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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 -
Environmental Health : a Global Access... Jun 2017Evidence shows that both the physical and social environments play a role in the development of cardiovascular disease. The purpose of this systematic review is... (Review)
Review
BACKGROUND AND METHODS
Evidence shows that both the physical and social environments play a role in the development of cardiovascular disease. The purpose of this systematic review is two-fold: First, we summarize research from the past 12 years from the growing number of studies focused on effect modification of the relationships between air pollution and cardiovascular disease (CVD) outcomes by socioeconomic position (SEP) and; second, we identify research gaps throughout the published literature on this topic and opportunities for addressing these gaps in future study designs.
RESULTS
We identified 30 articles that examined the modifying effects of either material resources or psychosocial stress (both related to SEP) on associations between short and long-term air pollution exposure and CVD endpoints. Although 18 articles identified at least one interaction between an air pollutant and material resource indicator, 11 others did not. Support for susceptibility to air pollution by psychosocial stress was weaker; however, only three articles tested this hypothesis. Further studies are warranted to investigate how air pollution and SEP together may influence CVD.
CONCLUSIONS
We recommend that such research include thorough assessment of air pollution and SEP correlations, including spatial correlation; investigate air pollution indices or multi-pollutant models; use standardized metrics of SEP to enhance comparability across studies; and evaluate potentially susceptible populations.
Topics: Air Pollutants; Air Pollution; Cardiovascular Diseases; Disease Susceptibility; Environmental Exposure; Prevalence; Social Class; Stress, Physiological
PubMed: 28615066
DOI: 10.1186/s12940-017-0270-0 -
BMC Endocrine Disorders Sep 2023The effect of stress on Graves' disease (GD) is controversial. Our purpose was to quantify the impacts of stress on patients with Graves' disease. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effect of stress on Graves' disease (GD) is controversial. Our purpose was to quantify the impacts of stress on patients with Graves' disease.
METHODS
Systematic searches of PubMed, MEDLINE, Embase, Web of Science, Scopus, Cochrane Library and PsycInfo were conducted from inception to 1 January 2023. Studies comparing the incidence of stressful life events (SLEs) that occurred before diagnosis and during drug therapy in cases diagnosed with GD and controls were included in the final analysis.
RESULTS
Nine case-control studies and four cohort studies enrolling 2892 participants (1685 [58%] patients) were included. Meta-analysis revealed a high and significant effect-size index in a random effect model (d = 1.81, P = 0.01), indicating that stress is an important factor in the onset of GD. The relationship between SLEs and GD was stronger in studies with higher proportions of female patients (β = 0.22, P < 0.01) and weaker in studies with older patients with GD (β =-0.62, P < 0.01). However, stress did not significantly affect the outcome of antithyroid drug therapy for GD (d = 0.32, P = 0.09).
CONCLUSIONS
The results of this meta-analysis suggest that stress is one of the environmental triggers for the onset of GD. Therefore, we recommend stress management assistance for individuals genetically susceptible to GD, especially for young females.
Topics: Humans; Female; Graves Disease; Antithyroid Agents; Case-Control Studies; Genetic Predisposition to Disease
PubMed: 37700292
DOI: 10.1186/s12902-023-01450-y -
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 -
Frontiers in Immunology 2021Myasthenia gravis (MG) is an autoimmune disease primarily mediated by acetylcholine receptor antibodies (AChR-Ab), cellular immune dependence, and complement system... (Review)
Review
Myasthenia gravis (MG) is an autoimmune disease primarily mediated by acetylcholine receptor antibodies (AChR-Ab), cellular immune dependence, and complement system involvement. Since the AChR on the postsynaptic membrane is destroyed by an immune attack, sufficient endplate potential cannot be generated, resulting in the development of a synaptic transmission disorder at the neuromuscular junction and in muscle weakness. The role of the complement system in MG has been demonstrated in animal models and clinical tests, and it has been determined that complement inhibition in patients with MG can prevent disease induction and reverse its progression. Eculizumab is a humanized monoclonal antibody that inhibits the cleavage of complement protein C5 and prevents autoimmune damage; additionally, it has received subsequent approval by the Federal Drug Administration of the United States for MG treatment. However, various concerns regarding the use of eculizumab persist. In this review, we have discussed the treatment time, cost effectiveness, long-term efficacy, and tolerability of eculizumab for MG treatment. We have also summarized historical information and have presented perspectives on this new therapeutic modality.
