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PloS One 2022Although advanced age and presence of comorbidities significantly impact the variation observed in the clinical symptoms of COVID-19, it has been suggested that genetic... (Meta-Analysis)
Meta-Analysis
Although advanced age and presence of comorbidities significantly impact the variation observed in the clinical symptoms of COVID-19, it has been suggested that genetic variants may also be involved in the disease. Thus, the aim of this study was to perform a systematic review with meta-analysis of the literature to identify genetic polymorphisms that are likely to contribute to COVID-19 pathogenesis. Pubmed, Embase and GWAS Catalog repositories were systematically searched to retrieve articles that investigated associations between polymorphisms and COVID-19. For polymorphisms analyzed in 3 or more studies, pooled OR with 95% CI were calculated using random or fixed effect models in the Stata Software. Sixty-four eligible articles were included in this review. In total, 8 polymorphisms in 7 candidate genes and 74 alleles of the HLA loci were analyzed in 3 or more studies. The HLA-A*30 and CCR5 rs333Del alleles were associated with protection against COVID-19 infection, while the APOE rs429358C allele was associated with risk for this disease. Regarding COVID-19 severity, the HLA-A*33, ACE1 Ins, and TMPRSS2 rs12329760T alleles were associated with protection against severe forms, while the HLA-B*38, HLA-C*6, and ApoE rs429358C alleles were associated with risk for severe forms of COVID-19. In conclusion, polymorphisms in the ApoE, ACE1, TMPRSS2, CCR5, and HLA loci appear to be involved in the susceptibility to and/or severity of COVID-19.
Topics: Apolipoproteins E; COVID-19; Genetic Predisposition to Disease; HLA-A Antigens; Humans; Polymorphism, Genetic
PubMed: 35793369
DOI: 10.1371/journal.pone.0270627 -
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 -
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 -
Herz Dec 2022Current genetic association studies have reported conflicting results regarding the association between miRNA polymorphisms and myocardial infarction (MI) risk METHODS:... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Current genetic association studies have reported conflicting results regarding the association between miRNA polymorphisms and myocardial infarction (MI) risk METHODS: Relevant studies were retrieved from the PubMed, EMBASE, ISI Web of Science, and Scopus databases. Eligible studies determining the association between miRNA polymorphisms and MI susceptibility were included and a meta-analysis was performed to quantify the associations between miRNA polymorphisms and MI risk.
RESULTS
A total of eight studies with 2507 MI patients and 3796 healthy controls were included, dealing with nine miRNA genes containing 11 different loci, including miR-149 (rs71428439 and rs2292832), miR-126 (rs4636297 and rs1140713), miR-146a (rs2910164), miR-218 (rs11134527), miR-196a2 (rs11614913), miR-499 (rs3746444), miR-27a (rs895819), miR-26a‑1 (rs7372209), and miR-100 (rs1834306). miR-146a rs2910164 and miR-499 rs3746444 were determined to have a significant association with MI susceptibility, a finding that was supported by the meta-analysis (rs2910164: GG/CC, odds ratio [OR]: 1.40, 95% confidence interval [95% CI]: 1.05-1.74, p < 0.001; rs3746444: AA + AG/GG, OR = 2.04, 95% CI: 1.37-2.70, p < 0.001). Limited or conflicting data were found for the relationship between the other miRNA polymorphisms (rs71428439, rs4636297, rs1140713, rs11134527, rs11614913, rs895819, rs7372209, rs1834306, rs2292832) and MI risk.
CONCLUSION
There was a significant association between rs2910164 and rs3746444 and MI susceptibility. Further studies are required to investigate the role of miRNA polymorphisms in MI risk.
Topics: Humans; Genetic Association Studies; Genetic Predisposition to Disease; MicroRNAs; Myocardial Infarction; Polymorphism, Single Nucleotide
PubMed: 34878577
DOI: 10.1007/s00059-021-05086-3 -
Biochemical Genetics Oct 2021Several studies have previously assessed the association between interleukin (IL)-10 gene polymorphisms and the risk of asthma, leading to conflicting results. To... (Meta-Analysis)
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.
