Candidate Genes Associated with Susceptibility for SARS-Coronavirus

Hsieh, Ying‐Hen; Chen, Cathy W. S.; Schmitz, Shu‐Fang Hsu; King, Chwan-Chuen; Chen, Wei‐Ju; Wu, Yi-Chun; Ho, Mei‐Shang

doi:10.1007/s11538-009-9440-8

Cited by 27 publications

(26 citation statements)

References 19 publications

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“…A single SARS study envisioned a broader role for genetic screening. 37 This study, which genotyped 100 laboratoryconfirmed SARS patients from the Chinese Han population in Taiwan, suggested that during a crisis, genetic screening could not only be helpful for identifying highly susceptible (high-risk) individuals for prevention efforts, but would also be useful for making staffing assignments, with the rationale that healthcare workers who were resistant to infection would be more suited to providing care. 38 Taiwan has genetic discrimination legislation, but many exceptions limit its scope, raising legal questions about whether genetic screening during an infectious disease crisis is permissible.…”

Section: Applicationsmentioning

confidence: 98%

Genomics and High-Consequence Infectious Diseases: A Scoping Review of Emerging Science and Potential Ethical Issues

Boyce

Garibaldi

2019

Health Security

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Host genomic research on high-consequence infectious diseases is a growing area, but the ethical, legal, and social implications of such findings related to potential applications of the research have not yet been identified. While there is a robust ethical debate about the ethical, legal, and social implications of research during an emergency, there has been less consideration of issues facing research conducted outside of the scope of emergency response. Addressing the implications of research at an early stage (anticipatory ethics) helps define the issue space, facilitates preparedness, and promotes ethically and socially responsible practices. To lay the groundwork for more comprehensive anticipatory ethics work, this article provides a preliminary assessment of the state of the field with a scoping review of host genomic research on a subset of highconsequence infectious diseases of relevance to high-level isolation units, focusing on its ethically relevant features and identifying several ethical, legal, and social implications raised by the literature. We discuss the challenges of genomic studies of low-frequency, high-risk events and applications of the science, including identifying targets to guide the development of new therapeutics, improving vaccine development, finding biomarkers to predict disease outcome, and guiding decisions about repurposing existing drugs and genetic screening. Some ethical, legal, and social implications identified in the literature included the rise of systems biology and paradigm shifts in medical countermeasure development; controversies over repurposing of existing drugs; genetic privacy and discrimination; and benefit-sharing and global inequity as part of the broader ecosystem surrounding high-level isolation units. Future anticipatory ethics work should forecast the science and its applications; identify a more comprehensive list of ethical, legal, and social implications; and facilitate evaluation by multiple stakeholders to inform the integration of ethical concerns into high-level isolation unit policy and practice.A key potential benefit of research on the genomics of the host response to infectious diseases is the discovery of new targets for the development of therapies. A paradigm example is the CCR5 delta-32 allele, which confers resistance to HIV-1 in approximately 10% of in-dividuals living in Europe and western Asia. 1 Its discovery launched research to develop therapeutics and vaccines targeting the CCR5 co-receptor. 2 Identifying pathways to new therapeutics, and other medical countermeasures like vaccines, is a central aim of a recent large-scale (8,000-

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Section: Applicationsmentioning

confidence: 98%

Genomics and High-Consequence Infectious Diseases: A Scoping Review of Emerging Science and Potential Ethical Issues

Boyce

Garibaldi

2019

Health Security

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“…A homozygous mutation (dbSNP ID: rs2075761; JSNP ID: IMS-JST003521) at the amino acid position 53 (FGL2 G53E) appears to be weakly associated with level of nasopharyngeal shedding of SARS-CoV ( P = 0.041) [45] . Subsequent studies from the same group confirmed that FGL2 G53E was a dominant risk variant for SARS-CoV infection [46] . Individuals carrying this mutation had about 40% higher SARS-infection rate than those without this mutation ( P < 0.0001) [46] .…”

Section: Pathogenesismentioning

confidence: 99%

“…Subsequent studies from the same group confirmed that FGL2 G53E was a dominant risk variant for SARS-CoV infection [46] . Individuals carrying this mutation had about 40% higher SARS-infection rate than those without this mutation ( P < 0.0001) [46] .…”