Topics: Animals; Antibodies, Monoclonal, Humanized; Clinical Trials as Topic; Combined Modality Therapy; Complement Inactivating Agents; Complement System Proteins; Disease Management; Disease Susceptibility; Drug Development; Humans; Myasthenia Gravis; Treatment Outcome
PubMed: 34456922
DOI: 10.3389/fimmu.2021.715036 -
Journal of Autoimmunity Sep 2017With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs.... (Review)
Review
With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated. The non-HLA genes associated with SSc are involved in various functions, with the most robust associations including genes for B and T cell activation and innate immunity. Other pathways include genes involved in extracellular matrix deposition, cytokines, and autophagy. Among these genes, IRF5, STAT4, and CD247 were replicated most frequently while SNPs rs35677470 in DNASE1L3, rs5029939 in TNFAIP3, and rs7574685 in STAT4 have the strongest associations with SSc. In addition to genetic predisposition, it became clear that environmental factors and epigenetic influences also contribute to the development of SSc. Epigenetics, which refers to studies that focus on heritable phenotypes resulting from changes in chromatin structure without affecting the DNA sequence, is one of the most rapidly expanding fields in biomedical research. Indeed extensive epigenetic changes have been described in SSc. Alteration in enzymes and mediators involved in DNA methylation and histone modification, as well as dysregulated non-coding RNA levels all contribute to fibrosis, immune dysregulation, and impaired angiogenesis in this disease. Genes that are affected by epigenetic dysregulation include ones involved in autoimmunity, T cell function and regulation, TGFβ pathway, Wnt pathway, extracellular matrix, and transcription factors governing fibrosis and angiogenesis. In this review, we provide a comprehensive overview of the current findings of SSc genetic susceptibility, followed by an extensive description and a systematic review of epigenetic research that has been carried out to date in SSc. We also summarize the therapeutic potential of drugs that affect epigenetic mechanisms, and outline the future prospective of genomics and epigenomics research in SSc.
Topics: Epigenomics; Gene-Environment Interaction; Genetic Predisposition to Disease; Genomics; HLA Antigens; Humans; Interferon Regulatory Factors; Polymorphism, Genetic; STAT4 Transcription Factor; Scleroderma, Systemic; Signal Transduction; Transforming Growth Factor beta
PubMed: 28526340
DOI: 10.1016/j.jaut.2017.05.004 -
PloS One 2015To evaluate the association between the EPHX1 Tyr113His and His139Arg polymorphisms in the EPHX1 gene and the risk of head and neck cancer. (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the association between the EPHX1 Tyr113His and His139Arg polymorphisms in the EPHX1 gene and the risk of head and neck cancer.
MATERIALS AND METHODS
Studies on the association of EPHX1 Tyr113His and His139Arg polymorphisms with HNC performed up until June 1st, 2014, were identified using a predefined search strategy. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of these associations.
RESULTS
In this meta-analysis, 10 case-control studies, which included 9 studies of Tyr113His (1890 cases and 1894 controls) and 10 studies of His139Arg polymorphisms (1982 cases and 2024 controls), were considered eligible for inclusion. Overall, the pooled results indicated that the EPHX1 Tyr113His polymorphism was significantly associated with increased HNC risk (Tyr/His vs. Tyr/Tyr, OR = 1.26, 95%1.02-1.57;His/His+ Tyr/His vs. Tyr/Tyr, OR = 1.29, 95% I = 1.03-1.61). However, no significant association was found between the His139Arg polymorphism and HNC risk. In the subgroup analysis, a statistically significant association between the EPHX1 Tyr113His polymorphism and HNC was observed in population-based case-control studies (PCC), which involved less than 500 participants and genotype frequencies in HWE. This association showed minimal heterogeneity after excluding studies that were determined to contribute to heterogeneity. After categorizing the studies by publication time, a sensitivity analysis and cumulative meta-analysis of the two associations were conducted, and the results of the two analyses were consistent.
CONCLUSION
Our meta-analysis suggests that EPHX1 Tyr113His polymorphism may be a risk factor for HNC, while the EPHX1 His139Arg polymorphism has no association with HNC risk.
Topics: Epoxide Hydrolases; Genetic Predisposition to Disease; Head and Neck Neoplasms; Humans; Polymorphism, Genetic; Risk Factors
PubMed: 25923690
DOI: 10.1371/journal.pone.0123347 -
European Journal of Medical Research Feb 2022To determine the effect of polymorphisms and mutations in angiotensin-converting enzyme 2 (ACE2) and Type 2 transmembrane serine proteases (TMPRSS2) genes on...
OBJECTIVE
To determine the effect of polymorphisms and mutations in angiotensin-converting enzyme 2 (ACE2) and Type 2 transmembrane serine proteases (TMPRSS2) genes on susceptibility to corona virus disease 2019 (COVID-19) and patient prognosis.
INTRODUCTION
From December 2019 to the current time, an outbreak of epidemic of COVID-19, characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occurred around the world. It is now clear that SARS-CoV-2 binds to human ACE2 receptors, with expression of these receptors correlated with the rate of SARS-CoV-2 infection and mortality. Polymorphisms in individual patient factors, such as ACE2 and TMPRSS2 genes have been linked with an increase in negative outcomes, although evidence to affirm remains debatable.
METHODS
Here, we performed a systematic review, based on guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, with the aim of assessing whether polymorphisms in ACE2 and TMPRSS2 genes affect the COVID-19 condition. We extensively searched PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science databases, for relevant articles and reports published in English between December 2019 and December 2021.