Topics: Asthma; Case-Control Studies; Genetic Predisposition to Disease; Humans; Interleukin-10; Polymorphism, Single Nucleotide; Promoter Regions, Genetic
PubMed: 33755871
DOI: 10.1007/s10528-021-10056-9 -
Cytokine Jan 2022Inflammatory bowel disease (IBD) is a chronic inflammatory disease that affects the small intestine, colon, and rectum. We evaluated associations between the interleukin... (Meta-Analysis)
Meta-Analysis
Inflammatory bowel disease (IBD) is a chronic inflammatory disease that affects the small intestine, colon, and rectum. We evaluated associations between the interleukin 10 (IL-10) rs3024505 polymorphism and IBD, ulcerative colitis (UC), and Crohn's disease (CD) by meta-analysis. All peer-reviewed manuscripts concerning the relationship between IL-10_rs3024505 and IBD identified by searing the PubMed, Cochrane Library, EMBASE, and Chinese Medical Database were examined. The association between IL-10_rs3024505 and IBD was evaluated in allele (AG), recessive (RG), dominant (DG), homozygous (HMG), and heterozygous (HTG) genetic models. Associations were also conducted on IBD subtypes, CD and UC, and ethnicity (Non-Europeans and Europeans) subgroups. The meta-analysis included 13 studies, 8552 cases (IBD patients), and 12,830 healthy controls. Subgroup analysis of IBD (UC and CD) revealed heterogeneity in AG, DG, and HTG but no heterogeneity in RG or HMG. Moreover, AG, DG, and HTG did not show publication bias in IBD, CD, or UC, but RG and HMG exhibited publication bias. No heterogeneity and no publication bias were found among the five genetic models by a subgroup analysis of Non-Europeans and European ethnicities. The minor allele(T) of rs3024505 was significantly related to IBD: 1.37 (1.30-1.45) for AG, 2.06 (1.74-2.45) for RG, 1.39 (1.27-1.52) for DG, 2.25 (1.89-2.67) for HMG, and 1.32 (1.23-1.40) for HTG (all P < 0.00001). In the subgroup analysis of ethnicity, there was a significant effect of rs3024505 on IBD in Europeans but not non-Europeans: 1.38 (1.31-1.46) for AG, 2.07 (1.73-2.48) for RG, 1.39 (1.31-1.49) for DG, 2.26 (1.89-2.71) for HMG, and 1.33 (1.24-1.42) for HTG in Europeans (all P < 0.00001). Sensitivity analysis showed no dominant study in Europeans, but one study had a dominant impact in Non-Europeans. In conclusion, IL-10_rs3024505 polymorphism confers susceptibility to CD and UC in Europeans, but its impact should have conducted more studies in Non-Europeans.
Topics: Alleles; Animals; Genetic Predisposition to Disease; Humans; Inflammatory Bowel Diseases; Interleukin-10; Polymorphism, Single Nucleotide
PubMed: 34628128
DOI: 10.1016/j.cyto.2021.155721 -
Lung Cancer (Amsterdam, Netherlands) Sep 2014As the primary cause of lung cancer, whether smoking confers the same risk of lung cancer for women as men is unclear. Therefore, we aimed to compare male and female... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
As the primary cause of lung cancer, whether smoking confers the same risk of lung cancer for women as men is unclear. Therefore, we aimed to compare male and female susceptibility for cigarette smoking-attributable lung cancer.
METHODS
A systematic review and meta-analysis was conducted by searching articles published up to July 2013 in three online databases (MEDLINE, EMBASE, and Cochrane Database). All studies estimated the association of cigarette smoking with the risk of lung cancer between men and women, respectively. A random effects model with inverse variance weighting was used to pool data. Male to female ratio of relative risk (RRR) was calculated to compare male and female susceptibility for cigarette smoking-attributable lung cancer.
RESULTS
47 articles containing 404,874 individuals were included in the final analysis. Compared with non-smokers, male to female RRR was 1.61 (95%CI: 1.37, 1.89) among current smokers. Based on pathological type, adenocarcinoma had the highest RRR (1.42; 95%CI: 0.86, 2.35), followed by squamous cancer and small cell lung cancer. Furthermore, compared with non-smoking men, current smoking men had higher risk of lung cancer than women in spite of smoking quantity, smoking duration or years since quitting.
CONCLUSIONS
These findings indicated that males had higher susceptibility for cigarette smoking-attributable lung cancer than females. It is contradicted with traditional opinion that females would be more easily suffered from cigarette smoking-attributable health problems than males. Hence, tobacco control is very crucial in both males and females.
Topics: Disease Susceptibility; Female; Humans; Lung Neoplasms; Male; Odds Ratio; Sex Factors; Smoking
PubMed: 25064415
DOI: 10.1016/j.lungcan.2014.07.004 -
Human Immunology Oct 2018HLA-G is an immune checkpoint molecule. Since a differential molecule expression has been reported even for healthy individuals, many studies have focused on... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HLA-G is an immune checkpoint molecule. Since a differential molecule expression has been reported even for healthy individuals, many studies have focused on polymorphisms at HLA-G regulatory regions, particularly the 3' untranslated region (3'UTR). The presence/absence of a 14-bp sequence was the first polymorphism described and it is the most studied in association between HLA-G and disorders.
METHODS
In this study, we performed a systematic review and meta-analysis of all association studies published regarding the HLA-G 14-bp.
RESULTS
We verified association between 14-bp alleles and diseases in the following situations: (1) presence of 14-bp (insertion) conferred susceptibility to preeclampsia (child alleles evaluated) and systemic lupus erythematosus (OR = 1.42; 95%CI = 1.04-1.93; p = 0.026 and OR = 1.13; 95%CI = 1.01-1.27, p = 0.028); (2) 14-bp absence (deletion) was associated with increased risk to breast cancer (OR = 1.23; 95%CI = 1.06-1.43; p = 0.006) and human Cytomegalovirus infection (OR = 2.06; 95%CI = 1.60-2.64; p < 0.0001); and (3) a risk association was observed between the group of reproductive disorders and the 14-bp insertion (OR = 1.12; 95%CI = 1.01-1.24; p = 0.034).