Section: Pathogenesismentioning

confidence: 99%

Physiological functions and clinical implications of fibrinogen-like 2: A review

Yang

Hooper

2013

WJCID

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Fibrinogen-like 2 (FGL2) encompasses a transmembrane (mFGL2) and a soluble (sFGL2) form with differential tertiary structure and biological activities. Typically, mFGL2 functions as prothrombinase that is capable of initiating coagulation in tissue without activation of the blood clotting cascade, whereas sFGL2 largely acts as an immunosuppressor that can repress proliferation of alloreactive T lymphocytes and maturation of bone marrow dendritic cells. Protein sequences of FGL2 exhibit evolutionary conservation across wide variety of species, especially at the carboxyl terminus that contains fibrinogen related domain (FRED). The FRED of FGL2 confers specificity and complexity in the action of FGL2, including receptor recognition, calcium affiliation, and substrate binding. Constitutive expression of FGL2 during embryogenesis and in mature tissues suggests FGL2 might be physiologically important. However, excessive induction of FGL2 under certain medical conditions (e.g., pathogen invasion) could trigger complement activation, inflammatory response, cellular apoptosis, and immune dysfunctions. On the other hand, complete absence of FGL2 is also detrimental as lack of FGL2 can cause autoimmune glomerulonephritis and acute cellular rejection of xenografts. All these roles involve mFGL2, sFGL2, or their combination. Although it is not clear how mFGL2 is cleaved off its host cells and secreted into the blood, circulating sFGL2 has been found correlated with disease severity and viral loading among patients with human hepatitis B virus or hepatitis C virus infection. Further studies are warranted to understand how FGL2 expression is regulated under physiological and pathological conditions. Even more interesting is to determine whether mFGL2 can fulfill an immunoregulatory role through its FRED at carboxyl end of the molecule and, and vice versa, whether sFGL2 is procoagulant upon binding to a target cell. Knowledge in this area should shed light on development of sFGL2 as an alternative immunosuppressive agent for organ transplantation or as a biomarker for predicting disease progression, monitoring therapeutic effects, and targeting FGL2 for repression in ameliorating fulminant viral hepatitis.

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“…CD8 + and CD4 + T cells constitutively secrete FGL2 protein to induce an inflammatory response. Several disorders, including severe acute respiratory syndrome (SARS), abortion and allograft rejection, are correlated with FGL2 (Hsieh et al, 2010;Zhao et al, 2013). In the area of cancer research, previous studies have found that altered FGL2 gene expression contributes to immune surveillance evasion in murine renal carcinoma (Birkhäuser et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

FGL2 is positively correlated with enhanced antitumor responses mediated by T cells in lung adenocarcinoma

Yuan

Feng

Wang

et al. 2020

PeerJ

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Lung cancer is the most common malignant tumor, accounting for 25% of cancerrelated deaths and 14% of new cancers worldwide. Lung adenocarcinoma is the most common type of pulmonary cancer. Although there have been some improvements in the traditional therapy of lung cancer, the outcome and prognosis of patients remain poor. Lung cancer is the leading cause of cancer-related deaths worldwide, with 1.8 million new cases being diagnosed each year. Precision medicine based on genetic alterations is considered a new strategy of lung cancer treatment that requires highly specific biomarkers for precision diagnosis and treatment. Fibrinogen-like protein 2 (FGL2) plays important roles in both innate and adaptive immunity. However, the diagnostic value of FGL2 in lung cancer is largely unknown. In this study, we systematically investigated the expression profile and potential functions of FGL2 in lung adenocarcinoma. We used the TCGA and Oncomine datasets to compare the FGL2 expression levels between lung adenocarcinoma and adjacent normal tissues. We utilized the GEPIA, PrognoScan and Kaplan-Meier plotter databases to analyze the relationship between FGL2 expression and the survival of lung adenocarcinoma patients. Then, we investigated the potential roles of FGL2 in lung adenocarcinoma with the TIMER database and functional enrichment analyses. We found that FGL2 expression was significantly lower in lung adenocarcinoma tissue compared with adjacent normal tissue. A high expression level of FGL2 was correlated with better prognostic outcomes of lung adenocarcinoma patients, including overall survival and progression-free survival. FGL2 was positively correlated with the infiltration of immune cells, including dendritic cells, CD8 + T cells, macrophages, B cells, and CD4 + T cells, in lung adenocarcinoma. Functional enrichment analyses also showed that a high expression level of FGL2 was positively correlated with enhanced T cell activities, especially CD8 + T cell activation. Thus, we propose that high FGL2 expression, which is positively associated with enhanced antitumor activities mediated by T cells, is a beneficial marker for lung adenocarcinoma treatment outcomes. . 2020. FGL2 is positively correlated with enhanced antitumor responses mediated by T cells in lung adenocarcinoma. PeerJ 8:e8654 http://doi.BE, Golub TR, Sugarbaker DJ, Meyerson M. 2001. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Said JW, McBride WH, Kabbinavar FF, Ribas A, Pantuck AJ, Belldegrun AS, Riss J. 2013. Dendritic cell-based immunotherapy in prevention and treatment of renal cell carcinoma: efficacy, safety, and activity of Ad-GM·CAIX in immunocompetent mouse models. Journal T. 2013. Soluble FGL2 induced by tumor necrosis factor-α and interferon-γ in CD4+ T cells through MAPK pathway in human renal allograft acute rejection.

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Candidate Genes Associated with Susceptibility for SARS-Coronavirus

Cited by 27 publications

References 19 publications

Genomics and High-Consequence Infectious Diseases: A Scoping Review of Emerging Science and Potential Ethical Issues

Genomics and High-Consequence Infectious Diseases: A Scoping Review of Emerging Science and Potential Ethical Issues

Physiological functions and clinical implications of fibrinogen-like 2: A review

FGL2 is positively correlated with enhanced antitumor responses mediated by T cells in lung adenocarcinoma

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