RESULTS
A total of 495 full-text articles were downloaded, of which 185 were excluded after preliminary examination as they were duplicates. Finally, 310 articles were evaluated, by reading their titles and abstracts, and 208 of them eliminated based on our selection criteria. Finally, 33 articles met our inclusion criteria and were included in the final assessment. Genetic data from 33,923 patients with COVID-19 drawn from the general population and deriving from over 160 regions and 50 countries, as well as approximately 560,000 samples from global-public genetic databases, were included in our analysis. Ultimately, we identified 10 SNPs and 21 mutations in the ACE2 gene, along with 13 SNPs and 12 variants in the TMPRSS2 gene, which may be associated with COVID-19.
CONCLUSIONS
ACE2 and TMPRSS2 play vital roles in the onset, development, and prognosis of SARS-CoV-2 infection, and have both been strongly associated with vulnerability, intensity, and the clinical result of COVID-19. Overall, these genetic factors may have potential for future development of personalized drugs and vaccines against COVID-19.
TRIAL REGISTRATION
CRD42021239400 in PROSPERO 2021.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Genetic Predisposition to Disease; Humans; Mutation; Polymorphism, Single Nucleotide; SARS-CoV-2; Serine Endopeptidases
PubMed: 35193695
DOI: 10.1186/s40001-022-00647-6 -
Association between the XRCC6 polymorphisms and cancer risks: a systematic review and meta-analysis.Medicine Jan 2015A number of studies have been carried out to investigate the association of X-ray repair complementing defective repair in Chinese hamster cells 6 (XRCC6) polymorphisms... (Meta-Analysis)
Meta-Analysis Review
A number of studies have been carried out to investigate the association of X-ray repair complementing defective repair in Chinese hamster cells 6 (XRCC6) polymorphisms and cancer risks, and the results remained inconsistent and inconclusive.To assess the effect of XRCC6 polymorphisms on cancer susceptibility, we conducted a meta-analysis, up to May 23rd 2014, 6267 cases with different types of tumor and 7536 controls from 20 published case-control studies. Summary odds ratios and corresponding 95% confidence intervals for XRCC6 polymorphism and cancer risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses, logistic meta-regression analyses and Galbraith plot. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed.The rs2267437 polymorphism was associated with a significant increase in risks of overall cancers, breast cancer, renal cell carcinoma and hepatocellular carcinoma, and it could increase the cancer risk in Asian population; the rs5751129 polymorphism could increase the cancer risk in overall cancers; the rs132770 polymorphism was associated with the increased renal cell carcinoma risk; furthermore, the rs132793 polymorphism could decrease breast cancer risk and increase risks in "other cancers".Overall, the results provided evidences that the single nucleotide polymorphisms in XRCC6 promoter region might play different roles in various cancers, indicating different cancers have different tumorigenesis mechanisms. Our studies may perhaps supplement for the disease monitoring of cancers in the future, and additional studies to determine the exact molecular mechanism might provide us with interventions to protect the susceptible subgroups.
Topics: Animals; Antigens, Nuclear; Case-Control Studies; DNA-Binding Proteins; Genetic Heterogeneity; Genetic Predisposition to Disease; Humans; Ku Autoantigen; Neoplasms
PubMed: 25569644
DOI: 10.1097/MD.0000000000000283 -
BMC Medicine Jul 2023Studies of women of European ancestry have shown that the average familial relative risk for first-degree relatives of women with breast cancer is approximately twofold,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies of women of European ancestry have shown that the average familial relative risk for first-degree relatives of women with breast cancer is approximately twofold, but little is known for Asian women. We aimed to provide evidence for the association between family history and breast cancer risk for Asian women by systematically reviewing published literature.
METHODS
Studies reporting the familial relative risk of breast cancer for Asian women were searched in three online databases and complemented by a manual search. Odds ratios (ORs) for the association between family history and breast cancer risk were pooled across all included studies and by subgroups in terms of the type of family history, age, menopausal status and geographical region.
RESULTS
The pooled OR for women who have a first-degree relative with breast cancer was 2.46 (95% confidence interval [CI]: 2.03, 2.97). There was no evidence that the familial risk differed by the type of affected relative (mother versus sisters), the woman's age (< 50 years versus ≥ 50 years), menopausal status (pre versus post) and geographical region (East and Southeast Asia versus other regions) (all P > 0.3). The pooled ORs for women of Asian ancestry with a family history in any relative were similar for those living in non-Asian countries (2.26, 95% CI: 1.42, 3.59) compared with those living in Asian countries (2.18, 95% CI: 1.85, 2.58).
CONCLUSIONS
Family history of breast cancer is associated with an approximately twofold relative risk of breast cancer for Asian women, which is of similar magnitude to that observed for women of European ancestry. This implies that similar familial factors are implicated in breast cancer risk between women of European and Asian ancestries. Genetic factors are likely to play a substantial role in explaining the breast cancer familial risk for Asian women, as similar risks were observed across different living environments and cultures.
Topics: Female; Humans; Middle Aged; Breast Neoplasms; Risk Factors; Genetic Predisposition to Disease; Asia; Mothers; Case-Control Studies
PubMed: 37400822
DOI: 10.1186/s12916-023-02950-3