CONCLUSIONS
Considering that others 14-bp associations were inconclusive and that other variation sites observed at HLA-G 3'UTR exhibit a proven role on post-transcriptional regulation of HLA-G expression, the complete 3'UTR segment should be analyzed in terms of disease susceptibility, instead of a single polymorphism.
Topics: 3' Untranslated Regions; Alleles; Genetic Association Studies; Genetic Predisposition to Disease; HLA-G Antigens; Humans; INDEL Mutation; Lupus Erythematosus, Systemic; Odds Ratio; Open Reading Frames; Polymorphism, Genetic; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid
PubMed: 30102938
DOI: 10.1016/j.humimm.2018.08.003 -
BJS Open May 2024Diverticulosis is a normal anatomical variant of the colon present in more than 70% of the westernized population over the age of 80. Approximately 3% will develop...
BACKGROUND
Diverticulosis is a normal anatomical variant of the colon present in more than 70% of the westernized population over the age of 80. Approximately 3% will develop diverticulitis in their lifetime. Many patients present emergently, suffer high morbidity rates and require substantial healthcare resources. Diverticulosis is the most common finding at colonoscopy and has the potential for causing a significant morbidity rate and burden on healthcare. There is a need to better understand the aetiology and pathogenesis of diverticular disease. Research suggests a genetic susceptibility of 40-50% in the formation of diverticular disease. The aim of this review is to present the hypothesized functional effects of the identified gene loci and environmental factors.
METHODS
A systematic literature review was performed using PubMed, MEDLINE and Embase. Medical subject headings terms used were: 'diverticular disease, diverticulosis, diverticulitis, genomics, genetics and epigenetics'. A review of grey literature identified environmental factors.
RESULTS
Of 995 articles identified, 59 articles met the inclusion criteria. Age, obesity and smoking are strongly associated environmental risk factors. Intrinsic factors of the colonic wall are associated with the presence of diverticula. Genetic pathways of interest and environmental risk factors were identified. The COLQ, FAM155A, PHGR1, ARHGAP15, S100A10, and TNFSF15 genes are the strongest candidates for further research.
CONCLUSION
There is increasing evidence to support the role of genomics in the spectrum of diverticular disease. Genomic, epigenetic and omic research with demographic context will help improve the understanding and management of this complex disease.
Topics: Humans; Risk Factors; Epigenesis, Genetic; Genetic Predisposition to Disease; Diverticular Diseases; Gene-Environment Interaction; Obesity
PubMed: 38831715
DOI: 10.1093/bjsopen/zrae032 -
PloS One 2016Cervical cancer (CC) has one of the highest mortality rates among women worldwide. Several efforts have been made to identify the genetic susceptibility factors... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Cervical cancer (CC) has one of the highest mortality rates among women worldwide. Several efforts have been made to identify the genetic susceptibility factors underlying CC development. However, only a few polymorphisms have shown consistency among studies.
MATERIALS AND METHODS
We conducted a systematic review of all recent case-control studies focused on the evaluation of single nucleotide polymorphisms (SNPs) and CC risk, stringently following the "PRISMA" statement recommendations. The MEDLINE data base was used for the search. A total of 100 case-control studies were included in the meta-analysis. Polymorphisms that had more than two reports were meta-analyzed by fixed or random models according to the heterogeneity presented among studies.
RESULTS
We found significant negative association between the dominant inheritance model of p21 rs1801270 polymorphism (C/A+A/A) and CC (pooled OR = 0.76; 95%CI: 0.63-0.91; p<0.01). We also found a negative association with the rs2048718 BRIP1 polymorphism dominant inheritance model (T/C+C/C) and CC (pooled OR = 0.83; 95%CI: 0.70-0.98; p = 0.03), as well as with the rs11079454 BRIP1 polymorphism recessive inheritance model and CC (pooled OR = 0.79; 95%CI: 0.63-0.99; p = 0.04). Interestingly, we observed a strong tendency of the meta-analyzed studies to be of Asiatic origin (67%). We also found a significant low representation of African populations (4%).
CONCLUSIONS
Our results provide evidence of the negative association of p21 rs1801270 polymorphism, as well as BRIP1 rs2048718 and rs11079454 polymorphisms, with CC risk. This study suggests the urgent need for more replication studies focused on GWAS identified CC susceptibility variants, in order to reveal the most informative genetic susceptibility markers for CC across different populations.
Topics: Alleles; Female; Genetic Predisposition to Disease; Humans; Models, Genetic; Polymorphism, Single Nucleotide; Uterine Cervical Neoplasms
PubMed: 27415837
DOI: 10.1371/journal.pone.0157344