pneumoconiosis risk among individuals in different countries. With the known variability of genetic makeup between ethnicities, susceptibility to pneumoconiosis due to genetic differences is likely to be ethnicity-specific. The present review aimed at providing a comprehensive overview on the association between genetic polymorphisms and susceptibility of pneumoconiosis, specifically among people in China.
METHODS
The literature search was performed in seven English and Chinese databases using keywords related to the review aim. An appraisal of the methodological quality of the included studies was conducted using the assessment tool derived from the Strengthening the Reporting of Genetic Association Studies (STREGA) statement.
RESULTS
Forty-five studies were included in this review. Genotypes of specific genes which are associated with the risk of CWP, silicosis and asbestosis were reported. Our findings showed that genes encoding inflammatory cytokines have been examined extensively, and they demonstrated an association between these genes and pneumoconiosis risk. Gene-environment interactions in pneumoconiosis susceptibility were also reported by a number of studies.
CONCLUSIONS
This review summarised the evidence demonstrating the association between genetic polymorphisms and pneumoconiosis susceptibility among people in China, and that various genotypes could modify their risk to develop pneumoconiosis. The findings prompt that identification of individuals at high pneumoconiosis risk through genetic screening and strategies limiting their exposure to dust could be a potential strategy for the control of this occupational disease in China.
Topics: Humans; Asbestosis; Genetic Predisposition to Disease; Coal Mining; Pneumoconiosis; Silicosis; Anthracosis; Occupational Diseases; China
PubMed: 35906431
DOI: 10.1007/s00420-022-01893-1 -
BMC Medical Genomics Sep 2019Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic variants associated with susceptibility, phenotype and outcome of community acquired pneumococcal pneumonia (CAP) and invasive pneumococcal disease (IPD).
METHODS
We searched PubMed for studies on the influence of host genetics on susceptibility, phenotype, and outcome of CAP and IPD between Jan 1, 1983 and Jul 4, 2018. We listed methodological characteristics and when genetic data was available we calculated effect sizes. We used fixed or random effect models to calculate pooled effect sizes in the meta-analysis.
RESULTS
We identified 1219 studies of which 60 studies involving 15,358 patients were included. Twenty-five studies (42%) focused on susceptibility, 8 (13%) on outcome, 1 (2%) on disease phenotype, and 26 (43%) on multiple categories. We identified five studies with a hypothesis free approach of which one resulted in one genome wide significant association in a gene coding for lincRNA with pneumococcal disease susceptibility. We performed 17 meta-analyses of which two susceptibility polymorphisms had a significant overall effect size: variant alleles of MBL2 (odds ratio [OR] 1·67, 95% confidence interval [CI] 1·04-2·69) and a variant in CD14 (OR 1·77, 95% CI 1·18-2·66) and none of the outcome polymorphisms.
CONCLUSIONS
Studies have identified several host genetics factors influencing risk of pneumococcal disease, but many result in non-reproducible findings due to methodological limitations. Uniform case definitions and pooling of data is necessary to obtain more robust findings.
Topics: Disease Susceptibility; Humans; Lipopolysaccharide Receptors; Mannose-Binding Lectin; Odds Ratio; Phenotype; Pneumococcal Infections; Polymorphism, Genetic; RNA, Long Noncoding; Risk Factors
PubMed: 31519222
DOI: 10.1186/s12920-019-0572-x -
Neurological Sciences : Official... Feb 2018Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in multiple sclerosis (MS). However, published studies demonstrated differences concerning... (Meta-Analysis)
Meta-Analysis Review
Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in multiple sclerosis (MS). However, published studies demonstrated differences concerning design and effect size. A meta-analysis is necessary to determine the magnitude of the association between VDR polymorphisms and MS risk. The aim of the current study was to quantify the magnitude of the association between BsmI, FokI, ApaI, and TaqI VDR polymorphisms and MS risk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search and meta-analysis of the VDR gene polymorphisms and the risk of MS. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated by using Stata Version 11.0 with dominant and recessive models and allele analyses. A total of 4013 cases and 4218 controls in 24 case-control studies were included in the meta-analyses. The results did not indicate an association between any of the VDR polymorphisms and the risk of MS among overall populations, Asians, and Caucasians. However, our subgroup analysis suggests that the A allele was associated with MS risk in Asian populations (P = 0.005, OR = 1.267, 95% CI 1.074-1.496). Interestingly, the sensitivity analysis excluding studies with controls not in HWE showed insignificant association between the A allele and MS risk (P = 0.211), which was different from those in the non-sensitivity analysis. Our preliminary results indicate the VDR gene ApaI, BsmI, FokI, and TaqI polymorphisms may not be associated with elevated MS risk among overall populations. But ApaI polymorphism may confer different susceptibility to MS among different populations, and more well-designed studies with a large sample size are still needed to validate our results.
Topics: Asian People; Case-Control Studies; Genetic Predisposition to Disease; Humans; Multiple Sclerosis; Polymorphism, Genetic; Receptors, Calcitriol
PubMed: 29110148
DOI: 10.1007/s10072-017-3175-3